KONDO, Yoshitaka

写真a

Affiliation

Faculty of Human Sciences, School of Human Sciences

Job title

Assistant Professor(without tenure)

Homepage URL

https://www.waseda.jp/fhum/

Education 【 display / non-display

  • 2004.04
    -
    2007.03

    Tokyo Medical and Dental University  

  • 2002.04
    -
    2004.03

    Tokyo Medical and Dental University  

  • 1998.04
    -
    2002.03

    Waseda University   School of Education  

Degree 【 display / non-display

  • 東京医科歯科大学   博士(医学)

Research Experience 【 display / non-display

  • 2019.04
    -
    Now

    Waseda University   Faculty of Human Sciences   Assistant Professor

  • 2016.04
    -
    2019.03

    Tokyo Metropolitan Institute of Gerontology (TMIG)

  • 2014.04
    -
    2016.03

    Toho University

  • 2009.04
    -
    2014.03

    Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology   Tokyo Metropolitan Institute of Gerontology (TMIG)

  • 2008.04
    -
    2009.03

    Tokyo Metropolitan Institute of Gerontology (TMIG)

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Professional Memberships 【 display / non-display

  • 2015.06
    -
    Now

    日本老年医学会

  • 2014.09
    -
    Now

    日本免疫学会

  • 2013.08
    -
    Now

    日本分子生物学会

  • 2008.07
    -
    Now

    日本未病システム学会

  • 2007.02
    -
    Now

    日本栄養・食糧学会

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Research Areas 【 display / non-display

  • Molecular biology

  • Functional biochemistry

  • Experimental pathology

  • Metabolism and endocrinology

  • Nutrition science and health science

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Research Interests 【 display / non-display

  • カロリー制限

  • 健康長寿

  • 栄養

  • ノックアウトマウス

  • SMP30

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Papers 【 display / non-display

  • 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  2020.12  [International journal]

     View Summary

    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  2020.07  [International journal]

     View Summary

    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  2020.05  [International journal]

     View Summary

    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  2020.03  [Domestic journal]

     View Summary

    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  [Domestic journal]

     View Summary

    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

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Misc 【 display / non-display

  • [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  2005.08  [Refereed]

    PubMed

Awards 【 display / non-display

  • 平成25年度 研究奨励理事長賞

    2013.06   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

    Winner: 近藤嘉高

  • 第15回日本未病システム学会 優秀演題賞

    2008.11   日本未病システム学会   ビタミンCの持つ抗老化作用

    Winner: 近藤嘉高

  • 論文賞

    2007.12   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

    Winner: 近藤嘉高

  • 助成論文 優秀論文賞

    2005.02   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

    Winner: 近藤嘉高

  • 若手奨励賞

    2003.06   日本基礎老化学会  

    Winner: 近藤嘉高

Research Projects 【 display / non-display

  • Effect of vitamin C and vitamin E deficiency on skin of estrogen-deficient female mice

    Grant-in-Aid for Young Scientists (B)

    Project Year :

    2016.04
    -
    2019.03
     

    Kondo Yoshitaka

     View Summary

    To clarify the effect of vitamin C and vitamin E deficiency on skin of estrogen-deficient mice, we generated SMP30/Aromatase-double knockout mice which are not able to synthesize vitamin C, vitamin E, and estrogen. However, we could not gain sufficient numbers of SMP30/Aromatase-double knockout mice for further experiments.

  • 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

    Project Year :

    2017.04
    -
    2019.03
     

    近藤嘉高

    Authorship: Principal investigator

  • 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

    Project Year :

    2016.04
    -
    2017.10
     

    近藤嘉高

    Authorship: Principal investigator

  • Identification of alternative pentose phosphate pathway in animals.

    Grant-in-Aid for Young Scientists (B)

    Project Year :

    2011
    -
    2013
     

    KONDO Yoshitaka

    Authorship: Principal investigator

     View Summary

    In pentose phosphate pathway, glucose 6-phosphate is converted to glyceraldehyde 3-phosphate via glucono-1,5-lactone 6-phosphate and 6-phospho gluconate to produce NADPH and various hexose which is necessary for a synthesis of nucleic acid. It is known that alternative pathway from glucose to 6-phospho gluconate through gluconolactone and gluconate exists in bacteria. However, it remains unclear whether the alternative pathway exists in animals. In this study, we identified the gluconokinase gene which catalyzes a phosphorylation of gluconate to 6-phospho gluconate in human and mouse.

  • Evaluation of antioxidant capability in functional foods by using vitamin C-depleted mice.

    Grant-in-Aid for Young Scientists (Start-up)

    Project Year :

    2008
    -
    2009
     

    KONDO Yoshitaka

    Authorship: Principal investigator

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Specific Research 【 display / non-display

  • 動物におけるペントースリン酸副経路の同定

    2020  

     View Summary

    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. 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  

     View Summary

    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.

  • 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  

     View Summary

    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  

     View Summary

    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.

  • 動物におけるペントースリン酸副経路の同定

    2019  

     View Summary

    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.

 

Syllabus 【 display / non-display

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Committee Memberships 【 display / non-display

  • 2017.04
    -
    Now

    日本基礎老化学会  評議員

  • 2012.04
    -
    2014.03

    日本基礎老化学会  評議員・編集委員