2023/10/03 更新

写真a

ナカムラ フミアキ
中村 文彬
所属
理工学術院 大学院先進理工学研究科
職名
助教
学位
博士(理学) ( 2023年03月 早稲田大学 )

研究キーワード

  • 天然物化学

 

論文

  • Two Onnamide Analogs from the Marine Sponge Theonella conica: Evaluation of Geometric Effects in the Polyene Systems on Biological Activity

    Fumiaki Nakamura, Hiroshi Kimura, Nobuhiro Fusetani, Yoichi Nakao

    Molecules    2023年03月

    DOI

    Scopus

    1
    被引用数
    (Scopus)
  • Coronarin D, a Metabolite from the Wild Turmeric, Curcuma aromatica, Promotes the Differentiation of Neural Stem Cells into Astrocytes.

    Satoshi Otsuka, Midori Kawamura, Shutaro Fujino, Fumiaki Nakamura, Daisuke Arai, Nobuhiro Fusetani, Yoichi Nakao

    Journal of agricultural and food chemistry   70 ( 10 ) 3300 - 3309  2022年03月  [国際誌]

     概要を見る

    Plants in the genus Curcuma have been widely used as traditional medicines in Asian countries. These plants contain bioactive compounds with neuroprotective properties or activities that increase neural stem cells (NSCs) and neurons. However, bioactive components in Curcuma that promote the differentiation of NSCs into astrocytes have not yet been reported. Here, the effects of Curcuma extracts on the in vitro differentiation of embryonic stem-cell-derived NSCs were evaluated. The extract of the wild turmeric, Curcuma aromatica, strongly promoted the differentiation of NSCs into astrocytes. Bioassay-guided isolation yielded coronarins C (1) and D (2), as well as (E)-labda-8(17),12-diene-15,16-dial (3) as the bioactive compounds. Coronarin D (2) markedly promoted the differentiation of NSCs into astrocytes up to approximately 4 times (3.64 ± 0.48) and increased the expression level of GFAP at the mRNA and protein level, while compounds 1 and 3 exhibited only weak effects, suggesting that the 15-hydroxy-Δ12-γ-lactone moiety is important for bioactivity. Moreover, compound 2 increased the number of pSTAT3-positive cells, suggesting that compound 2 promoted astrocytic differentiation through JAK/STAT signaling pathway.

    DOI PubMed

    Scopus

    4
    被引用数
    (Scopus)
  • Marine Pharmacology in 2016-2017: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

    Alejandro M S Mayer, Aimee J Guerrero, Abimael D Rodríguez, Orazio Taglialatela-Scafati, Fumiaki Nakamura, Nobuhiro Fusetani

    Marine drugs   19 ( 2 )  2021年01月  [国際誌]

     概要を見る

    The review of the 2016-2017 marine pharmacology literature was prepared in a manner similar as the 10 prior reviews of this series. Preclinical marine pharmacology research during 2016-2017 assessed 313 marine compounds with novel pharmacology reported by a growing number of investigators from 54 countries. The peer-reviewed literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral activities for 123 marine natural products, 111 marine compounds with antidiabetic and anti-inflammatory activities as well as affecting the immune and nervous system, while in contrast 79 marine compounds displayed miscellaneous mechanisms of action which upon further investigation may contribute to several pharmacological classes. Therefore, in 2016-2017, the preclinical marine natural product pharmacology pipeline generated both novel pharmacology as well as potentially new lead compounds for the growing clinical marine pharmaceutical pipeline, and thus sustained with its contributions the global research for novel and effective therapeutic strategies for multiple disease categories.

    DOI PubMed

  • Histone modification dynamics as revealed by multicolor immunofluorescence-based single-cell analysis.

    Yoko Hayashi-Takanaka, Yuto Kina, Fumiaki Nakamura, Leontine E Becking, Yoichi Nakao, Takahiro Nagase, Naohito Nozaki, Hiroshi Kimura

    Journal of cell science   133 ( 14 )  2020年07月  [国際誌]

     概要を見る

    Post-translational modifications on histones can be stable epigenetic marks or transient signals that can occur in response to internal and external stimuli. Levels of histone modifications fluctuate during the cell cycle and vary among different cell types. Here, we describe a simple system to monitor the levels of multiple histone modifications in single cells by multicolor immunofluorescence using directly labeled modification-specific antibodies. We analyzed histone H3 and H4 modifications during the cell cycle. Levels of active marks, such as acetylation and H3K4 methylation, were increased during the S phase, in association with chromatin duplication. By contrast, levels of some repressive modifications gradually increased during G2 and the next G1 phases. We applied this method to validate the target modifications of various histone demethylases in cells using a transient overexpression system. In extracts of marine organisms, we also screened chemical compounds that affect histone modifications and identified psammaplin A, which was previously reported to inhibit histone deacetylases. Thus, the method presented here is a powerful and convenient tool for analyzing the changes in histone modifications.

    DOI PubMed

    Scopus

    13
    被引用数
    (Scopus)
  • Combinatorial Effects of Soluble, Insoluble, and Organic Extracts from Jerusalem Artichokes on Gut Microbiota in Mice.

    Hiroyuki Sasaki, Yijin Lyu, Yuki Nakayama, Fumiaki Nakamura, Aya Watanabe, Hiroki Miyakawa, Yoichi Nakao, Shigenobu Shibata

    Microorganisms   8 ( 6 )  2020年06月  [国際誌]

     概要を見る

    Jerusalem artichokes contain high amounts of inulin, which is a prebiotic that supports digestive health, as well as a variety of insoluble fibers and caffeoylquinic acid. The individual impact of these components on gut microbiota is well known; however, the combinatorial effects are less clear. In this investigation, we fractionated Jerusalem artichokes into three parts (water-soluble extract, insoluble extract, and organic extract) and powdered them. Mice were fed a high-fat diet that included one or more of these extracts for 10 days, and then their cecal pH, cecal short-chain fatty acids (SCFAs), and fecal microbiota were evaluated. The combination of the water-soluble and organic extract decreased cecal pH and increased the concentration of SCFAs and led to dynamic changes in the composition of the gut microbiota. These results demonstrate that both the water-soluble and organic extracts in Jerusalem artichokes are bioactive substances that are capable of changing SCFA production and the composition of gut microbiota. Powdered Jerusalem artichokes, rather than inulin supplements, may be superior for promoting a healthy gut.

    DOI PubMed

    Scopus

    7
    被引用数
    (Scopus)
  • Marine Pharmacology in 2014-2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

    Alejandro M S Mayer, Aimee J Guerrero, Abimael D Rodríguez, Orazio Taglialatela-Scafati, Fumiaki Nakamura, Nobuhiro Fusetani

    Marine drugs   18 ( 1 )  2019年12月  [国際誌]

     概要を見る

    The systematic review of the marine pharmacology literature from 2014 to 2015 was completed in a manner consistent with the 1998-2013 reviews of this series. Research in marine pharmacology during 2014-2015, which was reported by investigators in 43 countries, described novel findings on the preclinical pharmacology of 301 marine compounds. These observations included antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral, and anthelmintic pharmacological activities for 133 marine natural products, 85 marine compounds with antidiabetic, and anti-inflammatory activities, as well as those that affected the immune and nervous system, and 83 marine compounds that displayed miscellaneous mechanisms of action, and may probably contribute to novel pharmacological classes upon further research. Thus, in 2014-2015, the preclinical marine natural product pharmacology pipeline provided novel pharmacology as well as new lead compounds for the clinical marine pharmaceutical pipeline, and thus continued to contribute to ongoing global research for alternative therapeutic approaches to many disease categories.

    DOI PubMed

    Scopus

    66
    被引用数
    (Scopus)
  • Effect of mycalolides isolated from a marine sponge Mycale aff. nullarosette on actin in living cells.

    Yoko Hayashi-Takanaka, Yuto Kina, Fumiaki Nakamura, Shota Yamazaki, Masahiko Harata, Rob W M van Soest, Hiroshi Kimura, Yoichi Nakao

    Scientific reports   9 ( 1 ) 7540 - 7540  2019年05月  [国際誌]

     概要を見る

    Discovery of novel bioactive compounds is important not only for therapeutic purposes but also for understanding the mechanisms of biological processes. To screen bioactive compounds that affect nuclear morphology in marine organism extracts, we employed a microscopy-based assay using DNA staining of human cancer cells. A crude extract from a marine sponge Mycale aff. nullarosette, collected from the east coast of Japan, induced cellular binucleation. Fractionation of the extract led to the isolation of mycalolides A and B, and 38-hydroxymycalolide B as the active components. Mycalolides have been identified as marine toxins that induce depolymerization of the actin filament. Live cell imaging revealed that low concentrations of mycalolide A produce binucleated cells by inhibiting the completion of cytokinesis. At higher concentrations, however, mycalolide A causes immediate disruption of actin filaments and changes in cell morphology, yielding rounded cells. These results suggest that the completion of cytokinesis is a process requiring high actin polymerization activity. Furthermore, luciferase reporter assays with mycalolide A treatments support the view that the level of globular actin can affect transcription of a serum response gene.

    DOI PubMed

    Scopus

    6
    被引用数
    (Scopus)
  • Kakeromamide A, a new cyclic pentapeptide inducing astrocyte differentiation isolated from the marine cyanobacterium Moorea bouillonii.

    Fumiaki Nakamura, Hiroshi Maejima, Midori Kawamura, Daisuke Arai, Tatsufumi Okino, Meng Zhao, Tao Ye, Jungyeol Lee, Young-Tae Chang, Nobuhiro Fusetani, Yoichi Nakao

    Bioorganic & medicinal chemistry letters   28 ( 12 ) 2206 - 2209  2018年07月  [国際誌]

     概要を見る

    Kakeromamide A (1), a new cyclic pentapeptide encompassing a thiazole ring moiety and a β-amino acid, was isolated from the marine cyanobacterium Moorea bouillonii. Its structure was elucidated by the spectral analysis and the modified Marfey's method. Compound 1 induced differentiation of neural stem cells into astrocytes at the concentration of 10 µM.

    DOI PubMed

    Scopus

    12
    被引用数
    (Scopus)
  • Correction to: Halistanol sulfates I and J, new SIRT1-3 inhibitory steroid sulfates from a marine sponge of the genus Halichondria.

    Fumiaki Nakamura, Norio Kudo, Yuki Tomachi, Akiko Nakata, Misao Takemoto, Akihiro Ito, Hodaka Tabei, Daisuke Arai, Nicole de Voogd, Minoru Yoshida, Yoichi Nakao, Nobuhiro Fusetani

    The Journal of antibiotics   71 ( 4 ) 483 - 483  2018年03月  [国際誌]

     概要を見る

    The original article can be found online at https://doi.org/10.1038/ja.2017.145 .

    DOI PubMed

  • Halistanol sulfates I and J, new SIRT1-3 inhibitory steroid sulfates from a marine sponge of the genus Halichondria.

    Fumiaki Nakamura, Norio Kudo, Yuki Tomachi, Akiko Nakata, Misao Takemoto, Akihiro Ito, Hodaka Tabei, Daisuke Arai, Nicole de Voogd, Minoru Yoshida, Yoichi Nakao, Nobuhiro Fusetani

    The Journal of antibiotics   71 ( 2 ) 273 - 278  2018年02月  [国際誌]

     概要を見る

    Two new analogs of halistanol sulfate (1) were isolated from a marine sponge Halichondria sp. collected at Hachijo-jima Island. Structures of these new halistanol sulfates I (2) and J (3) were elucidated by spectral analyses. Compounds 1-3 showed inhibitory activity against SIRT 1-3 with IC50 ranges of 45.9-67.9, 18.9-21.1 and 21.8-37.5 μM, respectively. X-ray crystallography of the halistanol sulfate (1) and SIRT3 complex clearly indicates that 1 binds to the exosite of SIRT3 that we have discovered in this study.

    DOI PubMed

    Scopus

    18
    被引用数
    (Scopus)

▼全件表示

共同研究・競争的資金等の研究課題

  • 深海性生物混合物を探索源とした新規海洋天然化合物の探索と化合物ライブラリー化

    日本学術振興会  科学研究費助成事業 研究活動スタート支援

    研究期間:

    2021年08月
    -
    2023年03月
     

    中村 文彬

  • 味噌に含まれる抗ストレス活性成分フェルラ酸エチルエステルの作用メカニズム解析

    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:

    2019年04月
    -
    2021年03月
     

    中村 文彬

     概要を見る

    味噌からエピゲノムを指標とした生理活性成分の探索により、抗ストレス活性成分フェルラ酸エチルエステル(FAEE)を明らかにしたが、本成分の作用メカニズムは知られていない。低分子化合物の作用メカニズム解明へのアプローチは様々あるが、エピゲノム調節は酵素だけでなく、様々な補酵素や補因子など数多くの制御因子によって巧妙に制御されているため、FAEEによる直接の標的分子を同定することはメカニズムを理解する上で重要となる。そこで本研究では、FAEEの標的分子および標的遺伝子領域を明らかにすることでFAEEの作用メカニズムの解明を目指している。
    本年度はマウスES細胞から分化誘導した神経幹細胞からのFAEE標的分子候補の探索を行った。令和一年度に合成したFAEEのプローブ分子を用いて、標的分子のプルダウン実験を行った結果、FAEE結合ビーズに特異的なバンドが複数得られた。バンドについてはLC-MS/MSによるアミノ酸配列解析によって候補タンパク質を明らかにしており、現在、その標的分子候補をターゲットとしたshRNAベクターを作製およびノックダウン細胞におけるフェノタイプを確認している。
    また、FAEEの神経分化誘導作用機構を遺伝子発現変化の面から推察するため、FAEEで処理した神経幹細胞からcDNAの調製を行い、RNA-seqを用いた網羅的遺伝子発現解析を行った。FAEE処理によりcontrolと比べて転写量が1.5倍以上に上昇もしくは低下したタンパク質をコードしている遺伝子がそれぞれ24ずつ得られた。また、転写量が2倍以上に変化した114のノンコーディングRNAを得た。これらの遺伝子について、real-time PCRによる遺伝子発現量の確認を行うとともに、神経分化誘導作用との関係性を検証している。

 

特定課題制度(学内資金)

  • 天然化合物の活性評価を目的とした組換えタンパク質の作製

    2022年  

     概要を見る

     これまでセルベースアッセイをもとに、生物活性天然化合物の探索を行ってきたが、同定された活性化合物の多くはその作用機序まで明らかにできていない。化合物が細胞内のどのような標的に作用しているかを同定するのは未だ困難である。一方、様々なタンパク質の新たな機能が年々報告されていることから、これまでセルベースアッセイで見出してきた天然化合物の作用機序の同定を目指して、セルベースアッセイに関連するタンパク質と生物活性化合物との相互作用を確認することを目的に組換えタンパク質作製に取り組んだ。

  • Coronalin Dによる神経分化調節作用のメカニズム解析

    2021年   中尾洋一

     概要を見る

      われわれはin vitro神経分化モデルにて神経幹細胞からアストロサイトへの分化促進活性を有するcoronarin D(coroD)に着目して研究を行っており、本研究では生体内でcoroDが直接結合する標的分子を探索するため、coroDを模倣したプローブ合成を行った。  春ウコン(キョウオウ、C. aromatica)からcoroDの精製(約50 mg)を行い、このcoroDを基質として活性部位を保持したプローブ分子の合成を複数条件で試みたが、所望のプローブ分子は得られなかった。そこで現在、市販標品を出発原料としてcoroDおよびプローブ分子の合成を進めている。