2022/05/26 更新

写真a

コンドウ ヨシタカ
近藤 嘉高
所属
人間科学学術院 人間科学部
職名
講師(任期付)
ホームページ

学歴

  • 2004年04月
    -
    2007年03月

    東京医科歯科大学   大学院博士課程   医歯学総合研究科血流制御内科学専攻  

  • 2002年04月
    -
    2004年03月

    東京医科歯科大学   大学院修士課程   医歯学総合研究科血流制御内科学専攻  

  • 1998年04月
    -
    2002年03月

    早稲田大学   教育学部   理学科 生物学専修  

学位

  • 東京医科歯科大学   博士(医学)

経歴

  • 2019年04月
    -
    継続中

    早稲田大学   人間科学学術院   講師(任期付)

  • 2016年04月
    -
    2019年03月

    地方独立行政法人東京都健康長寿医療センター 東京都健康長寿医療センター研究所   老化制御研究チーム 分子老化制御   研究員

  • 2014年04月
    -
    2016年03月

    東邦大学   理学部 生物分子科学科 生物医学部門   博士研究員

  • 2009年04月
    -
    2014年03月

    地方独立行政法人東京都健康長寿医療センター   東京都健康長寿医療センター研究所   研究員

  • 2008年04月
    -
    2009年03月

    東京都老人総合研究所   研究員

  • 2007年04月
    -
    2008年03月

    独立行政法人日本学術振興会   特別研究員PD

  • 2006年04月
    -
    2007年03月

    独立行政法人日本学術振興会   特別研究員DC2

  • 2016年04月
    -
    2020年03月

    東京農工大学   大学院農学府   非常勤講師

  • 2018年04月
    -
    2019年03月

    早稲田大学   人間科学部   非常勤講師

  • 2014年04月
    -
    2016年03月

    東邦大学   大学院理学研究科   非常勤講師

  • 2014年04月
    -
    2015年03月

    東邦大学   理学部   非常勤講師

  • 2008年04月
    -
    2009年03月

    東邦大学   大学院薬学研究科   客員講師

  • 2007年04月
    -
    2008年03月

    東京都老人総合研究所   協力研究員

  • 2002年04月
    -
    2007年03月

    東京都老人総合研究所   研究生

  • 2005年04月
    -
    2006年03月

    東京医科歯科大学   大学院医歯学総合研究科   リサーチアシスタント

▼全件表示

所属学協会

  • 2015年06月
    -
    継続中

    日本老年医学会

  • 2014年09月
    -
    継続中

    日本免疫学会

  • 2013年08月
    -
    継続中

    日本分子生物学会

  • 2008年07月
    -
    継続中

    日本未病システム学会

  • 2007年02月
    -
    継続中

    日本栄養・食糧学会

  • 2007年02月
    -
    継続中

    日本ビタミン学会

  • 2003年10月
    -
    継続中

    日本生化学会

  • 2002年03月
    -
    継続中

    日本基礎老化学会

▼全件表示

 

研究分野

  • 分子生物学

  • 実験病理学

  • 代謝、内分泌学

  • 機能生物化学

  • 薬系衛生、生物化学

  • 栄養学、健康科学

  • 食品科学

▼全件表示

研究キーワード

  • カロリー制限

  • 健康長寿

  • 栄養

  • ノックアウトマウス

  • SMP30

  • GNL

  • 水素水

  • NAFLD

  • NASH

  • グルコン酸キナーゼ

  • ペントースリン酸経路

  • 寿命

  • 機能性食品

  • 抗老化

  • 抗酸化

  • グルコノラクトナーゼ

  • 加齢指標タンパク質30

  • 活性酸素種

  • 酸化ストレス

  • SMP30/GNL

  • 加齢

  • アスコルビン酸

  • ビタミンC

  • 老化

▼全件表示

論文

  • Author Correction: Ascorbic acid during the suckling period is required for proper DNA demethylation in the liver.

    Kenichi Kawahori, Yoshitaka Kondo, Xunmei Yuan, Yuki Kawasaki, Nozomi Hanzawa, Kazutaka Tsujimoto, Fumiko Wada, Takashi Kohda, Akihito Ishigami, Tetsuya Yamada, Yoshihiro Ogawa, Koshi Hashimoto

    Scientific reports   11 ( 1 ) 12184 - 12184  2021年06月  [国際誌]

    DOI PubMed

  • Ascorbic acid during the suckling period is required for proper DNA demethylation in the liver.

    Kenichi Kawahori, Yoshitaka Kondo, Xunmei Yuan, Yuki Kawasaki, Nozomi Hanzawa, Kazutaka Tsujimoto, Fumiko Wada, Takashi Kohda, Akihito Ishigami, Tetsuya Yamada, Yoshihiro Ogawa, Koshi Hashimoto

    Scientific reports   10 ( 1 ) 21228 - 21228  2020年12月  [査読有り]  [国際誌]

     概要を見る

    Ascorbic acid (AA, vitamin C) serves as a cofactor for ten-eleven translocation (TET) enzymes and induces DNA demethylation in vitro. However, its role in DNA demethylation in vivo remains unclear. We previously reported that DNA demethylation in the mouse liver was enhanced during the suckling period. Therefore, we hypothesized that DNA demethylation is enhanced in an AA-dependent manner during the suckling period. To examine our hypothesis, we employed wild-type (WT) mice, which synthesize AA, and senescence marker protein-30/gluconolactonase (SMP30/GNL) knockout (KO) mice, which cannot synthesize AA, and analyzed the DNA methylation status in the livers of offspring in both the suckling period and adulthood. SMP30/GNL KO offspring showed DNA hypermethylation in the liver possibly due to low plasma and hepatic AA levels during the suckling period despite the administration of rescue-dose AA to dams. Furthermore, DNA hypermethylation of the fibroblast growth factor 21 gene (Fgf21), a PPARα target gene, persisted into adulthood. In contrast, a high-dose AA administration to SMP30/GNL KO dams during the lactation period restored DNA demethylation in the livers of offspring. Even though a slight increase was observed in plasma AA levels with the administration of rescue-dose AA to WT dams during the gestation and lactation periods, DNA demethylation in the livers of offspring was minimally enhanced. The present results demonstrate that AA intake during the suckling period is required for proper DNA demethylation in the liver.

    DOI PubMed

  • Radiation-induced gastrointestinal syndrome is exacerbated in vitamin C-insufficient SMP30/GNL knockout mice.

    Reina Saga, Takahiro Uchida, Yuka Takino, Yoshitaka Kondo, Hiroaki Kobayashi, Manabu Kinoshita, Daizoh Saitoh, Akihito Ishigami, Makoto Makishima

    Nutrition (Burbank, Los Angeles County, Calif.)   81   110931 - 110931  2020年07月  [査読有り]  [国際誌]

     概要を見る

    OBJECTIVES: Accidental exposure to high-dose radiation causes life-threatening acute radiation syndrome, features that include gastrointestinal syndrome (GIS) and hematopoietic syndrome (HS). Administration of vitamin C (VC), a free radical scavenger, has been reported to increase survival of mice in GIS and HS models. The effect of nutritional VC status on radiation injury remains unknown because, unlike humans, mice can synthesize VC. The aim of this study was to investigate the effect of VC insufficiency on acute radiation syndrome using senescence marker protein 30 (SMP30)/gluconolactonase knockout (SMP30-KO) mice. METHODS: SMP30-KO mice, which cannot synthesize VC, were given water with or without sufficient VC supplementation, and were analyzed in GIS and HS models. RESULTS: In the GIS model, in which bone marrow failure is rescued by bone marrow transplantation, VC-insufficient mice had a lower survival rate than VC-sufficient mice. The intestine of VC-insufficient GIS mice showed epithelial cell atrophy, inflammatory cell infiltration, and decreased crypt cell proliferation. We observed rapid VC oxidation after total body irradiation in the intestine of mice supplemented with VC-sufficient water. In the HS model, which was not combined with bone marrow transplantation, there was no difference in survival between VC-insufficient and -sufficient mice. CONCLUSION: The results of this study demonstrated that nutritionally sufficient VC exerts a radioprotective effect against radiation-induced GIS.

    DOI PubMed

  • Decreased ADAM17 expression in the lungs of α-Klotho reduced mouse.

    Keiko Akasaka-Manya, Hiroshi Manya, Satomi Nadanaka, Hiroshi Kitagawa, Yoshitaka Kondo, Akihito Ishigami, Tamao Endo

    Journal of biochemistry   167 ( 5 ) 483 - 493  2020年05月  [査読有り]  [国際誌]

     概要を見る

    The deficiency of α-Klotho in mice causes phenotypes resembling human age-associated disorders at 3-4 weeks after birth and shows short lifespans of ∼2 months. One of the crucial symptoms is pulmonary emphysema, although α-Klotho is not expressed in the lungs. α-Klotho secreted from the kidneys is probably involved in the pathology of emphysema because kidney-specific knockout mice exhibit emphysematous structural changes. We examined whether any glycan changes in α-Klotho mouse lungs were observed, because α-Klotho is reported to have glycosidase activity. Here, we found the accumulation of heparan sulphate in the microsomal fraction of α-Klotho mouse lungs. Meanwhile, a disintegrin and metalloproteinase 17 (ADAM17) expression was decreased in α-Klotho mice. From these results, it is thought that the increase in heparan sulphate is due to insufficient cleavage of the core protein by ADAM17. Additionally, a reduction in α-Klotho and a decline of ADAM17 were also observed both in normal aged mice and in senescence marker protein-30 (SMP30) knockout mice, a mouse model of premature ageing. Thus, the decrease in ADAM17 is caused by the reduction in α-Klotho. These may be involved in the deterioration of lung function during ageing and may be associated with the pathology of pulmonary emphysema.

    DOI PubMed

  • Effects of rikkunshito supplementation on resistance to oxidative stress and lifespan in mice.

    Zi Wang, Toshimitsu Komatsu, Yoshihisa Ohata, Yukari Watanabe, Yiwen Yuan, Yuki Yoshii, Seongjoon Park, Ryoichi Mori, Motoyasu Satou, Yoshitaka Kondo, Isao Shimokawa, Takuya Chiba

    Geriatrics & gerontology international   20 ( 3 ) 238 - 247  2020年03月  [査読有り]  [国内誌]

     概要を見る

    AIM: Caloric restriction (CR), which limits the caloric intake to 60-70% of ad libitum (AL) amounts in various experimental animals, delays aging and extends the lifespan. We previously showed that neuropeptide Y (NPY), an appetite-stimulating peptide, is essential for the anti-oxidative and life-extending effects of CR. Here, we investigated whether a Japanese traditional herbal medicine, rikkunshito (RKT), which induces NPY activation, has CR-like life-extending effects. METHODS: First, we evaluated the life-extending activity of RKT by examining the effect of long-term RKT administration on wild-type and NPY knockout mice. Furthermore, we tested whether RKT enhances CR-mediated beneficial effects under AL conditions with a normal diet and under mild CR conditions with a high-fat diet. We then used 3-nitropropionic acid or doxorubicin to induce oxidative stress, and analyzed the differences in survival rate, weight loss, gene expression and cellular oxidative damage among groups. RESULTS: RKT administration did not extend the lifespan of wild-type or NPY knockout mice. In the oxidative stress models, RKT treatment upregulated anti-oxidative gene expression in the liver. Furthermore, RKT administration reduced the oxidative damage in the liver compared to the CR conditions alone. However, on induction of oxidative stress by 3-nitropropionic acid or doxorubicin, RKT administration did not affect the survival rate. CONCLUSIONS: These results show that RKT administration only partially mimics the effects of CR at the cellular level, but not at the organismal level to increase the lifespan of mice. Geriatr Gerontol Int 2019; ••: ••-••.

    DOI PubMed

  • Acerola (Malpighia emarginata DC.) Promotes Ascorbic Acid Uptake into Human Intestinal Caco-2 Cells via Enhancing the Gene Expression of Sodium-Dependent Vitamin C Transporter 1.

    Yuka Takino, Hitoshi Aoki, Yoshitaka Kondo, Akihito Ishigami

    Journal of nutritional science and vitaminology   66 ( 4 ) 296 - 299  2020年  [査読有り]  [国内誌]

     概要を見る

    Acerola (Malpighia emarginata DC.) is a fruit containing abundant ascorbic acid (AsA) and numerous functional phytochemicals. We previously reported that the intake of acerola juice increased the absorption of AsA in plasma of healthy Japanese subjects. The functional phytochemicals in acerola may influence the intestinal epithelial cells to increase the cellular uptake of AsA. Therefore, in this study, we compared the AsA uptake into Caco-2 cells between AsA alone and that in acerola juice at the same concentration using a human intestinal model. Caco-2 cells were incubated with 3 mM AsA and 3 mM AsA in acerola juice. Intracellular AsA contents gradually increased until 24 h upon incubation with both AsA alone and AsA in acerola juice; however, these contents when incubated with AsA in acerola juice, were significantly higher than those incubated with AsA alone at 2, 3, 4, 8, and 24 h. Furthermore, the mRNA expression level of the sodium-dependent vitamin C transporter (SVCT) 1 was significantly higher in the cells incubated with AsA in acerola juice than those incubated with AsA alone. Moreover, polyphenols such as cyanidin-3-glucoside chloride and quercetin enhanced the SVCT1 gene expression in Caco-2 cells. Collectively, these results suggest that acerola polyphenols enhances the SVCT1 gene expression in Caco-2 cells and promotes AsA uptake.

    DOI PubMed

  • Taurine Improves Lipid Metabolism and Increases Resistance to Oxidative Stress.

    Zi Wang, Yoshihisa Ohata, Yukari Watanabe, Yiwen Yuan, Yuki Yoshii, Yoshitaka Kondo, Shoko Nishizono, Takuya Chiba

    Journal of nutritional science and vitaminology   66 ( 4 ) 347 - 356  2020年  [査読有り]  [国内誌]

     概要を見る

    Calorie restriction (CR) by 30-40% decreases morbidity of age-related diseases and prolongs the lifespan of various laboratory animal species. Taurine (2-aminoethanesulfonic acid) is an important nutrient for lipid metabolism as it conjugates bile acids. Here, we investigated how taurine supplementation induces effects similar to the CR beneficial effects. Sprague Dawley rats were fed a diet containing different taurine concentrations (0, 0.5, 1.0, 3.0, 5.0%) to analyze the effects on growth, blood, and hepatic parameters. Rats fed a 5% taurine-supplemented diet showed a significant decrease in visceral fat weight, compared with control rats. Moreover, there were significant decreases in the serum total cholesterol, hepatic cholesterol and triglyceride concentrations in the taurine-supplemented groups compared with the control group in a dose-dependent manner. These results were associated with decreased mRNA expression of fatty acid synthase, and increased mRNA expression of carnitine palmitoyltransferase 1α. C57BL/6 mice were fed a 5.0% taurine-supplemented diet, and their response to 3-nitropropionic acid-induced oxidative stress was analyzed. The rate of weight loss due to oxidative stress decreased and the survival rate significantly increased in the taurine-supplemented groups compared with the control group. Finally, cells were treated with 100 μM taurine and their resistance to UV-induced oxidative stress was analyzed. We found that the p53-Chk1 pathway was less activated in taurine-treated cells compared with control cells. Furthermore, damage to cells evaluated by oxidative stress indicators revealed a reduction in oxidative damage with taurine treatment. These findings suggest that taurine partially acts as a CR mimetic.

    DOI PubMed

  • Dibutyl phthalate impairs neural progenitor cell proliferation and hippocampal neurogenesis.

    Wonjong Lee, Jung-Hyun Cho, Yujeong Lee, Seulah Lee, Dae Hyun Kim, Sugyeong Ha, Yoshitaka Kondo, Akihito Ishigami, Hae Young Chung, Jaewon Lee

    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association   129   239 - 248  2019年07月  [査読有り]  [国際誌]

     概要を見る

    Dibutyl phthalate (DBP) is commonly used plasticizer and a known endocrine disruptor that can cause birth defects and developmental disorders. Although several studies have reported that DBP has neurotoxic effects on neurite outgrowth and on learning and memory, its neurotoxic effects on neural progenitor cells (NPCs) have not been investigated. The present study was undertaken to determine the effects of DBP on NPCs and hippocampal neurogenesis. At high concentration DBP (500 μM) retarded NPC proliferation without affecting cell viability by arresting the cell cycle at G1 but did not cause cell death. DNA damage was observed by examining p53 expression and by γH2AX staining. DBP-treated cells had elevated ROS levels and exhibited mitochondrial dysfunction, which can cause DNA damage. Adult hippocampal neurogenesis was investigated using BrdU immunohistochemistry in young C57BL/6 mice intraperitoneally administrated with vehicle or DBP (10 or 50 mg/kg) for 2 weeks. DBP administered mice were found to have significantly fewer newly generated neurons in hippocampi, and the Morris water maze test revealed that DBP (50 mg/kg) impaired spatial learning and memory. Taken together, these findings suggest that DBP has harmful effects on NPCs and hippocampal neurogenesis and that DBP exposure could lead to learning and memory dysfunctions.

    DOI PubMed

  • Reduced aqueous humour ascorbic-acid concentration in women with smaller anterior chamber depth.

    Sakae Ito, Toshimi Sairenchi, Takehisa Machida, Yuka Takino, Yoshitaka Kondo, Koichiro Mukai, Gen Kobashi, Akihito Ishigami, Tadashi Senoo

    Scientific reports   9 ( 1 ) 372 - 372  2019年01月  [査読有り]  [国際誌]

     概要を見る

    Short anterior chamber depth (ACD) is considered a risk factor of endothelial-cell loss after phacoemulsification. However, whether it is an independent risk factor or not remains controversial. We investigated the relationship between ascorbic acid (AA) concentrations in the aqueous humour (AqH) and ACD. We analysed 165 AqH samples of 97 patients (42 men and 55 women) who underwent small incision cataract surgery. AqH and plasma AA concentrations were measured using a high-performance liquid chromatography - electrochemical detection method. Patient characteristics were compared between and within the sexes. As a result, age and ACD were significantly correlated with AqH AA concentrations (r = -0.206, P = 0.045; r = 0.339, P < 0.001) only in women. Moreover, plasma AA concentrations were significantly correlated with AqH AA concentrations (r = 0.420, P < 0.001; r = 0.316, P = 0.002) both in men and women. After adjusting for confounding factors (age and plasma AA concentrations), ACD was significantly and positively correlated with AqH AA concentrations (partial.r = 0.275, P = 0.009) only in women. In conclusion, AqH AA concentrations were reduced in women with smaller ACD. This may suggest that women with short ACD could be more susceptible to oxidative damage.

    DOI PubMed

  • Myelin Basic Protein Citrullination, a Hallmark of Central Nervous System Demyelination, Assessed by Novel Monoclonal Antibodies in Prion Diseases.

    Byungki Jang, Yong-Chul Jeon, Hae-Young Shin, Yun-Jung Lee, Hyunji Kim, Yoshitaka Kondo, Akihito Ishigami, Yong-Sun Kim, Eun-Kyoung Choi

    Molecular neurobiology   55 ( 4 ) 3172 - 3184  2018年04月  [査読有り]  [国際誌]

     概要を見る

    Myelin basic protein (MBP) citrullination by peptidylarginine deiminase (PAD) enzymes leads to incomplete protein-lipid bilayer interactions and vulnerability to proteolytic enzymes, resulting in disorganization of the myelin sheath in the central nervous system. Therefore, citrullinated MBP (citMBP) has been suggested as a hallmark of demyelination, but how citMBP is implicated in prion diseases remains unknown. For the first time, we developed mouse monoclonal anti-citMBP IgG1 (clones 1B8, 1H1, and 3C6) and IgM (clone 3G5) antibodies that recognize human citMBP at its R25, R122, and R130 residues and at its C-terminal region (or the corresponding sites in mouse MBP), respectively. Using a biochemical, immunohistochemical, and immunogold-silver staining for electron microscopy techniques, we found that MBP residue R23 (corresponding to human R25) was specifically citrullinated, was stained as intense punctae in the corpus callosum, the striatum, and the cerebellar white matter, and was predominantly localized in disorganized myelin in the brains of scrapie-infected mice. In the brains of Creutzfeldt-Jakob disease (CJD) patients, MBP residues R25, R122, and R130 were markedly citrullinated and were stained as fibrils and punctae. In particular, white matter regions, such as the midbrain and the medulla, exhibited high levels of citMBP compared to other regions. However, the high levels of citMBP were not correlated with PAD2 expression. The clone 3G5 recognized significantly increased expression of the 18.5 kDa and/or 21.5 kDa variants of MBP in prion disease. Our findings suggest that significantly increased levels of citMBP may reflect demyelinating neuropathology, and that these newly developed antibodies may be useful for identifying demyelination.

    DOI PubMed

  • Update on deimination in alzheimer's disease

    Yoshitaka Kondo, Eun Kyoung Choi, Yong Sun Kim, Akihito Ishigami

    Protein Deimination in Human Health and Disease: Second Edition     293 - 315  2017年09月  [査読有り]

    DOI

  • Induction of Peptidylarginine Deiminase 2 and 3 by Dibutyryl cAMP via cAMP-PKA Signaling in Human Astrocytoma U-251MG cells

    Hirofumi Masutomi, Saki Kawashima, Yoshitaka Kondo, Yoshiaki Uchida, Byungki Jang, Eun-Kyoung Choi, Yong-Sun Kim, Kentaro Shimokado, Akihito Ishigami

    JOURNAL OF NEUROSCIENCE RESEARCH   95 ( 7 ) 1503 - 1512  2017年07月  [査読有り]

     概要を見る

    Peptidylarginine deiminases (PADs) are posttranslational modification enzymes that citrullinate (deiminate) protein arginine residues in a calcium-dependent manner, yielding citrulline residues. Enzymatic citrullination abolishes positive charges of native protein molecules, inevitably causing significant alterations in their structure and function. Previously, we reported the abnormal accumulation of citrullinated proteins and an increase of PAD2 content in hippocampi of patients with Alzheimer disease. In this study, we investigated PAD expression by using dibutyryl cAMP (dbcAMP) in human astrocytoma U-251MG cells. Under normal culture conditions, PAD2 and PAD3 mRNA expression is detectable with quantitative PCR in U-251MG cells. The addition of dbcAMP in a dose-dependent manner significantly increased this mRNA expression and protein levels. Moreover, PAD enzyme activity also increased significantly and dose-dependently. Furthermore, the expression of PAD2 and PAD3 mRNA was inhibited by the cAMP-dependent PKA inhibitor KT5720, suggesting that such expression of dbcAMP-induced PAD2 and PAD3 mRNA is mediated by the cAMP-PKA signaling pathway in U-251MG cells. This is the first report to document the PAD2 and PAD3 mRNA expression induced by dbcAMP and to attribute the induction of these genes to mediation by the cAMP-PKA signaling pathway in U-251MG cells. (C) 2016 Wiley Periodicals, Inc.

    DOI

  • Time-Dependent Alterations of Vancomycin-Induced Nephrotoxicity in Mice

    Masaki Takigawa, Hirofumi Masutomi, Yuki Kishimoto, Yoshitomo Shimazaki, Yoshitomo Hamano, Yoshitaka Kondo, Tomio Arai, Jaewon Lee, Toshihiro Ishii, Yoshiko Mori, Akihito Ishigami

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   40 ( 7 ) 975 - 983  2017年07月  [査読有り]

     概要を見る

    Vancomycin hydrochloride (VCM) is a glycopeptide antibiotic that is commonly used against methicillin-resistant, Gram-positive cocci despite the nephrotoxic side effects. VCM-induced nephrotoxicity has been reported in 5-28% of recipient patients. Therefore, renal failure induced by VCM has become an important clinical problem. However, the exceedingly complex mechanism of VCM-induced nephrotoxicity is not fully understood. Therefore, this study was designed to clarify time-dependent alterations of VCM-induced nephrotoxicity in mice as a step toward decreasing the risks of kidney injury associated with VCM therapy. VCM was injected intraperitoneally into mice at a dose of 400 mg/kg body weight at 24-h intervals for 3, 5, 7, and 14 d. At 24 h after the last injection, we examined histopathological alterations of the kidney as well as blood biochemistry. VCM administration resulted in a decrease of body weight and increase of kidney weight. Histological examination revealed renal damage such as dilated proximal tubules with occasional casts and interstitial fibrosis in VCM-treated mice. Furthermore, immunohistochemical staining with anti-CD10 and anti-single-stranded DNA antibodies highlighted damaged renal proximal tubules with marked dilatation as well as numerous apoptotic cells as early as day 4 of VCM-treatment. The severity of symptoms progressed until day 15. These results suggest that VCM-induced renal damage and incipient renal failure begin soon after the start of treatment and progressively worsen. This is the first report describing the time-dependence of VCM-induced nephrotoxicity in mice and depicting a model that clarifies the mechanisms of this tissue damage.

    DOI PubMed

  • Bone degeneration and its recovery in SMP30/GNL-knockout mice

    K. Nishijima, T. Ohno, A. Amano, Y. Kishimoto, Y. Kondo, A. Ishigami, S. Tanaka

    The journal of nutrition, health & aging   21 ( 5 ) 573 - 578  2017年05月  [査読有り]

    DOI

  • Abnormal lipid/lipoprotein metabolism and high plasma testosterone levels in male but not female aromatase-knockout mice

    Akiko Amano, Yoshitaka Kondo, Yoshihiro Noda, Mitsuhiro Ohta, Noriaki Kawanishi, Shuichi Machida, Kazuteru Mitsuhashi, Takafumi Senmaru, Michiaki Fukui, Osamu Takaoka, Taisuke Mori, Jo Kitawaki, Masafumi Ono, Toshiji Saibara, Hiroshi Obayashi, Akihito Ishigami

    ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS   622   47 - 58  2017年05月  [査読有り]

     概要を見る

    Sex steroid hormones, such as estrogen and testosterone, are believed to play important roles in lipid metabolism. To elucidate the effects of estrogen depletion on lipid metabolism in male and female mice, we used aromatase-knockout (ArKO) mice, in which Cyp19 gene disruption prevented estrogen synthesis in vivo. These mice were divided into the following 4 groups: male and female ArKO mice and male and female wild-type (WT) mice. These mice were fed a normal-fat diet (13.6% fat) ad libitum. At 159 days after birth, the mice were tested for liver and plasma lipid content and hepatic hormone receptor and lipid/lipoprotein metabolism-related gene expression. Interestingly, we found that hepatic steatosis was accompanied by markedly elevated plasma testosterone levels in male ArKO mice but not in female ArKO mice. Plasma lipoprotein profiles exhibited concurrent decreases in LDL- and small dense LDL-triglyceride (TG) levels in male ArKO mice. Moreover, male mice, but not female mice, exhibited marked elevations in androgen receptor (AR), sterol regulatory element-binding protein I (SREBP1), and CD36 expression. These results strongly suggest that Cyp19 gene disruption, which induces a sexually dimorphic response and high plasma testosterone levels in male mice, also induces hepatic steatosis. (C) 2017 Elsevier Inc. All rights reserved.

    DOI

  • Vitamin C impacts anxiety-like behavior and stress-induced anorexia relative to social environment in SMP30/GNL knockout mice

    Miwako Koizumi, Yoshitaka Kondo, Ayumi Isaka, Akihito Ishigami, Emiko Suzuki

    NUTRITION RESEARCH   36 ( 12 ) 1379 - 1391  2016年12月  [査読有り]

     概要を見る

    The role of endogenous vitamin C (VC) in emotion and psychiatric measures has long been uncertain. We aimed to investigate how an individual's VC status impacts his or her mental health. Our hypothesis is that body VC levels modulate anxiety, anorexia, and depressive phenotypes under the influence of psychosocial rearing environments and sex. The VC status of senescence marker protein-30/gluconolactonase knockout mice, which lack the ability to synthesize VC, were continuously shifted from adequate (VC+) to depleted (VC) by providing a water with or without VC. Despite weight loss in both sexes, suppressed feeding was specifically seen in males only during the VC phase. Anxiety responses in the novelty-suppressed feeding paradigm were worse during the VC, especially in females. Sensitivity to the forced swim test as determined by the initial latency was significantly shorter in the socially stable animals compared with socially unstable animals during the VC+ condition. The stress coping underlying depressive phenotypes was assessed by immobility duration in a series of forced swim tests. No significant differences were apparent between contrasting VC status. Homeostatic symptoms following stressful behavioral tests consisted of a great loss of appetite during the VC. It should be noted that anorexia is extremely serious for the females. We conclude that endogenous VC status is critical for determining vulnerability to anxiety and anorexia in a sex-specific manner. (C) 2016 Elsevier Inc. All rights reserved.

    DOI PubMed

  • Pharmacological and genetic reappraisals of protease and oxidative stress pathways in a mouse model of obstructive lung diseases

    Tsuyoshi Shuto, Shunsuke Kamei, Hirofumi Nohara, Haruka Fujikawa, Yukihiro Tasaki, Takuya Sugahara, Tomomi Ono, Chizuru Matsumoto, Yuki Sakaguchi, Kasumi Maruta, Ryunosuke Nakashima, Taisei Kawakami, Mary Ann Suico, Yoshitaka Kondo, Akihito Ishigami, Toru Takeo, Ken-ichiro Tanaka, Hiroshi Watanabe, Naomi Nakagata, Kohei Uchimura, Kenichiro Kitamura, Jian-Dong Li, Hirofumi Kai

    SCIENTIFIC REPORTS   6   39305  2016年12月  [査読有り]

     概要を見る

    Protease-antiprotease imbalance and oxidative stress are considered to be major pathophysiological hallmarks of severe obstructive lung diseases including chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), but limited information is available on their direct roles in the regulation of pulmonary phenotypes. Here, we utilized beta ENaC-transgenic (Tg) mice, the previously established mouse model of severe obstructive lung diseases, to produce lower-mortality but pathophysiologically highly useful mouse model by backcrossing the original line with C57/BL6J mice. C57/BL6J-beta ENaC-Tg mice showed higher survival rates and key pulmonary abnormalities of COPD/CF, including mucous hypersecretion, inflammatory and emphysematous phenotypes and pulmonary dysfunction. DNA microarray analysis confirmed that protease-and oxidative stress-dependent pathways are activated in the lung tissue of C57/BL6J-beta ENaC-Tg mice. Treatments of C57/BL6J-beta ENaC-Tg mice with a serine protease inhibitor ONO-3403, a derivative of camostat methylate (CM), but not CM, and with an anti-oxidant N-acetylcystein significantly improved pulmonary emphysema and dysfunction. Moreover, depletion of a murine endogenous antioxidant vitamin C (VC), by genetic disruption of VC-synthesizing enzyme SMP30 in C57/BL6J-beta ENaC-Tg mice, exaggerated pulmonary phenotypes. Thus, these assessments clarified that protease-antiprotease imbalance and oxidative stress are critical pathways that exacerbate the pulmonary phenotypes of C57/BL6J-beta ENaC-Tg mice, consistent with the characteristics of human COPD/CF.

    DOI PubMed

  • Involvement of senescence marker protein-30 in glucose metabolism disorder and non-alcoholic fatty liver disease.

    Kondo Y, Ishigami A

    Geriatrics & gerontology international   16 Suppl 1   4 - 16  2016年03月  [査読有り]

    DOI PubMed

  • 分子機序に基づいた難治性呼吸器疾患治療の新展開 閉塞性肺疾患モデルマウスを用いた肺病態増悪因子の同定とその治療的応用

    首藤 剛, 亀井 竣輔, 坂口 由起, 松本 千鶴, 小野 智美, 菅原 卓哉, 野原 寛文, 藤川 春花, 丸田 かすみ, 中嶋 竜之介, スイコ・メリーアン, 近藤 嘉高, 石神 昭人, 甲斐 広文

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   88回・38回   [3W9 - 3]  2015年12月

  • ビタミンCの欠損は、慢性閉塞性肺疾患モデルマウスにおける呼吸機能低下や肺気腫病態を悪化させる

    首藤 剛, 坂口 由起, 野原 寛文, 亀井 竣輔, 藤川 春花, 近藤 嘉高, Suico Mary Ann, 石神 昭人, 甲斐 広文

    日本薬学会年会要旨集   135年会 ( 3 ) 86 - 86  2015年03月

  • Senescence marker protein-30/gluconolactonase deficiency exacerbates diabetic nephropathy through tubular injury in a mouse model of type 1 diabetes.

    Okada H, Senmaru T, Fukui M, Kondo Y, Ishigami A, Maruyama N, Obayashi H, Yamazaki M, Nakamura N, Hasegawa G

    Journal of diabetes investigation   6 ( 1 ) 35 - 43  2015年01月  [査読有り]  [国内誌]

    DOI PubMed

  • Potato chip intake increases ascorbic acid levels and decreases reactive oxygen species in SMP30/GNL knockout mouse tissues.

    Kondo Y, Sakuma R, Ichisawa M, Ishihara K, Kubo M, Handa S, Mugita H, Maruyama N, Koga H, Ishigami A

    Journal of agricultural and food chemistry   62 ( 38 ) 9286 - 9295  2014年09月  [査読有り]

    DOI PubMed

  • Susceptibility quantitative trait loci for pathogenic leucocytosis in SCG/Kj mice, a spontaneously occurring crescentic glomerulonephritis and vasculitis model

    Y. Hamano, M. Abe, S. Matsuoka, D. Zhang, Y. Kondo, Y. Kagami, A. Ishigami, N. Maruyama, Y. Tsuruta, W. Yumura, K. Suzuki

    Clinical & Experimental Immunology   177 ( 1 ) 353 - 365  2014年07月  [査読有り]

    DOI

  • Senescence marker protein-30/superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis.

    Kondo Y, Masutomi H, Noda Y, Ozawa Y, Takahashi K, Handa S, Maruyama N, Shimizu T, Ishigami A

    FEBS open bio   4   522 - 532  2014年  [査読有り]

    DOI PubMed

  • Lepr(db/db) Mice with senescence marker protein-30 knockout (Lepr(db/db)Smp30(Y/-)) exhibit increases in small dense-LDL and severe fatty liver despite being fed a standard diet.

    Kondo Y, Hasegawa G, Okada H, Senmaru T, Fukui M, Nakamura N, Sawada M, Kitawaki J, Okanoue T, Kishimoto Y, Amano A, Maruyama N, Obayashi H, Ishigami A

    PloS one   8 ( 6 ) e65698  2013年  [査読有り]  [国際誌]

    DOI PubMed J-GLOBAL

  • Senescence marker protein-30/gluconolactonase expression in the mouse ovary during gestation.

    Kagami Y, Kondo Y, Handa S, Maruyama N, Ishigami A

    Biological & pharmaceutical bulletin   36 ( 12 ) 2005 - 2008  2013年  [査読有り]

    DOI PubMed

  • Smp30/Sod1ダブルノックアウトマウスにおける脂質代謝異常の解析

    近藤 嘉高, 半田 節子, 野田 義博, 丸山 直記, 清水 孝彦, 石神 昭人

    日本生化学会大会プログラム・講演要旨集   85回   3P - 878  2012年12月

  • Uric Acid Levels in Tissues and Plasma of Mice during Aging

    Mizuki Iwama, Yoshitaka Kondo, Kentaro Shimokado, Naoki Maruyama, Akihito Ishigami

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   35 ( 8 ) 1367 - 1370  2012年08月  [査読有り]

     概要を見る

    Here we quantified the uric acid (UA) levels in 11 tissues and plasma of C57BL/6 male mice to track its turnover during 3 to 30 months of aging. UA levels in the adrenal glands, heart, and spleen increased with aging until 30 months of age. Similarly, UA levels in the liver, kidneys, pancreas, and testes increased until the mice were 24 months old. UA levels also rose in the lungs and skeletal muscles from 3 to 6 months and 6 to 12 months, respectively, and then remained at almost the same levels until 30 months of age. In the skin, UA decreased from 3 to 6 months and then stayed nearly constant until 30 months of age. Moreover, the small intestines and plasma had quite stable UA levels during aging. Thus, our assessment of 11 tissue types from mice showed that the UA levels increased in most tissues during aging.

    DOI PubMed CiNii

  • Bioavailability of vitamin C from mashed potatoes and potato chips after oral administration in healthy Japanese men

    Yoshitaka Kondo, Chihana Higashi, Mizuki Iwama, Katsuyuki Ishihara, Setsuko Handa, Hiroyuki Mugita, Naoki Maruyama, Hidenori Koga, Akihito Ishigami

    BRITISH JOURNAL OF NUTRITION   107 ( 6 ) 885 - 892  2012年03月  [査読有り]

     概要を見る

    Potato (Solanum tuberosum) tubers contain vitamin C (VC) and commercial potato chips have more VC content per wet weight by dehydration during frying. However, intestinal absorption of VC from orally ingested potatoes and its transfer to the blood remains questionable. The present study was designed to determine whether the dietary consumption of potatoes affects VC concentration in plasma and urinary excretion of VC in human subjects. After overnight fasting, five healthy Japanese men between 22 and 27 years of age consumed 87 g mashed potatoes and 282 g potato chips. Each portion contained 50mg of VC, 50mg VC in mineral water and mineral water. Before and after a single episode of ingestion, blood and urine samples were collected every 30 min or 1 h for 8 h. When measured by subtraction of the initial baseline value before administration of potatoes from the values measured throughout the 8 h test period, plasma VC concentrations increased almost linearly up to 3 h. Subsequently, the values of potato-fed subjects were higher than those of water, but did not differ significantly from those of VC in water (P=0.14 and P=0.5). Less VC tended to be excreted in urine during the 8 h test than VC in water alone (17.0 (SEM 7.5) and 25.9 (SEM 8.8) v. 47.9 (SEM 17.9) mu mol/mmol creatinine). Upon human consumption, mashed potatoes and potato chips provide VC content that is effectively absorbed in the intestine and transferred to the blood. Clearly, potatoes are a readily available source of dietary VC.

    DOI PubMed

  • A Significant Relationship between Plasma Vitamin C Concentration and Physical Performance among Japanese Elderly Women

    Kyoko Saito, Tetsuji Yokoyama, Hideyo Yoshida, Hunkyung Kim, Hiroyuki Shimada, Yuko Yoshida, Hajime Iwasa, Yoko Shimizu, Yoshitaka Kondo, Setsuko Handa, Naoki Maruyama, Akihito Ishigami, Takao Suzuki

    JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES   67 ( 3 ) 295 - 301  2012年03月  [査読有り]

     概要を見る

    Maintenance of physical performance could improve the quality of life in old age. Recent studies suggested a beneficial relationship between antioxidant vitamin (eg, vitamin C) intake and physical performance in elderly people. The purpose of this study was to examine the relationship between plasma vitamin C concentration and physical performance among Japanese community-dwelling elderly women.
    This is a cross-sectional study involving elderly females residing in an urban area in Tokyo, Japan, in October 2006. We examined anthropometric measurements, physical performance, lifestyles, and plasma vitamin C concentration of participants.
    A total of 655 subjects who did not take supplements were analyzed. The mean age (+/- standard deviation) of participants was 75.7 +/- 4.1 years in this study. The geometric mean (geometric standard deviation) of plasma vitamin C concentration was 8.9 (1.5) mu g/mL. The plasma vitamin C concentration was positively correlated with handgrip strength, length of time standing on one leg with eyes open and walking speed, and inversely correlated with body mass index. After adjusting for the confounding factors, the quartile plasma vitamin C level was significantly correlated with the subject's handgrip strength (p for trend = .0004) and ability to stand on one leg with eyes open (p for trend = .049).
    In community-dwelling elderly women, the concentration of plasma vitamin C related well to their muscle strength and physical performance.

    DOI PubMed

  • Pancreatic insulin release in vitamin C-deficient senescence marker protein-30/gluconolactonase knockout mice

    Takafumi Senmaru, Masahiro Yamazaki, Hiroshi Okada, Mai Asano, Michiaki Fukui, Naoto Nakamura, Hiroshi Obayashi, Yoshitaka Kondo, Naoki Maruyama, Akihito Ishigami, Goji Hasegawa

    JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION   50 ( 2 ) 114 - 118  2012年03月  [査読有り]

     概要を見る

    We recently identified senescence marker protein-30 as the lactone-hydrolyzing enzyme gluconolactonase, which is involved in vitamin C biosynthesis. In this study, we investigated the effects of vitamin C on insulin secretion from pancreatic beta-cells using senescence marker protein-30/gluconolactonase knockout mice. In intraperitoneal glucose tolerance tests, vitamin C-deficient senescence marker protein-30/gluconolactonase knockout mice demonstrated impaired glucose tolerance with significantly lower blood insulin levels at 30 and 120 min post-challenge than in wild type mice (p&lt;0.01-0.05). In contrast, vitamin C-sufficient senescence marker protein-30/gluconolactonase knockout mice demonstrated significantly higher blood glucose and lower insulin only at the 30 min post-challenge time point (p&lt;0.05). Senescence marker protein-30/gluconolactonase knockout mice showed enhanced insulin sensitivity regardless of vitamin C status. Static incubation of islets revealed that 20 mM glucose-stimulated insulin secretion and islet ATP production were significantly decreased at 60 min only in vitamin C-deficient SMP30/GNL knockout mice relative to wild type mice (p&lt;0.05). These results indicate that the site of vitamin C action lies between glycolysis and mitochondrial oxidative phosphorylation, while SMP30 deficiency itself impairs the distal portion of insulin secretion pathway.

    DOI PubMed

  • Effect of vitamin C depletion on UVR-B induced cataract in SMP30/GNL knockout mice

    Yohei Ishikawa, Kouhei Hashizume, Seishi Kishimoto, Yu Tezuka, Hideo Nishigori, Naoki Yamamoto, Yoshitaka Kondo, Naoki Maruyama, Akihito Ishigami, Daijiro Kurosaka

    EXPERIMENTAL EYE RESEARCH   94 ( 1 ) 85 - 89  2012年01月  [査読有り]

     概要を見る

    We investigated whether decreased vitamin C (VC) in a mouse model increases lens opacity (cataract) induced by in vivo exposure to ultraviolet radiation type B (UVR-B).
    Senescence marker protein-30 (SMP30) knockout (1(0) mice, which cannot synthesize VC due to genetic disruption of the gluconolactonase (GNL) gene, were divided into 2 groups: VC sufficient (VC (+)) and VC deficient (VC (-)). Starting at 1 month of age, these groups had free access to water containing 0.0375 and 1.5 g/L of VC, respectively. SMP30 KO VC (-), SMP30 KO VC (+), and wild-type (WT) mice, all 14 weeks of age, were unilaterally exposed in vivo to UVR-B (200 mW/cm(2)) for 100 s twice a week for 3 weeks (total: 1200 mJ/cm(2)). At 48 h after the last UVR-B exposure, cataract morphology was documented, and the ratio of cataract induction was quantified as the cataract area ratio (opacity area/anterior capsule).
    UVR-B exposure induced cataract mainly at anterior sub-capsular in SMP30 KO VC (-), SMP30 KO VC (+), and WT mice. In SMP30 KO VC (-) lenses the opacities were more extensive than in SMP30 KO VC (+) or WT lenses (cataract area ratios: 59.3% +/- 10% vs. 32.2% +/- 11.7% or 29.0% +/- 9.0%; P &lt; 0.01).
    In conclusion, VC depletion may increase the susceptibility to develop UVR-B induced cataracts in mice unable to endogenously produce VC. (C) 2011 Elsevier Ltd. All rights reserved.

    DOI PubMed

  • Absorption and Excretion of Ascorbic Acid Alone and in Acerola (Malpighia emarginata) Juice: Comparison in Healthy Japanese Subjects

    Eriko Uchida, Yoshitaka Kondo, Akiko Amano, Shingo Aizawa, Takayuki Hanamura, Hitoshi Aoki, Kenichi Nagamine, Takeshi Koizumi, Naoki Maruyama, Akihito Ishigami

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   34 ( 11 ) 1744 - 1747  2011年11月  [査読有り]

     概要を見る

    It has been suggested that some food components, such as bioflavonoids, affect the bioavailability of ascorbic acid in humans. Since little is known in Japan about the effective intake of this dietary requirement, we tested young Japanese males after the ingestion of commercial ascorbic acid or acerola (Malpighia emarginata DC.) juice to compare the quantities absorbed and excreted. Healthy Japanese subjects received a single oral dose of ascorbic acid solution (50, 100, 200 or 500 mg) and received distilled water as a reference at intervals of 14 d or longer. All subjects were collected blood and urine until 6 h after ingestion and evaluated for time-dependent changes in plasma and urinary ascorbic acid levels. Predictably, the area under the curve (AUC) values in plasma and urine after ingestion increased dose-dependently. Next, each subject received diluted acerola juice containing 50 mg ascorbic acid. Likewise, their plasma and urinary ascorbic acid concentrations were measured. In plasma, the AUC value of ascorbic acid after ingestion of acerola juice tended to be higher than that from ascorbic acid alone. In contrast, the urinary excretion of ascorbic acid at 1, 2 and 5 h after ingestion of acerola juice were significantly less than that of ascorbic acid. These results indicate that some component of acerola juice favorably affected the absorption and excretion of ascorbic acid.

    DOI CiNii

  • Smp30/Sod1ダブルノックアウトマウスにおける肝臓の組織学的解析

    岩間 水輝, 野田 義博, 清水 孝彦, 近藤 嘉高, 丸山 直記, 石神 昭人

    ビタミン   85 ( 4 ) 242 - 242  2011年04月

  • Smp30-1-Sod1-1-ダブルノックアウトマウスにおける血液脂質成分および肝臓の組織学的解析

    岩間 水輝, 野田 義博, 清水 孝彦, 近藤 嘉高, 丸山 直記

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   83回・33回   4P - 0359  2010年12月

  • VC摂取によるCOPD発症リスク軽減効果の検討

    小池 建吾, 瀬山 邦明, 石神 昭人, 近藤 嘉高, 飛野 和則, 児玉 裕三, 関谷 充晃, 丸山 直記, 高橋 和久

    順天堂医学   56 ( 5 ) 492 - 492  2010年10月

  • ビタミンC枯渇条件下ではマウス肺に肺気腫が生じる

    小池 建吾, 瀬山 邦明, 近藤 嘉高, 丸山 直記, 石神 昭人, 高橋 和久

    順天堂医学   56 ( 5 ) 510 - 511  2010年10月

  • Pathophysiological significance of senescence marker protein-30

    Naoki Maruyama, Akihito Ishigami, Yoshitaka Kondo

    GERIATRICS & GERONTOLOGY INTERNATIONAL   10 ( Supplement 1 ) S88 - S98  2010年07月  [査読有り]

     概要を見る

    A novel rat liver protein of 30 kDa, SMP30 decreases with aging. This protein is expressed most prominently in the liver and kidneys among the various organs. Its gene is located on the X chromosome. No functional domain was recognized in the entire amino acid sequence. Recently, we found a homology between rat SMP30 and two species of bacterial gluconolactonase (EC 3.1.1.17). The lactonase reaction with l-gulono-gamma-lactone is the penultimate step in vitamin C (l-ascorbic acid) biosynthesis. SMP30-knockout (KO) mice fed a vitamin C-deficient diet displayed symptoms of scurvy. In SMP30-KO mice, hepatocytes were more susceptible to apoptosis induced by TNF-alpha plus actinomycin D than hepatocytes from wild-type mice. Two morphological features considered to be a hallmark of senescence are apparent in SMP30-KO mice. At 12 months of age, SMP30-knockout mice had clearly visible deposits of lipofuscin and senescence-associated beta-galactosidase (SA-beta-GAL) in their renal tubular epithelia. These features are compatible with high electron dense deposits in lysosomes. This observation suggests that the SMP30-knockout mouse is a useful model of ordinal senescence. Geriatr Gerontol Int 2010; 10 (Suppl. 1): S88-S98.

    DOI CiNii

  • Complete lack of vitamin C intake generates pulmonary emphysema in senescence marker protein-30 knockout mice

    Kengo Koike, Yoshitaka Kondo, Mitsuaki Sekiya, Yasunori Sato, Kazunori Tobino, Shin-iciro Iwakami, Sataro Goto, Kazuhisa Takahashi, Naoki Maruyama, Kuniaki Seyama, Akihito Ishigami

    AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY   298 ( 6 ) L784 - L792  2010年06月  [査読有り]

     概要を見る

    Koike K, Kondo Y, Sekiya M, Sato Y, Tobino K, Iwakami S, Goto S, Takahashi K, Maruyama N, Seyama K, Ishigami A. Complete lack of vitamin C intake generates pulmonary emphysema in senescence marker protein-30 knockout mice. Am J Physiol Lung Cell Mol Physiol 298: L784-L792, 2010. First published February 19, 2010; doi:10.1152/ajplung.00256.2009.-Vitamin C (VC) is a potent antioxidant and plays an essential role in collagen synthesis. As we previously reported, senescence marker protein-30 (SMP30) knockout (KO) mice cannot synthesize VC due to the genetic disruption of gluconolactonase (i.e., SMP30). Here, we utilized SMP30 KO mice deprived of VC and found that VC depletion caused pulmonary emphysema due to oxidative stress and a decrease of collagen synthesis by the third month of age. We grew SMP30 KO mice and wild-type (WT) mice on VC-free chow and either VC water [VC(+)] or plain water [VC(-)] after weaning at 4 wk of age. Morphometric findings and reactive oxygen species (ROS) in the lungs were evaluated at 3 month of age. No VC was detected in the lungs of SMP30 KO VC(-) mice, but their ROS increased 50.9% over that of the VC(+) group. Moreover, their collagen content in the lungs markedly decreased, and their collagen I mRNA decreased 82.2% compared with that of the WT VC(-) group. In the SMP30 KO VC(-) mice, emphysema developed [21.6% increase of mean linear intercepts (MLI) and 42.7% increase of destructive index compared with VC(+) groups], and the levels of sirtuin 1 (Sirt1) decreased 16.8%. However, VC intake increased the MLI 16.2% and thiobarbituric acid reactive substances 22.2% in WT mice, suggesting that an excess of VC can generate oxidative stress and may be harmful during this period of lung development. These results suggest that VC plays an important role in lung development through affecting oxidant-antioxidant balance and collagen synthesis.

    DOI PubMed

  • Hypoglycemia due to Ectopic Secretion of Insulin-like Growth Factor-I in a Patient with an Isolated Sarcoidosis of the Spleen

    Yuiko Ogiwara, Seijiro Mori, Mizuki Iwama, Motoji Sawabe, Minoru Takemoto, Nobuo Kanazawa, Koh Furuta, Izumi Fukuda, Yoshitaka Kondo, Yoshiyuki Kimbara, Yoshiaki Tamurai, Yuko Chiba, Atsushi Araki, Koutaro Yokote, Naoki Maruyama, Hideki Ito

    ENDOCRINE JOURNAL   57 ( 4 ) 325 - 330  2010年04月  [査読有り]

     概要を見る

    Hypoglycemia is reported to be one of the manifestations of a patient with hypothalamic sarcoid infiltrates due to impaired counter-regulation of glucose. But, without hypothalamic lesion, patients with sarcoidosis would not be expected to have hypoglycemia. We recently identified a patient with an isolated sarcoidosis of the spleen who had experienced frequent fasting hypoglycemia which completely disappeared after splenectomy. During hypoglycemia, serum insulin was undetectable. Endocrinological examination revealed no abnormality. The objective was to investigate whether the patient&apos;s hypoglycemia was due to ectopic secretion of an insulin-mimetic factor by the splenic sarcoidosis. Serum insulin-like growth factor-I (IGF-I) and IGF-II were measured by RIA. Serum visfatin and free IGF-I were by ELISA. A high molecular weight form of IGF-I I, termed "big: IGF-II, was identified by Western blotting. Tissue IGF-I was quantified by real time RT-PCR after RNA extraction. Before operation, total and free serum IGF-I, serum IGF-II and serum visfatin were within reference range. Big IGF-II was not detected in patient&apos;s serum extract. After operation, hypoglycemia did not recur and serum insulin returned to normal, while serum IGF-I decreased by half the preoperative level. RT-PCR revealed that mRNA level of IGF-I in the sarcoidosis tissue was about 1.8-fold greater than that in the normal spleen tissue. These data suggest that ectopic secretion of IGF-I by the splenic sarcoidosis and its direct access to the liver via the portal vein might cause fasting hypoglycemia mainly by suppressing hepatic gluconeogenesis.

    DOI CiNii

  • SMP30ノックアウトマウスにおけるビタミンCの肺気腫治療効果の検討

    小池 建吾, 瀬山 邦明, 石神 昭人, 近藤 嘉高, 児玉 裕三, 関谷 充晃, 丸山 直記, 高橋 和久

    日本呼吸器学会雑誌   48 ( 増刊 ) 150 - 150  2010年03月

  • Senescence Marker Protein-30/Gluconolactonase Deletion Worsens Glucose Tolerance through Impairment of Acute Insulin Secretion

    Goji Hasegawa, Masahiro Yamasaki, Mayuko Kadono, Muhei Tanaka, Mai Asano, Takafumi Senmaru, Yoshitaka Kondo, Michiaki Fukui, Hiroshi Obayashi, Naoki Maruyama, Naoto Nakamura, Akihito Ishigami

    ENDOCRINOLOGY   151 ( 2 ) 529 - 536  2010年02月  [査読有り]

     概要を見る

    Senescence marker protein-30 (SMP30) is an androgen-independent factor that decreases with age. We recently identified SMP30 as the lactone-hydrolyzing enzyme gluconolactonase (GNL), which is involved in vitamin C biosynthesis in animal species. To examine whether the age-related decrease in SMP30/GNL has effects on glucose homeostasis, we used SMP30/GNL knockout ( KO) mice treated with L-ascorbic acid. In an ip glucose tolerance test at 15 wk of age, blood glucose levels in SMP30/GNL KO mice were significantly increased by 25% at 30 min after glucose administration compared with wildtype (WT) mice. Insulin levels in SMP30/GNL KO mice were significantly decreased by 37% at 30 min after glucose compared with WT mice. Interestingly, an insulin tolerance test showed a greater glucose-lowering effect in SMP30/GNL KO mice. High-fat diet feeding severely worsened glucose tolerance in both WT and SMP30/GNL KO mice. Morphometric analysis revealed no differences in the degree of high-fat diet-induced compensatory increase in beta-cell mass and proliferation. In the static incubation study of islets, insulin secretion in response to 20 mM glucose or KCl was significantly decreased in SMP30/GNL KO mice. On the other hand, islet ATP content at 20 mM in SMP30/GNL KO mice was similar to that in WT mice. Collectively, these data indicate that impairment of the early phase of insulin secretion due to dysfunction of the distal portion of the secretion pathway underlies glucose intolerance in SMP30/GNL KO mice. Decreased SMP30/GNL may contribute to the worsening of glucose tolerance that occurs in normal aging. (Endocrinology 151: 529-536, 2010)

    DOI PubMed

  • ビタミンC摂取によるCOPD発症リスク軽減効果の検討

    小池 建吾, 瀬山 邦明, 石神 昭人, 近藤 嘉高, 飛野 和則, 児玉 裕三, 関谷 充晃, 丸山 直記, 高橋 和久

    順天堂医学   55 ( 4 ) 525 - 525  2009年12月

  • Effect of vitamin C depletion on age-related hearing loss in SMP30/GNL knockout mice.

    Kashio A, Amano A, Kondo Y, Sakamoto T, Iwamura H, Suzuki M, Ishigami A, Yamasoba T

    Biochemical and biophysical research communications   390   394 - 398  2009年12月  [査読有り]

    DOI PubMed

  • 抗酸化剤摂取はSenescence-accelerated mice(SAM)P1の老化を抑制するか?

    小池 建吾, 瀬山 邦明, 袁 益明, 秋吉 妙子, 岩間 水輝, 天野 晶子, 佐藤 安訓, 近藤 嘉高, 石神 昭人, 後藤 佐多良, 丸山 直記, 高橋 和久

    順天堂医学   55 ( 3 ) 370 - 370  2009年09月

  • SMP30ノックアウトマウスにおけるビタミンCの肺気腫発生予防効果の検討

    小池 建吾, 瀬山 邦明, 近藤 嘉高, 児玉 裕三, 関谷 充晃, 丸山 直記, 石神 昭人, 高橋 和久

    順天堂医学   55 ( 3 ) 377 - 377  2009年09月

  • Effects of vitamin C deficiency on the skin of the senescence marker protein-30 (SMP30) knockout mouse

    Koji Y. Arai, Yasunori Sato, Yoshitaka Kondo, Chikako Kudo, Hiroyuki Tsuchiya, Yoshihiro Nomura, Akihito Ishigami, Toshio Nishiyama

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   385 ( 3 ) 478 - 483  2009年07月  [査読有り]

     概要を見る

    Senescence marker protein-30 (SMP30) is a gluconolactonase required for vitamin C (VC) synthesis. We examined effects of VC deficiency on the mouse skin using SMP30 knockout (KO) mice. SMP30 KO or wild type male mice were weaned around day 30 of age, and fed VC-deficient diet. They were given either VC water or control water. VC deficiency for 36 days did not affect skin hydroxyproline contents, while VC deficiency for 60 days decreased the hydroxyproline levels. Levels of some collagen mRNAs were different among the groups, but did not correlate with skin VC levels. The epidermis was morphologically abnormal in VC-deficient SMP30 KO mouse at 60 days after the weaning. Interestingly, the hair cycle was not synchronized among the groups. These data suggest low susceptibility of the mouse skin to VC deficiency and involvement of VC in the regulation of keratinocyte function and hair cycle in vivo. (C) 2009 Elsevier Inc. All rights reserved.

    DOI PubMed

  • SMP30ノックアウトマウスにおけるビタミンCの肺気腫発生予防効果の検討

    小池 建吾, 瀬山 邦明, 石神 昭人, 近藤 嘉高, 吉見 格, 児玉 裕三, 関谷 充晃, 丸山 直記, 高橋 和久

    日本呼吸器学会雑誌   47 ( 増刊 ) 210 - 210  2009年05月

  • Vitamin C depletion increases superoxide generation in brains of SMP30/GNL knockout mice

    Yoshitaka Kondo, Toru Sasaki, Yasunori Sato, Akiko Amano, Shingo Aizawa, Mizuki Iwama, Setsuko Handa, Nobuko Shimada, Mitsugu Fukuda, Masumi Akita, Jaewon Lee, kyu-Shik Jeong, Naoki Maruyama, Akihito Ishigami

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   377 ( 1 ) 291 - 296  2008年12月  [査読有り]

     概要を見る

    Vitamin C (VC) has a strong antioxidant function evident as its ability to scavenge superoxide radicals in vitro. We verified that this property actually exists in vivo by using a real-time imaging system in which Lucigenin is the chemiluminescent probe for detecting superoxide in senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knowkcout (KO) mice, which cannot synthesize VC in vivo. SMP30/GNL KO mice were given 1.5 g/L VC [VC(+)] for 2, 4, or 8 weeks or denied VC [VC(-)]. At 4 and 8 weeks, VC levels in brains from VC(-) KO mice were &lt;6% of that in VC(+) KO mice. Accordingly, superoxide-dependent chemiluminescence levels determined by ischemia-reperfusion at the 4- and 8 weeks test intervals were 3.0-fold and 2.1-fold higher, respectively, in VC(-) KO mice than in VC(+) KO mice, However, total superoxide dismutase activity and protein levels were not altered. Thus, VC depletion specifically increased superoxide generation in a model of the living brain. (C) 2008 Elsevier Inc. All rights reserved.

    DOI PubMed

  • Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice

    Yasunori Sato, Shizuo Kajiyama, Akiko Amano, Yoshitaka Kondo, Toru Sasaki, Setsuko Handa, Ryoya Takahashi, Michiaki Fukui, Goji Hasegawa, Naoto Nakamura, Hikohito Fujinawa, Toyotaka Mori, Mitsuhiro Ohta, Hiroshi Obayashi, Naoki Maruyama, Akihito Ishigami

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   375 ( 3 ) 346 - 350  2008年10月  [査読有り]

     概要を見る

    Hydrogen is an established anti-oxidant that prevents acute oxidative Stress. To Clarify the mechanism of hydrogen&apos;s effect in the brain, we administered hydrogen-rich pure water (H(2)) to senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice. which cannot synthesize vitamin C (VC) also a well-known anti-oxidant. These KO mice were divided into three groups: recipients of H(2), VC, or pure water (H(2)O), administered for 33 days. VC levels in H(2) and H(2)O groups were &lt;6% of those in the VC group. Subsequently, superoxide formation during hypoxia-reoxygenation treatment of brain slices from these groups was estimated by a real-time biography imaging system, which models living brain tissues, with Lucigenin used as chemiluminescence probe for superoxide. A significant 27.2% less superoxide formed in the H(2) group subjected to ischemia-reperfusion than in the H(2)O group. Thus hydrogen-rich pure water acts as an anti-oxidant in the brain slices and prevents superoxide formation. (C) 2008 Elsevier Inc. All rights reserved.

    DOI PubMed

  • Vitamin C is not essential for carnitine biosynthesis in vivo: Verification in vitamin C-depleted senescence marker protein-30/gluconolactonase knockout mice

    Hajime Furusawa, Yasunori Sato, Yasukazu Tanaka, Yoko Inai, Akiko Amano, Mizuki Iwama, Yoshitaka Kondo, Setsuko Handa, Akira Murata, Morimitsu Nishikimi, Sataro Goto, Naoki Maruyama, Ryoya Takahashi, Akihito Ishigami

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   31 ( 9 ) 1673 - 1679  2008年09月  [査読有り]

     概要を見る

    Carnitine is an essential cofactor in the transport of long-chain fatty acids into the mitochondrial matrix and plays an important role in energy production via beta-oxidation. Vitamin C (VC) has long been considered a requirement for the activities of two enzymes in the carnitine biosynthetic pathway, i.e., 6-N-trimethyllysine dioxygenase and gamma-butyrobetaine dioxygenase. Our present study using senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which cannot synthesize VC in vivo, led to the conclusion that this notion is not true. After weaning at 40 d of age, SMP30/GNL KO mice were fed a diet lacking VC and carnitine, (hen given water containing 1.5 g/I VC (VC(+) mice) or no VC (VC(-) mice) for 75 d. Subsequently, total VC and carnitine levels were measured in the cerebrum, cerebellum, liver, kidney, soleus muscle, extensor digitorum longus muscle, heart, plasma and serum. The total VC levels in all tissues an d plasma from VC(-) SMP30/GNL KO mice were negligible, i.e., &lt;2% of the levels in SMP30/GNL KO VC(+) mice; however, the total carnitine levels of both groups were similar in all tissues and serum. In addition, carnitine was produced by incubated liver homogenates from the VC-depleted SMP30/GNL KO mice irrespective of the presence or absence of 1mM VC. Collectively, these results indicate that VC is not essential for carnitine biosynthesis in vivo.

    DOI

  • ビタミンC摂取によるCOPD発症リスク軽減効果の検討

    小池 建吾, 瀬山 邦明, 石神 昭人, 近藤 嘉高, 佐藤 安訓, 袁 益明, 秋吉 妙子, 児玉 裕三, 関谷 充晃, 岩間 水輝, 天野 晶子, 後藤 佐多良, 丸山 直記, 高橋 和久

    順天堂医学   54 ( 3 ) 388 - 388  2008年09月

  • SMP30ノックアウトマウスにおけるビタミンCが肺の老化に及ぼす影響

    小池 建吾, 瀬山 邦明, 石神 昭人, 近藤 嘉高, 佐藤 安訓, 袁 益明, 秋吉 妙子, 児玉 裕三, 関谷 充晃, 岸本 祐樹, 岩間 水輝, 天野 晶子, 丸山 直記, 高橋 和久

    順天堂医学   54 ( 3 ) 400 - 400  2008年09月

  • SMP30ノックアウトマウスにおけるビタミンC摂取によるCOPD発症リスク軽減効果の検討

    小池 建吾, 瀬山 邦明, 石神 昭人, 近藤 嘉高, 佐藤 安訓, 袁 益明, 秋吉 妙子, 児玉 裕三, 関谷 充晃, 岸本 祐樹, 岩間 水輝, 天野 晶子, 丸山 直記, 高橋 和久

    順天堂医学   54 ( 2 ) 236 - 236  2008年06月

  • A selective NFkB inhibitor, DHMEQ, reduced atherosclerosis in ApoE-deficient mice

    Tsuyoshi Chiba, Yoshitaka Kondo, Shohei Shinozaki, Eiji Kaneko, Akihito Ishigami, Naoki Maruyama, Kazuo Umezawa, Kentaro Shimokado

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   13 ( 6 ) 308 - 313  2006年12月  [査読有り]

     概要を見る

    Background and Purpose: Atherosclerosis is a chronic inflammatory process, and anti-inflammatory agents potentially inhibit the development of atherosclerosis. We tested whether a novel NFkB inhibitor reduces atherosclerosis.
    Methods: Dehydroxymethylepoxyquinomicin (10 mg/kg) or vehicle (chloromethyl cellulose) was injected intraperitoneally into apoE-deficient mice three times a week for 16 weeks. The entire aorta was excised and atherosclerotic area was determined at 4 and 16 weeks. Serum levels of cholesterol, triglyceride, TNF-alpha and adiponectin were also measured.
    Results: The atherosclerotic area was significantly smaller in mice treated with dehydroxymethyl-epoxyquinomicin both at 4 and 16 weeks. There was no significant difference in body weight or serum levels of cholesterol, triglyceride, and adiponectin.
    Conclusions: A new NFkB inhibitor, dehydroxymethylepoxyquinomicin, reduced atherosclerosis without affecting plasma lipid levels in apoE-deficient mice.

    DOI CiNii

  • Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy

    Y Kondo, Y Inai, Y Sato, S Handa, S Kubo, K Shimokado, S Goto, M Nishikimi, N Maruyama, A Ishigami

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   103 ( 15 ) 5723 - 5728  2006年04月  [査読有り]

     概要を見る

    We originally identified senescence marker protein 30 (SMP30) as a distinctive protein whose expression decreases in an androgen-independent manner with aging. Here, we report its sequence homology found in two kinds of bacterial gluconolactonases (GNLs) by using the BLAST search. Then, through a biochemical study, we identify SMP30 as the lactone-hydrolyzing enzyme GNL of animal species. SMP30 purified from the rat liver had lactonase activity toward various aldonolactones, such as D- and L-glucono-delta-lactone, D- and L-gulono-gamma-lactone, and D- and L-galactono-gamma-lactone, with a requirement for Zn2+ or Mn2+ as a cofactor. Furthermore, in SMP30 knockout mice, no GNL activity was detectable in the liver. Thus, we conclude that SMP30 is a unique GNL in the liver. The lactonase reaction with L-gulono-gamma-lactone is the penultimate step in L-ascorbic acid (AA) biosynthesis, and the essential role of SMP30 in this synthetic process was verified here by a nutritional study using SMP30 knockout mice. These knockout mice (n = 6), fed a vitamin C-deficient diet, did not thrive; i.e., they displayed symptoms of scurvy such as bone fracture and rachitic rosary and then died by 135 days after the start of receiving the deficient diet. The AA levels in their livers and kidneys at the time of death were &lt; 1.6% of those in WT control mice. In addition, by using the SMP30 knockout mouse, we demonstrate that the alternative pathway of AA synthesis involving D-glucurono-gamma-lactone operates in vivo, although its flux is fairly small.

    DOI PubMed

  • Senescence marker protein-30 (SMP30) induces formation of microvilli and bile canaliculi in Hep G2 cells

    A Ishigami, T Fujita, H Inoue, S Handa, S Kubo, Y Kondo, N Maruyama

    CELL AND TISSUE RESEARCH   320 ( 2 ) 243 - 249  2005年05月  [査読有り]

     概要を見る

    Senescence marker protein-30 (SMP30) is an androgen-independent factor that decreases with aging. To elucidate the physiological functions of SMP30, we transfected human SMP30 cDNA into the human hepatoma cell line, Hep G2. These Hep G2/SMP30 transfectants, which stably expressed large amounts of SMP30, proliferated at a slower rate and synthesized less DNA than mock transfectants (Hep G2/pcDNA3 controls). Thus, enhanced expression of SMP30 retarded the growth of Hep G2/SMP30 cells. Ultrastructural studies by scanning electron microscopy revealed numerous microvilli covering the surfaces of Hep G2/SMP30 cells, whereas few microvilli appeared on control cells. Subsequently, transmission electron microscopy revealed that groups of Hep G2/SMP30 cells exhibited bile canaliculi and possessed specialized adhesion contacts, such as tight junctions and desmosomes, at interplasmic membranes. However, in controls, units of only two cells were seen, and these lacked specialized adhesion junctions. Moesin and ZO-1 are known to be concentrated in microvilli and at tight junctions, respectively. Double-immunostaining was performed to examine whether moesin and ZO-1 were expressed in bile canaliculi with microvilli at the apical regions of Hep G2/SMP30 cells. The intensity of moesin and ZO-1 staining in the contact regions of each cell was markedly higher in Hep G2/SMP30 than in control cells. Moreover, moesin stained more interior areas, which corresponded to the microvilli of bile canaliculi. Clearly, bile canaliculi with microvilli formed at the apical ends of Hep G2/SMP30 cells. These results indicate that SMP30 has an important physiological function as a participant in cell-to-cell interactions and imply that the down-regulation of SMP30 during the aging process contributes to the deterioration of cellular interactivity.

    DOI PubMed

  • Senescence marker protein-30 is a unique enzyme that hydrolyzes diisopropyl phosphorofluoridate in the liver

    Y Kondo, A Ishigami, S Kubo, S Handa, K Gomi, K Hirokawa, N Kajiyama, T Chiba, K Shimokado, N Maruyama

    FEBS LETTERS   570 ( 1-3 ) 57 - 62  2004年07月  [査読有り]

     概要を見る

    Senescence marker protein-30 (SMP30) was originally identified as a novel protein in the rat liver, the expression of which decreases androgen-independently with aging. We have now characterized a unique property of SMP30, the hydrolysis of diisopropyl phosphorofluoridate (DFP), which is similar to the chemical warfare nerve agents sarine, soman and tabun. Hydrolysis of DFP was stimulated equally well by 1 MM MgCl2, MnCl2 or CoCl2, to a lesser extent by 1 mM CdCl2 but not at all by 1 mM CaCl2. No Ca-45(2+) -binding activity was detected for purified SMP30, suggesting that SMP30 is not a calcium-binding protein, as others previously stated. Despite the sequence similarity between SMP30 and a serum paraoxonase (PON), the inability of SMP30 to hydrolvze PON-specific substrates such as paraoxon, dihydrocoumarin gamma-nonalactone, and delta-dodecanolactone indicate that SMP30 is distinct from the PON family. We previously established SMP30 knockout mice and have now tested DFPase activity in their livers. The livers from wild-type mice contained readily detectable DFPase activity, whereas no such enzyme activity was found in livers from SMP30 knockout mice. Moreover, the hepatocytes of SMP30 knockout mice were far more susceptible to DFP-induced cytotoxicity than those from the wild-type. These results indicate that SMP30 is a unique DFP hydrolyzing enzyme in the liver and has an important detoxification effect on DFP. Consequently, a reduction of SMP30 expression might account for the age-associated deterioration of cellular functions and enhanced susceptibility to harmful stimuli in aged tissue. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    DOI PubMed CiNii

  • SMP30 deficiency in mice causes an accumulation of neutral lipids and phospholipids in the liver and shortens the life span

    A Ishigami, Y Kondo, R Nanba, T Ohsawa, S Handa, S Kubo, M Akita, N Maruyama

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   315 ( 3 ) 575 - 580  2004年03月  [査読有り]

     概要を見る

    Senescence marker protein-30 (SMP30) is an androgen-independent factor that decreases with aging. SMP30-deficient (SMP30Y/-) mice are viable and fertile but lower in body weight and shorter in life span than the wild-type. In the electron microscope, hepatocytes from SMP30Y/- but not the wild-type mice at 12 months of age clearly contained many lipid droplets, abnormally enlarged mitochondria with indistinct cristae, and enlarged lysosomes filled with electron-dense bodies. In liver specimens from SMP30Y/- mice, the marked number of lipid droplets visible around the central vein increased notably in size and amount as the animals aged. Biochemical analysis of neutral lipids, total hepatic triglyceride, and cholesterol from SMP30Y/- mice showed approximately 3.6- and 3.3-fold higher levels, respectively. than those from age-matched wild-type mice. Moreover, values for total hepatic phospholipids from SMP30Y/- mice were approximately 3.7-fold higher than those for their wild-type counterparts. By thin-layer chromatography analysis, phosphatidylethanolamine, cardiolipin, phosphatidylcholine, phosphatidylserine, and sphingomyelin accumulations were detected separately in lipid extracts from SMP30Y/- mouse livers and provided results that strongly indicate the profound effect of an SMP30 deficiency on the metabolism of these neutral lipids and phospholipids. Conceivably, this abnormality of lipid metabolism is sufficient to curtail the life span of SMP30-deficient mice. (C) 2004 Elsevier Inc. All rights reserved.

    DOI PubMed CiNii

  • Senescence marker protein-30 as a novel antiaging molecule

    DY Feng, Y Kondo, A Ishigami, M Kuramoto, T Machida, N Maruyama

    STRATEGIES FOR ENGINEERED NEGLIGIBLE SENESCENCE: WHY GENUINE CONTROL OF AGING MAY BE FORESEEABLE   1019   360 - 364  2004年  [査読有り]

     概要を見る

    Senescence marker protein-30 (SMP30), composed of 299 amino acids, has an approximate molecular mass of 32-34 kDa and has a pI 4.9 in charge. The amino acid alignment from various animal species revealed a highly conserved structure. SMP30 has an enzyme activity hydrolyzing sarin, soman, and tabun, known as lethal toxic nerve chemicals. We analyzed the organophosphatase activity of SMP30 using DFP as a substrate. This DFPase activity is revealed in a dose-dependent manner in the presence of magnesium ions. We investigated the intracellular localization of SMP30. It is localized in both the cytoplasm and nucleus. To confirm the presence of SMP30 in the nucleus, we prepared nuclear and cytoplasmic extracts from isolated cultured hepatocytes. Western blotting showed that SMP30 was detected in both extracts. Because the expression is reduced by carbon tetrachloride, one can speculate that the expression is modulated by oxidative stress increased with aging.

    DOI PubMed

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Misc

  • マウス臓器におけるグルコン酸キナーゼの遺伝子発現に関する研究

    袁一ぶん, 王梓, 吉井幸, 石神昭人, 千葉卓哉, 近藤嘉高

    日本分子生物学会年会プログラム・要旨集(Web)   43rd  2020年

    J-GLOBAL

  • α-Klothoマウスの肺におけるヘパラン硫酸プロテオグリカンの分泌抑制

    赤阪啓子, 灘中里美, 近藤嘉高, 石神昭人, 北川裕之, 萬谷博, 遠藤玉夫

    日本薬学会年会要旨集(CD-ROM)   139th  2019年

    J-GLOBAL

  • ビタミンCによるバンコマイシン誘発薬剤性腎障害の予防効果

    瀧川正紀, 瀧川正紀, 近藤嘉高, 島崎良知, 島崎良知, 石井敏浩, 森淑子, 森淑子, 石神昭人

    日本薬学会年会要旨集(CD-ROM)   138th  2018年

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  • 授乳期のビタミンC欠乏は,子の肝臓における脂質代謝関連遺伝子のDNA脱メチル化を阻害する。

    川堀健一, 橋本貢士, 袁勲梅, 辻本和峰, 榛澤望, 近藤嘉高, 石神昭人, 川崎佑季, 幸田尚, 小川佳宏, 小川佳宏

    日本内分泌学会雑誌   94 ( 1 )  2018年

    J-GLOBAL

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    赤阪(萬谷)啓子, 灘中里美, 近藤嘉高, 石神昭人, 北川裕之, 萬谷博, 遠藤玉夫

    日本生化学会大会(Web)   91st  2018年

    J-GLOBAL

  • 授乳期のビタミンC欠乏は,子の肝臓における脂質代謝関連遺伝子のDNAメチル化を亢進する

    川堀健一, 橋本貢士, 袁勲梅, 辻本和峰, 榛澤望, 近藤嘉高, 石神昭人, 川崎佑季, 幸田尚, 小川佳宏, 小川佳宏, 小川佳宏

    糖尿病(Web)   61 ( Suppl )  2018年

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  • 雌雄マウスでのアスコルビン酸欠乏が骨格筋に及ぼす影響

    滝沢 晶子, 近藤 嘉高, 滝野 有花, 船越 智子, 野田 義博, 町田 修一, 相垣 敏郎, 石神 昭人

    生命科学系学会合同年次大会   2017年度   [2P - 1004]  2017年12月

  • ビタミンC欠乏が骨格筋に及ぼす影響

    石神昭人, 滝沢晶子, 近藤嘉高

    ビタミン   91 ( 9 )  2017年

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    近藤嘉高, 青木仁史, 笹原由雅, 滝野有花, 杉原伸郎, 石神昭人

    日本生化学会大会(Web)   90th  2017年

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  • COPDモデルマウスを用いたビタミンC治療による肺胞修復メカニズムの遺伝子学的解析

    荒野直子, 佐藤匡, 烏谷惠子, BASKORO Hario, 鈴木洋平, 三井亜樹, 児玉裕三, 近藤嘉高, 石神昭人, 瀬山邦明, 高橋和久

    日本呼吸器学会誌(Web)   6  2017年

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  • タンパク質摂取量の違いが中高齢マウスの筋再生に及ぼす影響

    近藤嘉高, 青木仁史, 笹原由雅, 成田昂平, 滝沢晶子, 石神昭人

    日本栄養・食糧学会大会講演要旨集   71st  2017年

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    滝沢晶子, 滝沢晶子, 近藤嘉高, 町田修一, 相垣敏郎, 石神昭人

    ビタミン   91 ( 4 )  2017年

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    河島早紀, 河島早紀, 滝野有花, 近藤嘉高, 永田喜三郎, 斉藤紀克, 大澤肇, 栗田克己, 佐藤安訓, 吉田雅幸, 石神昭人

    日本生化学会大会(Web)   90th  2017年

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  • アロマターゼノックアウトマウスにおけるエストロゲン欠乏が肝臓での脂質代謝に及ぼす影響

    天野 晶子, 近藤 嘉高, 野田 義博, 町田 修一, 尾林 博, 石神 昭人

    日本生化学会大会プログラム・講演要旨集   89回   [1P - 296]  2016年09月

  • エストロゲン合成酵素アロマターゼ(Cyp19)の遺伝子欠損による脂質代謝への影響

    天野 晶子, 近藤 嘉高, 野田 義博, 町田 修一, 尾林 博, 石神 昭人

    基礎老化研究   40 ( Suppl. ) 35 - 35  2016年05月

  • SOD1欠損とアスコルビン酸不足が脂質代謝に及ぼす影響

    近藤嘉高, 石神昭人

    日本生化学会大会(Web)   89th  2016年

    J-GLOBAL

  • マウス骨格筋でのぺプチジルアルギニンデイミナーゼ2(PAD2)の局在性

    成田昂平, 成田昂平, 近藤嘉高, 増冨裕文, 増冨裕文, 吉田雅之, 石神昭人

    日本生化学会大会(Web)   89th  2016年

    J-GLOBAL

  • マウス骨格筋におけるペプチジルアルギニンデイミナーゼ2(PAD2)の生化学的解析

    成田昂平, 成田昂平, 近藤嘉高, 増冨裕文, 吉田雅幸, 石神昭人

    日本分子生物学会年会プログラム・要旨集(Web)   39th  2016年

    J-GLOBAL

  • 新規に開発した抗化学修飾シトルリン化モノクローナル抗体を用いた脳におけるシトルリン化タンパク質の検出

    近藤嘉高, 成田昂平, 石神昭人

    日本分子生物学会年会プログラム・要旨集(Web)   39th  2016年

    J-GLOBAL

  • Vitamin C deficiency exacerbates pulmonary dysfunction and emphysema in a mouse model of chronic obstructive pulmonary diseases

    Tsuyoshi Shuto, Yuki Sakaguchi, Hirofumi Nohara, Shunsuke Kamei, Haruka Fujikawa, Yoshitaka Kondo, Akihito Ishigami, Hirofumi Kai

    JOURNAL OF PHARMACOLOGICAL SCIENCES   128 ( 3 ) S127 - S127  2015年07月

    研究発表ペーパー・要旨(国際会議)  

  • Ascorbic acid欠乏は,Cav3.2T型Ca2+チャネルを介する痛みを増強する

    坪田真帆, 上坊健太, 三木好輝, 福田亮太郎, 関口富美子, 近藤嘉高, 高橋経太, 増富裕文, 石神昭人, 川畑篤史

    次世代を担う創薬・医療薬理シンポジウムプログラム・要旨集   2015  2015年

    J-GLOBAL

  • SMP30を欠損したLeprdb/dbマウスはsmall dense LDLが高く脂肪肝になる

    近藤嘉高, 長谷川剛二, 千丸貴史, 福井道明, 中村直登, 丸山直記, 尾林博, 尾林博, 石神昭人

    基礎老化研究   39 ( 2 )  2015年

    J-GLOBAL

  • 閉塞性肺疾患モデルマウスを用いた肺病態増悪因子の同定とその治療的応用

    首藤剛, 亀井竣輔, 亀井竣輔, 坂口由起, 松本千鶴, 小野智美, 菅原卓哉, 野原寛文, 野原寛文, 藤川春花, 藤川春花, 丸田かすみ, 中嶋竜之介, スイコ メリーアン, 近藤嘉高, 石神昭人, 甲斐広文, 甲斐広文

    日本生化学会大会(Web)   88th  2015年

    J-GLOBAL

  • ビタミンCの欠損は,慢性閉塞性肺疾患モデルマウスにおける呼吸機能低下や肺気腫病態を悪化させる

    首藤剛, 坂口由起, 野原寛文, 野原寛文, 亀井竣輔, 亀井竣輔, 藤川春花, 近藤嘉高, SUICO Mary Ann, 石神昭人, 甲斐広文, 甲斐広文

    日本薬学会年会要旨集(CD-ROM)   135th  2015年

    J-GLOBAL

  • アスコルビン酸による光老化予防

    近藤嘉高, 石神昭人

    太陽紫外線防御研究委員会シンポジウム講演要旨集   24th  2014年

    J-GLOBAL

  • ビタミンC生合成不全マウスにおける社会的環境の違いによるストレス応答の差異

    小泉美和子, 近藤嘉高, 伊坂亜友美, 石神昭人, 鈴木恵美

    日本栄養・食糧学会大会講演要旨集   68th  2014年

    J-GLOBAL

  • ストレス調節におけるビタミンCの働き

    小泉美和子, 近藤嘉高, 伊坂亜友美, 石神昭人, 鈴木恵美子

    ビタミン   88 ( 9 )  2014年

    J-GLOBAL

  • Cav3.2T型Ca2+チャネルを阻害するascorbic acidの欠乏は硫化水素による体性痛・内臓痛およびpaclitaxel誘起神経障害性疼痛を増強する

    上坊健太, 三木好輝, 坪田真帆, 関口富美子, 近藤嘉高, 高橋経太, 増富裕文, 石神昭人, 川畑篤史

    日本薬理学会近畿部会プログラム・要旨集   125th  2014年

    J-GLOBAL

  • 脂質代謝異常と加齢指標タンパク質30(SMP30)

    石神昭人, 近藤嘉高

    日本抗加齢医学会総会プログラム・抄録集   14th  2014年

    J-GLOBAL

  • アスコルビン酸による光老化予防

    近藤嘉高, 石神昭人

    太陽紫外線防御研究委員会学術報告   24 ( 1 )  2014年

    J-GLOBAL

  • 社会的環境において惹起される抑うつ様行動に対するビタミンCの働き

    小泉美和子, 近藤嘉高, 伊坂亜友美, 石神昭人, 鈴木恵美子

    ビタミン   88 ( 4 )  2014年

    J-GLOBAL

  • 閉塞性肺疾患モデルマウスにおける内因性ビタミンCの役割

    首藤剛, 坂口由起, 野原寛文, 野原寛文, 亀井竣輔, 亀井竣輔, 藤川春花, 近藤嘉高, SUICO Mary Ann, 石神昭人, 甲斐広文, 甲斐広文

    日本薬理学会西南部会プログラム/抄録集   67th  2014年

    J-GLOBAL

  • マウスにおけるCav3.2T型Ca2+チャネルを介する硫化水素の痛み促進効果はアスコルビン酸欠乏により増大する:SMP30/GNLノックアウトマウスを用いた検討

    上坊健太, 三木好輝, 坪田真帆, 関口富美子, 近藤嘉高, 高橋経太, 増富裕文, 石神昭人, 川畑篤史

    生体機能と創薬シンポジウム要旨集   2013  2013年

    J-GLOBAL

  • Senescence Marker Protein-30欠乏は尿細管間質線維化により糖尿病腎症進展に関与する

    岡田博史, 千丸貴史, 石神昭人, 近藤嘉高, 尾林博, 福井道明, 浅野麻衣, 山崎真裕, 長谷川剛二, 中村直登

    糖尿病   56 ( Supplement 1 )  2013年

    J-GLOBAL

  • ペントースリン酸副経路で働くヒトおよびマウスにおけるグルコン酸キナーゼの同定

    近藤嘉高, 半田節子, 丸山直記, 石神昭人

    日本生化学会大会(Web)   86th  2013年

    J-GLOBAL

  • SMP30を欠損したLeprdb/dbマウスはsmall dense LDLが高く脂肪肝を呈する。

    近藤嘉高, 長谷川剛二, 千丸貴史, 福井道明, 中村直登, 尾林博, 尾林博, 石神昭人

    日本分子生物学会年会プログラム・要旨集(Web)   36th  2013年

    J-GLOBAL

  • ビタミンC欠乏は糖尿病性腎症の尿細管病変の発症に関与する:SMP30KOマウスを用いての検討

    岡田博史, 千丸貴史, 石神昭人, 近藤嘉高, 尾林博, 福井道明, 浅野麻衣, 山崎真裕, 長谷川剛二, 中村直登

    糖尿病   55 ( Supplement 1 )  2012年

    J-GLOBAL

  • ビタミンCを合成できないSMP30/GNLノックアウトマウスを用いたポテトチップスの抗酸化活性評価

    近藤嘉高, 佐久間塁, 市澤恵, 石原克之, 久保美沙子, 半田節子, 麦田裕之, 丸山直記, 古賀秀徳, 石神昭人

    日本栄養・食糧学会大会講演要旨集   66th  2012年

    J-GLOBAL

  • ビタミンC欠乏SMP30/GNLノックアウトマウスへの経口投与によるオリーブオイルポテトチップス「オリービー」の抗酸化活性の評価

    佐久間塁, 近藤嘉高, 市澤恵, 石原克之, 久保美沙子, 半田節子, 麦田裕之, 丸山直記, 古賀秀徳, 石神昭人

    日本農芸化学会大会講演要旨集(Web)   2012  2012年

    J-GLOBAL

  • Insulin Release from Pancreatic Islet in Vitamin C-Deficient Senescence Marker Protein-30/Gluconolactonase Knockout Mice

    Takafumi Senmaru, Goji Hasegawa, Akihito Ishigami, Yoshitaka Kondo, Hiroshi Okada, Mai Asano, Masahiro Yamazaki, Michiaki Fukui, Naoto Nakamura

    DIABETES   60   A540 - A540  2011年07月

    研究発表ペーパー・要旨(国際会議)  

  • マウスビタミンC代謝に対する急性運動の影響

    人見嘉哲, 神林康弘, 石神昭人, 近藤嘉高, 柴田亜樹, 日比野由利, 弘田量二, 木崎節子, 大野英樹, 中村裕之

    日本衛生学雑誌   66 ( 2 )  2011年

    J-GLOBAL

  • ビタミンC欠乏マウスにおける活性酸素種は増加する

    近藤嘉高, 加賀美弥生, 半田節子, 石神昭人, 石神昭人, 丸山直記

    日本栄養・食糧学会大会講演要旨集   65th  2011年

    J-GLOBAL

  • ポテトチップス及び蒸しじゃがいも摂取後の血漿総ビタミンC濃度及び尿中総ビタミンC排泄量に関する検討(速報)

    近藤嘉高, 東千華, 岩間水輝, 石原克之, 半田節子, 丸山直記, 古賀秀徳, 石神昭人, 石神昭人

    ビタミン   85 ( 5/6 )  2011年

    J-GLOBAL

  • 地域在宅高齢女性の運動機能の経年的低下に及ぼす血中ビタミンC濃度の影響

    齋藤京子, 齋藤京子, 吉田英世, 金憲経, 平野浩彦, 島田裕之, 吉田祐子, 岩佐一, 近藤嘉高, 半田節子, 丸山直紀, 石神昭人, 横山徹爾, 鈴木隆雄

    Journal of Epidemiology   21 ( 1 Supplement )  2011年

    J-GLOBAL

  • ビタミンCのインスリン分泌における役割:SMP30/GNLノックアウトマウスを用いての検討

    千丸貴史, 長谷川剛二, 石神昭人, 近藤嘉高, 尾林博, 岡田博史, 浅野麻衣, 山崎真裕, 福井道明, 中村直登

    糖尿病   54 ( Supplement 1 )  2011年

    J-GLOBAL

  • 経口摂取によるじゃがいもおよびポテトチップスに含まれるビタミンCのヒトへの吸収

    東千華, 近藤嘉高, 岩間水輝, 石原克之, 半田節子, 丸山直記, 古賀秀徳, 石神昭人, 石神昭人

    ビタミン   84 ( 4 )  2010年

    J-GLOBAL

  • ヒト経口1回摂取によるポテトチップス及びじゃがいもに含まれるビタミンCの吸収や体内動態に関する検討

    近藤嘉高, 東千華, 岩間水輝, 石原克之, 半田節子, 丸山直記, 古賀秀徳, 石神昭人, 石神昭人

    日本栄養・食糧学会大会講演要旨集   64th  2010年

    J-GLOBAL

  • ヒトにおけるじゃがいもおよびポテトチップスに含まれるビタミンCの吸収

    東千華, 近藤嘉高, 岩間水輝, 石原克之, 半田節子, 丸山直記, 古賀秀徳, 石神昭人, 石神昭人

    日本農芸化学会大会講演要旨集   2010  2010年

    J-GLOBAL

  • ビタミンCが欠乏したSMP30/GNLノックアウトマウスにおける活性酸素種産生能の検討

    近藤嘉高, 加賀美弥生, 半田節子, 丸山直記, 石神昭人, 石神昭人

    ビタミン   84 ( 4 )  2010年

    J-GLOBAL

  • Senescence Marker Protein-30(SMP30)の減少は早期インスリン分泌を障害する

    千丸貴史, 長谷川剛二, 石神昭人, 近藤嘉高, 田中武兵, 山崎真裕, 福井道明, 中村直登

    糖尿病   53 ( Supplement 1 )  2010年

    J-GLOBAL

  • 抗酸化食品因子であるビタミンCの生体内での抗酸化能力

    石神昭人, 近藤嘉高

    日本酸化ストレス学会学術集会プログラム・抄録集   63rd  2010年

    J-GLOBAL

  • ビタミンCが欠乏したSMP30/GNLノックアウトマウスにおける活性酸素種は増加

    近藤嘉高, 加賀美弥生, 半田節子, 石神昭人, 石神昭人, 丸山直記

    生化学    2010年

    J-GLOBAL

  • ビタミンCが欠乏したSMP30/GNLノックアウトマウスにおける活性酸素種産生能は増加する

    近藤嘉高, 加賀美弥生, 半田節子, 丸山直記, 石神昭人, 石神昭人

    基礎老化研究   34 ( 2 )  2010年

    J-GLOBAL

  • マウスの老人性難聴に対するビタミンCの欠乏および補充の影響

    山岨達也, 樫尾明憲, 坂本幸士, 岩村均, 近藤嘉高, 石神昭人, 石神昭人

    日本抗加齢医学会総会プログラム・抄録集   9th  2009年

    J-GLOBAL

  • 高濃度水素溶解水によるスーパーオキシドアニオン増加抑制効果

    佐藤安訓, 近藤嘉高, 天野晶子, 相澤真悟, 半田節子, 石神昭人

    ビタミン   83 ( 4 )  2009年

    J-GLOBAL

  • 産卵鶏における組織中アスコルビン酸およびSMP30レベルに及ぼす誘導換羽の影響

    丸山直記, ニン イーソウ, 近藤嘉高, 石神昭人, 八代田真人, 大谷滋

    基礎老化研究   33 ( 2 )  2009年

    J-GLOBAL

  • 加齢指標蛋白質SMP30の糖代謝における役割

    千丸貴史, 長谷川剛二, 石神昭人, 近藤嘉高, 田中武兵, 浅野麻衣, 川崎真裕, 福井道明, 中村直登

    日本内分泌学会雑誌   85 ( 1 )  2009年

    J-GLOBAL

  • 老化とバイオマーカー (あゆみ 老年医学研究の最前線)

    近藤 嘉高, 石神 昭人, 丸山 直記

    医学のあゆみ   227 ( 8 ) 563 - 566  2008年11月

    CiNii

  • リアルタイムバイオグラフィー法を用いた脳におけるビタミンC活性酸素消去能の検討

    近藤嘉高, 佐々木徹, 佐藤安訓, 天野晶子, 岩間水輝, 丸山直記, 石神昭人

    日本栄養・食糧学会大会講演要旨集   62nd  2008年

    J-GLOBAL

  • ヒト1回摂取によるビタミンC及びアセロラビタミンCの吸収や体内動態に関する検討

    花村高行, 青木仁史, 永峰賢一, 佐藤安訓, 天野晶子, 近藤嘉高, 石神昭人

    ビタミン   82 ( 4 )  2008年

    J-GLOBAL

  • C57BL/6マウスの下顎骨と大腿骨へのビタミンCの影響

    田中愼, 野田万理子, 天野晶子, 岩間水輝, 岸本祐樹, 佐藤安訓, 近藤嘉高, 石神昭人

    基礎老化研究   32 ( 2 )  2008年

    J-GLOBAL

  • カルニチン合成系におけるビタミンCの関与

    古澤元, 古澤元, 佐藤安訓, 佐藤安訓, 近藤嘉高, 佐藤佐多良, 佐藤佐多良, 高橋良哉, 石神昭人

    ビタミン   82 ( 8 )  2008年

    J-GLOBAL

  • アセロラ(Malpighia emarginata DC.)果汁のビタミンC吸収効率に関する検討

    花村高行, 青木仁史, 永峰賢一, 佐藤安訓, 岩間水輝, 天野晶子, 近藤嘉高, 石神昭人

    日本農芸化学会大会講演要旨集   2008  2008年

    J-GLOBAL

  • SMP30/GNLノックアウトマウスを用いたビタミンCの1回摂取による臓器分布の検討

    近藤嘉高, 岩間水輝, 佐藤安訓, 古澤元, 天野晶子, 石神昭人

    ビタミン   82 ( 8 )  2008年

    J-GLOBAL

  • マウス臓器中ビタミンCの加齢変化

    岩間水輝, 岩間水輝, 佐藤安訓, 佐藤安訓, 天野晶子, 近藤嘉高, 岸本祐樹, 岸本祐樹, 町田武生, 石神昭人, 石神昭人

    基礎老化研究   32 ( 2 )  2008年

    J-GLOBAL

  • 脳におけるビタミンCの活性酸素消去能の解析

    近藤嘉高, 佐々木徹, 佐藤安訓, 佐藤安訓, 天野晶子, 岩間水輝, 半田節子, 島田信子, 福田貢, 丸山直記, 石神昭人, 石神昭人

    基礎老化研究   32 ( 2 )  2008年

    J-GLOBAL

  • ヒトでの1回摂取によるビタミンCの血中移行,尿中排泄の検討

    石神昭人, 佐藤安訓, 岩間水輝, 天野晶子, 近藤嘉高

    ビタミン   82 ( 8 )  2008年

    J-GLOBAL

  • C57BL/6マウスの下顎骨と大腿骨の骨性状

    田中愼, 野田万理子, 天野晶子, 岩間水輝, 岸本祐樹, 佐藤安訓, 近藤嘉高, 石神昭人

    基礎老化研究   32 ( 2 )  2008年

    J-GLOBAL

  • ヒト経口1回摂取によるビタミンC及びアセロラビタミンCの吸収や体内動態に関する詳細な検討

    佐藤安訓, 永峰賢一, 花村高行, 青木仁史, 天野晶子, 近藤嘉高, 石神昭人

    日本栄養・食糧学会大会講演要旨集   62nd  2008年

    J-GLOBAL

  • ビタミンC合成不全マウスを用いたビタミンC吸収効率評価系の確立-アセロラはビタミンC吸収効率が良い-

    岩間水輝, 佐藤安訓, 永峰賢一, 花村高行, 青木仁史, 天野晶子, 近藤嘉高, 石神昭人

    日本栄養・食糧学会大会講演要旨集   62nd  2008年

    J-GLOBAL

  • ビタミンCの持つ抗老化作用

    近藤嘉高, 石神昭人, 石神昭人

    日本未病システム学会学術総会抄録集   15th  2008年

    J-GLOBAL

  • 臓器へのビタミンC吸収効率評価系の確立-アセロラパウダーVC30はビタミンC吸収効率が優れている-

    永峰賢一, 花村高行, 青木仁史, 佐藤安訓, 岩間水輝, 天野晶子, 近藤嘉高, 石神昭人

    日本薬学会年会要旨集   128th ( 3 )  2008年

    J-GLOBAL

  • ヒト経口摂取によるビタミンCの血中移行,尿中排泄の詳細な検討

    佐藤安訓, 永峰賢一, 花村高行, 青木仁史, 天野晶子, 近藤嘉高, 石神昭人

    日本薬学会年会要旨集   128th ( 3 )  2008年

    J-GLOBAL

  • 光負荷によるSMP30ノックアウトマウス水晶体の変化

    石川陽平, 橋爪公平, 黒坂大次郎, 手塚優, 岸本成史, 西郡秀夫, 近藤嘉高, 石神昭人, 山本直樹

    日本白内障学会総会/日本眼内レンズ屈折手術学会総会プログラム・講演抄録集   47th-23rd  2008年

    J-GLOBAL

  • SMP30欠損マウスにおける光負荷時の水晶体の変化

    岸本成史, 手塚優, 西郡秀夫, 石川陽平, 橋爪公平, 黒坂大次郎, 近藤嘉高, 石神昭人, 山本直樹

    日本薬学会東北支部大会講演要旨集   47th  2008年

    J-GLOBAL

  • ビタミンC欠乏は脳における活性酸素の生成を増加

    近藤嘉高, 佐々木徹, 佐藤安訓, 佐藤安訓, 天野晶子, 岩間水輝, 半田節子, 島田信子, 福田貢, 丸山直記, 石神昭人, 石神昭人

    生化学    2008年

    J-GLOBAL

  • SMP30/GNLノックアウトマウスを用いたビタミンC吸収効率評価系の確立

    岩間水輝, 佐藤安訓, 永峰賢一, 花村高行, 青木仁史, 天野晶子, 近藤嘉高, 石神昭人

    ビタミン   82 ( 4 )  2008年

    J-GLOBAL

  • SMP-30ノックアウトマウスの下顎骨と大腿骨の骨性状

    田中愼, 野田万理子, 天野晶子, 岩間水輝, 岸本祐樹, 佐藤安訓, 近藤嘉高, 石神昭人

    基礎老化研究   32 ( 2 )  2008年

    J-GLOBAL

  • ビタミンC欠乏は皮膚のコラーゲン含量を減少させる

    新井浩司, 工藤千香子, 土屋博之, 佐藤安訓, 近藤嘉高, 野村義宏, 石神昭人, 西山敏夫

    日本結合組織学会学術大会抄録集   40th  2008年

    J-GLOBAL

  • 脳におけるビタミンCの活性酸素消去能の検討

    近藤嘉高, 佐々木徹, 佐藤安訓, 佐藤安訓, 天野晶子, 岩間水輝, 半田節子, 島田信子, 福田貢, 丸山直記, 石神昭人, 石神昭人

    ビタミン   82 ( 4 )  2008年

    J-GLOBAL

  • ヒト赤血球ではstomatinがGlut1と結合することによりデヒドロアスコルビン酸を取り込む

    近藤嘉高, 石神昭人

    ビタミン   82 ( 9 )  2008年

    J-GLOBAL

  • ビタミンC生合成経路で働く酵素グルコノラクトナーゼ(SMP30/GNL)の加齢変化

    天野晶子, 天野晶子, 近藤嘉高, 岩間水輝, 佐藤安訓, 半田節子, 相垣敏郎, 石神昭人

    日本栄養・食糧学会大会講演要旨集   62nd  2008年

    J-GLOBAL

  • ビタミンC不足は脳における活性酸素を増加する-ビタミンCを合成できないSMP30/GNLノックアウトマウスを用いた解析-

    近藤嘉高, 石神昭人, 石神昭人

    ビタミン   82 ( 12 )  2008年

    J-GLOBAL

  • マウス肝臓におけるSMP30/GNLの組織学的加齢変化

    半田節子, 島田信子, 天野晶子, 天野晶子, 福田貢, 近藤嘉高, 丸山直記, 石神昭人, 石神昭人

    生化学    2008年

    J-GLOBAL

  • ビタミンC欠乏による肝臓での酸化ストレスの解析

    佐藤安訓, 佐藤安訓, 岸本祐樹, 天野晶子, 岩間水輝, 近藤嘉高, 高橋良哉, 石神昭人, 石神昭人

    ビタミン   82 ( 4 )  2008年

    J-GLOBAL

  • 老化マーカータンパク質SMP30はヒト扁平上皮ガンにおけるアポトーシス促進因子である。

    石堂一巳, 宮内梨早, 高橋昌江, 熊坂利夫, 三谷恵子, 近藤嘉高, 石神昭人, 丸山直記, 勝沼信彦

    生化学    2008年

    J-GLOBAL

  • ビタミンC不足は慢性閉塞性肺疾患の発症リスクを高める

    石神昭人, 佐藤匡, 佐藤安訓, 近藤嘉高, 瀬山邦明, 丸山直記

    ビタミン   81 ( 4 )  2007年

    J-GLOBAL

  • ビタミンCの不足は慢性閉塞性肺疾患(COPD)発症リスクを高める

    石神昭人, 佐藤匡, 佐藤安訓, 近藤嘉高, 瀬山邦明, 丸山直記

    日本栄養・食糧学会大会講演要旨集   61st  2007年

    J-GLOBAL

  • ビタミンCの不足は老化を加速する

    近藤嘉高, 佐藤安訓, 井内陽子, 錦見盛光, 丸山直記, 石神昭人

    日本栄養・食糧学会大会講演要旨集   61st  2007年

    J-GLOBAL

  • 高等動物の2つのアスコルビン酸合成経路

    井内陽子, 近藤嘉高, 石神昭人, 錦見盛光

    ビタミン   81 ( 4 )  2007年

    J-GLOBAL

  • グルコノラクトナーゼ活性は加齢で低下する

    近藤嘉高, 近藤嘉高, 井内陽子, 岩佐嘉洋, 岩佐嘉洋, 島田信子, 福田貢, 下門顕太郎, 錦見盛光, 丸山直記, 石神昭人

    ビタミン   81 ( 4 )  2007年

    J-GLOBAL

  • ビタミンC合成不全マウスを用いたin vivoビタミンC抗酸化能の検討

    天野晶子, 天野晶子, 天野晶子, 近藤嘉高, 佐藤安訓, 町田武夫, 相垣敏郎, 丸山直記, 石神昭人

    生化学    2007年

    J-GLOBAL

  • SMP30ノックアウトマウスを用いたビタミンC抗酸化能力の検討

    天野晶子, 天野晶子, 天野晶子, 近藤嘉高, 佐藤安訓, 町田武生, 相垣敏郎, 丸山直記, 石神昭人

    基礎老化研究   31 ( 2 )  2007年

    J-GLOBAL

  • ビタミンC不足は老化を加速

    石神昭人, 佐藤安訓, 近藤嘉高, 古澤元, 天野晶子, 島田信子, 福田貢, 半田節子, 久保幸穂, 丸山直記

    日本薬学会年会要旨集   127th ( 2 )  2007年

    J-GLOBAL

  • グルコノラクトナーゼ活性は加齢で低下する

    近藤嘉高, 近藤嘉高, 岩佐嘉洋, 岩佐嘉洋, 島田信子, 福田貢, 下門顕太郎, 丸山直記, 石神昭人

    基礎老化研究   30 ( 2 )  2006年

    J-GLOBAL

  • グルコノラクトナーゼ活性は加齢で低下する

    近藤嘉高, 近藤嘉高, 岩佐嘉洋, 岩佐嘉洋, 島田信子, 福田貢, 下門顕太郎, 丸山直記, 石神昭人

    基礎老化研究   30 ( 2 )  2006年

    J-GLOBAL

  • SMP30ノックアウトマウス-ビタミンC欠乏,壊血病モデルマウス-

    石神昭人, 佐藤安訓, 佐藤安訓, 井内陽子, 近藤嘉高, 半田節子, 久保幸穂, 後藤佐多良, 錦見盛光, 丸山直記

    日本薬学会年会要旨集   126th ( 2 )  2006年

    J-GLOBAL

  • ラットグルコノラクトナーゼのSMP30としての同定 (続報)

    近藤嘉高, 佐藤安訓, 井内陽子, 錦見盛光, 丸山直記, 石神昭人

    ビタミン   80 ( 5/6 )  2006年

    J-GLOBAL

  • [Molecular abnormality in aging: its contribution to clinical pathology].

    Maruyama N, Ishigami A, Kondo Y

    Rinsho byori. The Japanese journal of clinical pathology   53   728 - 734  2005年08月  [査読有り]

    PubMed

  • SMP30はグルコノラクトナーゼである

    近藤嘉高, 石神昭人, 下門顕太郎, 丸山直記

    基礎老化研究   29 ( 2 )  2005年

    J-GLOBAL

  • SMP30は肝臓で唯一のDFPaseである

    近藤嘉高, 石神昭人, 下門顕太郎, 丸山直記

    基礎老化研究   28 ( 2 )  2004年

    J-GLOBAL

  • SMP30の抗老化作用と分子機能の検討

    近藤嘉高, 石神昭人, 下門顕太郎, 丸山直記

    基礎老化研究   28 ( 4 )  2004年

    J-GLOBAL

  • SMP30が持つ有機リン分解酵素活性の検証

    石神昭人, 近藤嘉高, ま冬芸, 倉元雅史, 下門顕太郎, 丸山直記

    日本薬学会年会要旨集   123rd ( 3 )  2003年

    J-GLOBAL

▼全件表示

受賞

  • 平成25年度 研究奨励理事長賞

    2013年06月   東京都健康長寿医療センター研究所   Smp30/Sod1ダブルノックアウトマウスを用いた非アルコール性脂肪肝(NAFLD)発症機序の解明  

    受賞者: 近藤嘉高

  • 第15回日本未病システム学会 優秀演題賞

    2008年11月   日本未病システム学会   ビタミンCの持つ抗老化作用  

    受賞者: 近藤嘉高

  • 論文賞

    2007年12月   ネスレ栄養科学会議   Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy  

    受賞者: 近藤嘉高

  • 助成論文 優秀論文賞

    2005年02月   財団法人博慈会老年病研究所   Senescence marker protein-30 is a unique enzyme that hydrolyzes diisopropyl phosphorofluoridate (DFP) in the liver  

    受賞者: 近藤嘉高

  • 若手奨励賞

    2003年06月   日本基礎老化学会  

    受賞者: 近藤嘉高

共同研究・競争的資金等の研究課題

  • ビタミンC、Eの同時不足がエストロゲン欠乏マウスの皮膚に及ぼす影響

    日本学術振興会  科学研究費助成事業 若手研究(B)

    研究期間:

    2016年04月
    -
    2019年03月
     

    近藤 嘉高

     概要を見る

    本研究は、青壮年期の女性(エストロゲン充分)や更年期以降の女性(エストロゲン欠乏)の皮膚におけるVC不足, VE不足, 2重(同時)不足が紫外線による皮膚の黒化やシワの形成(光老化)に及ぼす影響を明らかにすることを目的とした。ビタミンCを体内で合成できないSMP30ノックアウト(KO)マウスと、エストロゲンを合成できないAromatase(Ar)-KOマウス、ヘアレスマウスを掛け合わせて、SMP30/Arダブルノックアウト(DKO)ヘアレスマウスを作出した。しかし、繁殖成績が悪く、実験に必要な匹数が得られなかった。今後は、SMP30-KOヘアレスマウスの卵巣摘出モデルに切り換えるべきである。

  • microRNAによる新しいCOPD治療を目指した気道分泌型エクソソーム解析

    公益財団法人喫煙科学研究財団 

    研究期間:

    2017年04月
    -
    2019年03月
     

    近藤嘉高

  • ヒト培養表皮におけるアスコルビン酸の経皮吸収および紫外線UVBによる細胞障害に対する予防、回復効果の検討

    公益財団法人コスメトロジー研究振興財団 

    研究期間:

    2016年04月
    -
    2017年10月
     

    近藤嘉高

  • 動物におけるペントースリン酸副経路の同定

    日本学術振興会  科学研究費助成事業 若手研究(B)

    研究期間:

    2011年
    -
    2013年
     

    近藤 嘉高

     概要を見る

    ペントースリン酸経路は、グルコース6-リン酸をグルコノラクトン6-リン酸、グルコン酸6-リン酸を経て、グリセルアルデヒド3-リン酸に代謝し、NADPHおよび核酸原料の供給を担う。細菌類では、グルコースからグルコノラクトン、グルコン酸を経て、グルコン酸6-リン酸に至る副経路が知られている。しかし、動物において副経路が存在するかどうかは不明である。本研究では、ヒトおよびマウスにおいてグルコン酸をグルコン酸6-リン酸にリン酸化するグルコン酸キナーゼの遺伝子を同定した。

  • ビタミンC合成不全マウスを用いた機能性食品の抗酸化能評価システムの開発

    日本学術振興会  科学研究費助成事業 若手研究(スタートアップ)

    研究期間:

    2008年
    -
    2009年
     

    近藤 嘉高

     概要を見る

    ビタミンCを合成できないSMP30/GNLノックアウトマウスは、活性酸素種(ROS)の産生が亢進するかどうか、機能性食品の抗酸化能を評価できるかどうかを検討した。VC欠乏マウスの全身組織におけるROS産生は、顕著に増加した。また、ROS消去能をもつ水素水の投与は、VC欠乏マウスの脳におけるROS産生を抑制した。本研究から、VC欠乏マウスを用いた機能性食品の抗酸化能評価システムが確立された。

  • 加齢指標蛋白質SMP30が関与する動脈硬化発症機序の解明

    日本学術振興会  科学研究費助成事業 特別研究員奨励費

    研究期間:

    2006年
    -
    2007年
     

    近藤 嘉高

     概要を見る

    加齢指標蛋白質SMP30はビタミンC生合成経路の酵素グルコノラクトナーゼであり、SMP30ノックアウト(SMP30-K0)マウスは臓器中および血漿中ビタミンC含量が顕著に低下する(PNAS,2006)。前年度の研究において、ApoE/SMP30ダブルノックアウトマウスは、体内のビタミンC量が枯渇しており、動脈硬化巣の形成が抑制されることを明らかにした。また、SMP30-K0マウスの肝臓において脂質の蓄積が認められたことから、ビタミンC不足は脂質代謝異常をもたらす可能性が示唆された。ビタミンCは、脂肪酸代謝に必要なL-カルニチンの生合成経路において、6-N-トリメチルリシンジオキシゲナーゼおよびγ-ブチロベタインジオキシゲナーゼの酵素反応に必須であるといわれている。しかし、L-カルニチン生合成にビタミンCが必須か否か今まではっきりとした結論が出ていない。本研究では、SMP30-K0マウスを用いて、生体内でのビタミンC欠乏がカルニチン生合成に影響を与えるかどうかを検討した。即ち、SMP30-K0マウスをビタミンCおよびカルニチン欠乏飼料を与えて飼育し、ビタミンC欠乏状態にさせた。しかし、SMP30-K0マウスの体内カルニチン含量は減少しなかった。また、尿中へのカルニチン排泄量に変化は認められなかった。以上の結果から、生体内におけるカルニチン生合成にビタミンCが必須ではないことが示された。さらに、ビタミンCを欠乏させた肝臓ホモジネートを用いたin vitro実験から、ビタミンCがなくてもカルニチンは合成されることが明らかとなった。グルタチオンなどビタミンC以外の還元物質が代償性に働いている可能性が考えられる。本研究により、カルニチン生合成にビタミンCが必須ではないと結論づけられた。従って、ビタミンCの不足はカルニチンが関与しない機序により脂質代謝異常を引き起こすと考えられる。

▼全件表示

特定課題研究

  • マウスにおけるグルコン酸キナーゼおよびグルコノラクトナーゼの免疫組織化学的研究

    2021年  

     概要を見る

    Pentose phosphate pathway (PPP) produce NADPH which is utilized for fatty acid synthesis, cholesterol synthesis, and steroid biosynthesis, and redox maintenance, and ribose 5-phosphate which is necessary for synthesis of nucleic acid. It is known that alternative pathway of PPP from glucose to 6-phosphogluconate exists in bacteria, however, it remains unclear in animals. In our previous study, SMP30/gluconolactonase (GNL) hydrolyzed glucono 1,5-lactone to gluconate, and gluconokinase (GNK) catalyzed phosphorylation of gluconate to 6-phosphogluconate in human and mouse. To reveal tissue distribution of GNK in mouse, we measured protein levels of SMP30/GNL and GNK in alternative PPP, and glucose 6-phosphate dehydrogenase (G6PD) in PPP.Six C57BL/6J male mice were dissected at 8 weeks of age, and 19 kinds of tissues were collected. Protein levels of SMP30/GNL, GNK, and G6PD were quantified by Western blot analysis.Both of SMP30/GNL and GNK protein was highly expressed in liver, duodenum, and kidney. G6PD protein was highly expressed in epididymal fat, subcutaneous fat, adrenal gland, and brown fat. Overall, the tissue distributions of protein level were similar between SMP30/GNL and GNK, which was distinct from that of G6PD. These results suggest that SMP30/GNL and GNK could cooperatively functions in alternative PPP, and physiological role of alternative PPP might be different from that of PPP. Immunohistochemical staining of SMP30/GNL, GNK, and G6PD in tissues are now in progress.

  • 新規ペントースリン酸経路で働くグルコン酸キナーゼのマウスにおける発現解析

    2020年  

     概要を見る

    Pentose phosphate pathway (PPP) produce NADPH which is utilized for fatty acid synthesis, cholesterol synthesis, and steroid biosynthesis, and redox maintenance, and ribose 5-phosphate which is necessary for synthesis of nucleic acid. It is known that alternative pathway of PPP from glucose to 6-phosphogluconate exists in bacteria, however, it remains unclear in animals. In our previous study, SMP30/gluconolactonase (GNL) hydrolyzed glucono 1,5-lactone to gluconate, and gluconokinase (GNK) catalyzed phosphorylation of gluconate to 6-phosphogluconate in human and mouse. To reveal tissue distribution of GNK in mouse, we measured gene expression levels of GNK, and compared with those of SMP30/GNL, glucose 6-phosphate dehydrogenase (G6PD), and 6-phosphogluconolactonase (6PGL).Six C57BL/6J male mice were dissected at 8 weeks of age, and 20 kinds of tissues were collected. Gene expression levels of GNK, SMP30/GNL, G6PD, and 6PGL were quantified by using real-time PCR. GNK, SMP30/GNL, G6PD and 6PGL genes were ubiquitously expressed in almost all tissues. GNK gene was highly expressed in liver, kidney, duodenum, and brown fat. Gene expression of SMP30/GNL was most abundant in liver, subsequently in kidney, duodenum, and adrenal gland. G6PD gene was highly expressed in epididymal fat, brown fat, adrenal gland, and testis. 6PGL gene showed higher expression in brown fat and testis.Overall, tissue distribution of GNK gene expression showed similarity to that of SMP30/GNL, which is distinct from those of G6PD and 6PGL. These results suggest that GNK and SMP30/GNL could cooperatively functions in alternative PPP.

  • 動物におけるペントースリン酸副経路の同定

    2020年  

     概要を見る

    Pentose phosphate pathway (PPP) produce NADPH which is utilized for fatty acid synthesis, cholesterol synthesis, and steroid biosynthesis, and redox maintenance, and ribose 5-phosphate which is necessary for synthesis of nucleic acid. It is known that alternative pathway of PPP from glucose to 6-phosphogluconate exists in bacteria, however, it remains unclear in animals. In our previous study, SMP30/gluconolactonase (GNL) hydrolyzed glucono 1,5-lactone to gluconate. To reveal a novel alternative PPP, we identified gluconokinase (GNK) gene and characterized GNK activity for phosphorylating gluconate to 6-phosphogluconate.&nbsp;To reveal tissue distribution of GNK in mouse, we measured gene expression levels of GNK, and compared with those of SMP30/GNL, glucose 6-phosphate dehydrogenase (G6PD), and 6-phosphogluconolactonase (6PGL). Six C57BL/6J male mice were dissected at 8 weeks of age, and 20 kinds of tissues were collected. Gene expression levels of GNK, SMP30/GNL, G6PD, and 6PGL were quantified by using real-time PCR. GNK, SMP30/GNL, G6PD and 6PGL genes were ubiquitously expressed in almost all tissues. GNK gene was highly expressed in liver, kidney, duodenum, and brown fat. Gene expression of SMP30/GNL was most abundant in liver, subsequently in kidney, duodenum, and adrenal gland. G6PD gene was highly expressed in epididymal fat, brown fat, adrenal gland, and testis. 6PGL gene showed higher expression in brown fat and testis.&nbsp;Overall, tissue distribution of GNK gene expression showed similarity to that of SMP30/GNL, which is distinct from those of G6PD and 6PGL. These results suggest that GNK and SMP30/GNL could cooperatively functions in alternative PPP.

  • 動物におけるペントースリン酸副経路の同定

    2020年  

     概要を見る

    Pentose phosphate pathway (PPP) produce NADPH which is utilized for fatty acid synthesis, cholesterol synthesis, and steroid biosynthesis, and redox maintenance, and ribose 5-phosphate which is necessary for synthesis of nucleic acid. It is known that alternative pathway of PPP from glucose to 6-phosphogluconate exists in bacteria, however, it remains unclear in animals. In our previous study, SMP30/gluconolactonase (GNL) hydrolyzed glucono 1,5-lactone to gluconate, and gluconokinase (GNK) catalyzed phosphorylation of gluconate to 6-phosphogluconate in human and mouse. To reveal tissue distribution of GNK in mouse, we measured gene expression levels of GNK, and compared with those of SMP30/GNL, glucose 6-phosphate dehydrogenase (G6PD), and 6-phosphogluconolactonase (6PGL).Six C57BL/6J male mice were dissected at 8 weeks of age, and 20 kinds of tissues were collected. Gene expression levels of GNK, SMP30/GNL, G6PD, and 6PGL were quantified by using real-time PCR. GNK, SMP30/GNL, G6PD and 6PGL genes were ubiquitously expressed in almost all tissues. GNK gene was highly expressed in liver, kidney, duodenum, and brown fat. Gene expression of SMP30/GNL was most abundant in liver, subsequently in kidney, duodenum, and adrenal gland. G6PD gene was highly expressed in epididymal fat, brown fat, adrenal gland, and testis. 6PGL gene showed higher expression in brown fat and testis.Overall, tissue distribution of GNK gene expression showed similarity to that of SMP30/GNL, which is distinct from those of G6PD and 6PGL. These results suggest that GNK and SMP30/GNL could cooperatively functions in alternative PPP.

  • 動物におけるペストースリン酸副経路の同定

    2019年  

     概要を見る

    Pentose phosphate pathway (PPP) is a metabolic pathway parallel to glycolysis, which generates nicotinamide adenine dinucleotide phosphate (NADPH) for reductive biosynthesis reactions and pentoses as well as such as ribose 5-phosphate, a precursor for the synthesis of nucleotides. 6-phosphogluconate is an intermediate in PPP which metabolize glucose 6-phosphate to glyceraldehyde 3-phosphate. In bacteria, it is known that alternative pathway of PPP metabolize glucose to 6-phosphogluconate. However, it has not been reported in human and mouse. To reveal a novel alternative PPP, we identified gluconokinase (GNK) gene and characterized GNK activity for phosphorylating gluconte to 6-phosphogluconate.By NCBI-BLAST search, amino acid sequence of bacterial GNK in&nbsp;Pseudomonas putida&nbsp;KT2440&nbsp;showed high homology with those of possible GNK gene (NM_001001551 and NM_198004) in human and mouse, respectively. We cloned cDNA of possible GNK gene from liver in human and mouse. Recombinant 6xHis-tagged proteins were purified from bacterial soluble fraction by using Ni-NTA agarose and DEAE-Sephacel column. GNK activity in reaction mixture containng gluconate, ATP, MgCl2, and recombinant GNK protein was measured by monitoring A340&nbsp;of NADPH generated in coupled with resulting 6-phosphogluconate, NADP+, and 6-phosphogluconate dehydrogenase. Human and mouse recombinat proteins showed GNK activity in dose-dependent manner, respectively. Furthermore, GNK activity was detected in mouse liver extract.In this study, we identified GNK gene in human and mouse, suggesting that alternative PPP could exists in human and mouse.

  • 動物におけるペントースリン酸副経路の同定

    2019年  

     概要を見る

    Pentose phosphate pathway (PPP) is a metabolic pathway parallel to glycolysis, which generates nicotinamide adenine dinucleotide phosphate (NADPH) for reductive biosynthesis reactions and pentoses as well as such as ribose 5-phosphate, a precursor for the synthesis of nucleotides. 6-phosphogluconate is an intermediate in PPP which metabolize glucose 6-phosphate to glyceraldehyde 3-phosphate. In bacteria, it is known that alternative pathway of PPP metabolize glucose to 6-phosphogluconate. However, it has not been reported in human and mouse. To reveal a novel alternative PPP, we identified gluconokinase (GNK) gene and characterized GNK activity for phosphorylating gluconte to 6-phosphogluconate.By NCBI-BLAST search, amino acid sequence of bacterial GNK in Pseudomonas putida KT2440 showed high homology with those of possible GNK gene (NM_001001551 and NM_198004) in human and mouse, respectively. We cloned cDNA of possible GNK gene from liver in human and mouse. Recombinant 6xHis-tagged proteins were purified from bacterial soluble fraction by using Ni-NTA agarose and DEAE-Sephacel column. GNK activity in reaction mixture containng gluconate, ATP, MgCl2, and recombinant GNK protein was measured by monitoring A340 of NADPH generated in coupled with resulting 6-phosphogluconate, NADP+, and 6-phosphogluconate dehydrogenase. Human and mouse recombinat proteins showed GNK activity in dose-dependent manner, respectively. Furthermore, GNK activity was detected in mouse liver extract.In this study, we identified GNK gene in human and mouse, suggesting that alternative PPP could exists in human and mouse.

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委員歴

  • 2017年04月
    -
    継続中

    日本基礎老化学会  評議員

  • 2012年04月
    -
    2014年03月

    日本基礎老化学会  評議員・編集委員