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Elucidation of the molecular mechanism by which valproic acid affects intracellular membrane traffic

Research Project

Project/Area Number 24790251
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionKobe University

Principal Investigator

MA YAN  神戸大学, 医学(系)研究科(研究院), 講師 (70457050)

Co-Investigator(Renkei-kenkyūsha) KUNO Takayoshi  神戸大学, 大学院医学研究科, 教授 (50144564)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsバルプロ酸 / メンブレン・トラフィック / モデル生物 / 薬物感受性 / 細胞膜輸送 / 薬物副作用 / 薬物相互作用
Research Abstract

Valproic acid (VPA) is widely used as an anticonvulsant drug. More recently, it has been reported that VPA improved the efficiency by more than 100-fold upon iPS reprogramming and the administration of VPA dramatically enhanced the restoration of hind limb function upon transplantation of neural stem cells. The exact mechanisms of action of VPA in these conditions remain unclear, although it has been shown to alter a wide variety of signaling pathways. We have been using Schizosaccharomyces pombe as a model organism to study the molecular mechanisms of VPA action. This study led to the following findings. We performed a genome-wide screen of non-essential haploid deletion strains and confirmed 148 deletion strains to be VPA sensitive. Most of the VPA sensitive strains did not show sensitivity to another aliphatic acid sodium butyrate.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (47 results)

All 2013 2012 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (29 results) Remarks (3 results)

  • [Journal Article] Possible Involvement of Nitric Oxide and Reactive Oxygen Species in Glucose Deprivation-Induced Activation of Transcription Factor Rst22013

    • Author(s)
      Toshiaki Kato, Xin Zhou, and Yan Ma
    • Journal Title

      PLoS ONE

      Volume: 8(10)

    • NAID

      120005465545

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] TORC1 Signaling Is Governed by Two Negative Regulators in Fission Yeast2013

    • Author(s)
      Ning Ma, Qingbin Liu, Lili Zhang, Elizabeth Petri Henske, and Yan Ma
    • Journal Title

      Genetics

      Volume: 195(2) Pages: 457-68

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genome-Wide Screening for Genes Associated with Valproic Acid Sensitivity in Fission Yeast2013

    • Author(s)
      Lili Zhang, Ning Ma, Qingbin Liu, and Yan Ma
    • Journal Title

      PLoS ONE

      Volume: 8(7)

    • NAID

      120005468175

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Genome-Wide Screening of Potential Target Genes to Enhance the Antifungal Activity of Micafungin in Schizosaccharomyces pombe2013

    • Author(s)
      Xin Zhou, Yan Ma, Yue Fang, Wugan gerile, Wurentuya Jaiseng, Yuki Yamada, and Takayoshi Kuno
    • Journal Title

      PLoS ONE

      Volume: 8(5)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible Involvement of Nitric Oxide and Reactive Oxygen Species in Glucose Deprivation-Induced Activation of Transcription Factor Rst22013

    • Author(s)
      Toshiaki Kato, Xin Zhou, Yan Ma
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 10 Pages: e78012-e78012

    • DOI

      10.1371/journal.pone.0078012

    • NAID

      120005465545

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TORC1 Signaling Is Governed by Two Negative Regulators in Fission Yeast2013

    • Author(s)
      Ning Ma, Qingbin Liu, Lili Zhang, Elizabeth Petri Henske, Yan Ma
    • Journal Title

      Genetics

      Volume: 195 Issue: 2 Pages: 457-68

    • DOI

      10.1534/genetics.113.154674

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-Wide Screening for Genes Associated with Valproic Acid Sensitivity in Fission Yeast2013

    • Author(s)
      Lili Zhang, Ning Ma, Qingbin Liu, Yan Ma
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 7 Pages: e68738-e68738

    • DOI

      10.1371/journal.pone.0068738

    • NAID

      120005468175

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Genome-Wide Screening of Potential Target Genes to Enhance the Antifungal Activity of Micafungin in Schizosaccharomyces pombe2013

    • Author(s)
      Xin Zhou, Yan Ma, Yue Fang, Wugan gerile, Wurentuya Jaiseng, Yuki Yamada, Takayoshi Kuno
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 5 Pages: e65904-e65904

    • DOI

      10.1371/journal.pone.0065904

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide screen reveals novel mechanisms for regulating cobalt uptake and detoxification in fission yeast2012

    • Author(s)
      Sayomi Ryuko, Yan Ma, Ning Ma, Motoyoshi Sakaue, and Takayoshi Kuno
    • Journal Title

      Mol Genet Genomics

      Volume: 287

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A measurable activation of the bZIP transcription factor Atf1 in a fission yeast strain devoid of stress-activated and cell-integrity MAPK activities2012

    • Author(s)
      Xin Zhou, Yan Ma, Toshiaki Kato, and Takayoshi Kuno
    • Journal Title

      J. Biol. Chem

      Volume: 287(28) Pages: 23434-23439

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Genetic and Pharmacological Analysis of Isoprenoid Pathway by LC-MS/MS in Fission Yeast2012

    • Author(s)
      Tomonori Takami
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 11 Pages: e49004-e49004

    • DOI

      10.1371/journal.pone.0049004

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Studies on the Roles of Clathrin-Mediated Membrane Trafficking and Zinc Transporter Cis4 in the Transport of GPI-Anchored Proteins in Fission Yeast2012

    • Author(s)
      Jaiseng W, Fang Y, Ma Y, Sugiura R, Kuno T
    • Journal Title

      PLoS ONE

      Volume: 7(7) Issue: 7 Pages: 19294-19303

    • DOI

      10.1371/journal.pone.0041946

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genome-wide screen reveals novel mechanisms for regulating cobalt uptake and detoxification in fission yeast2012

    • Author(s)
      Ryuko S, Ma Y, Ma N, Sakaue M, Kuno T
    • Journal Title

      Mol Genet Genomics

      Volume: 287(8):651-62 Issue: 8 Pages: 651-62

    • DOI

      10.1007/s00438-012-0705-9

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A measurable activation of the bZIP transcription factor Atf1 in a fission yeast strain devoid of stress-activated and cell-integrity MAPK activities.2012

    • Author(s)
      Xin Zhou, Yan Ma, Toshiaki Kato, and Takayoshi Kuno
    • Journal Title

      J. Biol. Chem.

      Volume: 287 Issue: 28 Pages: 23434-23439

    • DOI

      10.1074/jbc.c111.338715

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genetic screening for regulators of Prz1, a transcriptional factor acting downstream of calcineurin in fission yeast2012

    • Author(s)
      Atsushi Koike, Toshiaki Kato, Reiko Sugiura, Yan Ma, Yuki Tabata, Koji Ohmoto, Susie O. Sio, Takayoshi Kuno
    • Journal Title

      J. Biol. Chem.

      Volume: 287 Issue: 23 Pages: 19294-19303

    • DOI

      10.1074/jbc.m111.310615

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 低グルコース状態おける転写因子Rst2の活性化に一酸化窒素・活性酸素種が関与する2013

    • Author(s)
      加藤俊明, 周キン, 馬艶
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-03
    • Related Report
      2013 Final Research Report
  • [Presentation] TORC1 signaling is governed by two negative regulators in fission yeast2013

    • Author(s)
      Ma Ning, Liu Qingbin, Zhang Lili, Henske Elizabeth, Yan Ma
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-03
    • Related Report
      2013 Final Research Report
  • [Presentation] アゾール系抗真菌薬に応答する分裂酵母Erg11プロモーターの解析2013

    • Author(s)
      早藤励, 胡玲玲, 房月, 馬艶
    • Organizer
      第124回日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Year and Date
      2013-11-01
    • Related Report
      2013 Final Research Report
  • [Presentation] 分裂酵母モデル系を用いた脊髄性筋萎縮症の原因タンパク質Smn1の機能解明2013

    • Author(s)
      西島数人, 加藤俊明, 馬艶, 西尾久英
    • Organizer
      第124回日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Year and Date
      2013-11-01
    • Related Report
      2013 Final Research Report
  • [Presentation] 分子遺伝学的手法によるTORの関連遺伝子の探索2013

    • Author(s)
      福間久友, 馬寧, 斉瑶, 馬艶
    • Organizer
      第124回日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Year and Date
      2013-11-01
    • Related Report
      2013 Final Research Report
  • [Presentation] Feedback regulation of TORC1 signaling in fission yeast2013

    • Author(s)
      Ning Ma, Qingbin Liu, Lili Zhang, Yao Qi, Yan Ma
    • Organizer
      The 2013 American Society for Cell Biology Annual Meeting
    • Place of Presentation
      New Orleans, LA
    • Related Report
      2013 Final Research Report
  • [Presentation] Possible involvement of nitric oxide and reactive oxygen species in glucose deprivation-induced activation of transcription factor Rst22013

    • Author(s)
      Toshiaki Kato, Xin Zhou, Yan Ma
    • Organizer
      The 2013 American Society for Cell Biology Annual Meeting
    • Place of Presentation
      New Orleans, LA
    • Related Report
      2013 Final Research Report
  • [Presentation] Feedback regulation of TORC1 signaling by Npr2, but not by Tsc22013

    • Author(s)
      Yan Ma, Ning Ma, Qingbin Liu, Lili Zhang, Elizabeth Henske, Takayoshi Kuno
    • Organizer
      EMBO Conference on Fission Yeast : pombe 2013, 7th International Fission Yeast Meeting
    • Place of Presentation
      London, United Kingdom
    • Related Report
      2013 Final Research Report
  • [Presentation] Npr2 Negatively Regulates TORC1 Signaling in Fission Yeast2013

    • Author(s)
      Ning Ma, Qingbin Liu, Lili Zhang, Elizabeth P. Henske, Yan Ma
    • Organizer
      酵母遺伝学フォーラム第46回研究報告会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Genome-Wide Screening for Genes Associated with Valproic Acid Sensitivity in Fission Yeast2013

    • Author(s)
      Lili Zhang, Ning Ma, Qingbin Liu, Yan Ma
    • Organizer
      酵母遺伝学フォーラム第46回研究報告会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] ラパマイシン標的分子Tor2制御におけるNpr2の役割 : ゲノムワイド解析による解明2013

    • Author(s)
      馬艶, 馬寧, 劉慶彬, 張麗麗, 福間久友, 西島数人, 久野高義
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] アゾール系抗真菌薬に応答する分裂酵母Erg11プロモーターの解析2013

    • Author(s)
      早藤 励、胡 玲玲、房 月、馬 艶
    • Organizer
      第124回 日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 分裂酵母モデル系を用いた脊髄性筋萎縮症の原因タンパク質Smn1の機能解明2013

    • Author(s)
      西島 数人、加藤 俊明、馬 艶、西尾 久英
    • Organizer
      第124回 日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 分子遺伝学的手法によるTORの関連遺伝子の探索2013

    • Author(s)
      福間久友、馬 寧、斉 瑶、馬 艶
    • Organizer
      第124回 日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] Feedback regulation of TORC1 signaling in fission yeast2013

    • Author(s)
      Ning Ma, Qingbin Liu, Lili Zhang, Yao Qi, Yan Ma
    • Organizer
      The 2013 American Society for Cell Biology Annual Meeting
    • Place of Presentation
      New Orleans
    • Related Report
      2013 Annual Research Report
  • [Presentation] Possible involvement of nitric oxide and reactive oxygen species in glucose deprivation-induced activation of transcription factor Rst22013

    • Author(s)
      Toshiaki Kato, Xin Zhou, Yan Ma
    • Organizer
      The 2013 American Society for Cell Biology Annual Meeting
    • Place of Presentation
      New Orleans
    • Related Report
      2013 Annual Research Report
  • [Presentation] Feedback regulation of TORC1 signaling by Npr2, but not by Tsc22013

    • Author(s)
      Yan Ma, Ning Ma, Qingbin Liu, Lili Zhang, Elizabeth Henske, Takayoshi Kuno
    • Organizer
      EMBO Conference on Fission Yeast: pombe 2013, 7th International Fission Yeast Meeting
    • Place of Presentation
      London
    • Related Report
      2013 Annual Research Report
  • [Presentation] 低グルコース状態おける転写因子Rst2の活性化に一酸化窒素・活性酸素種が関与する2013

    • Author(s)
      加藤 俊明, 周 キン, 馬 艶
    • Organizer
      第36回 日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] TORC1 signaling is governed by two negative regulators in fission yeast2013

    • Author(s)
      Ning Ma, Qingbin Liu, Lili Zhang, Elizabeth Henske, Yan Ma
    • Organizer
      第36回 日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] ラパマイシン標的分子Tor2制御におけるNpr2の役割:ゲノムワイド解析による解明2013

    • Author(s)
      馬 艶、馬 寧、劉 慶彬、張 麗麗、福間久友、 西島数人、久野高義
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] 分裂酵母におけるNO応答転写調節メカニズムの解明2012

    • Author(s)
      烏干格日楽, 山田優希, 加藤俊明, Xin Zhou, 馬艶, 久野高義
    • Organizer
      第122回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2012-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 分裂酵母におけるDNA損傷応答メカニズムの解明2012

    • Author(s)
      山田優希, 烏干格日楽, Xin Zhou, 馬艶, 久野高義
    • Organizer
      第122回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2012-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 低グルコースで活性化される転写因子Rst2の転写活性のリアルタイムモニタリング2012

    • Author(s)
      加藤俊明, 馬艶, 久野高義
    • Organizer
      第122回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2012-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 分裂酵母ノックアウトライブラリーを用いたバルプロ酸感受性遺伝子の探索と解析2012

    • Author(s)
      張麗麗, 馬艶, 馬寧, 劉慶彬, 久野高義
    • Organizer
      第122回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2012-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 分裂酵母ノックアウトライブラリーを用いた亜鉛感受性及び耐性遺伝子のゲノムワイドスクリーニング2012

    • Author(s)
      長谷川よしの, 柳幸佐代美, 馬艶, 久野高義
    • Organizer
      第122回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2012-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 分裂酵母におけるNO応答転写調節メカニズムの解明2012

    • Author(s)
      烏干格日楽、山田優希、加藤俊明、Xin Zhou、馬 艶、久野高義
    • Organizer
      第122回 日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] 分裂酵母におけるDNA 損傷応答メカニズムの解明2012

    • Author(s)
      山田優希、烏干格日楽、Xin Zhou、馬 艶、久野高義
    • Organizer
      第122回 日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] 分裂酵母ノックアウトライブラリーを用いたバルプロ酸感受性遺伝子の探索と解析2012

    • Author(s)
      張 麗麗、馬 艶、馬 寧、劉 慶彬、久野高義
    • Organizer
      第122回 日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] 分裂酵母ノックアウトライブラリーを用いた亜鉛感受性及び耐性遺伝子のゲノムワイドスクリーニング2012

    • Author(s)
      長谷川よしの、柳幸佐代美、馬 艶、久野高義
    • Organizer
      第122回 日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.med.kobe-u.ac.jp/pharma/welcome.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 分子薬理・薬理ゲノム学研究室 業績

    • URL

      http://www.med.kobe-u.ac.jp/pharma/histor.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 分子薬理・薬理ゲノム学分野ホームページ

    • URL

      http://www.med.kobe-u.ac.jp/pharma/histor.html

    • Related Report
      2012 Research-status Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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