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Identify the novel target molecules of valproic acid using model organism

Research Project

Project/Area Number 26460339
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionKobe University

Principal Investigator

Yan Ma  神戸大学, 医学部附属病院, 医員 (70457050)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsバルプロ酸 / 分子標的 / 分裂酵母 / TORC1経路 / 酵母モデル生物 / 遺伝子発現 / 薬物感受性
Outline of Final Research Achievements

Valproic acid (VPA) is widely used as an anticonvulsant drug. More recently, it has been reported that VPA improved the efficiency upon iPS reprogramming and the administration of VPA dramatically enhanced the restoration of hind limb function. The exact target molecules of the various effects of VPA remain unclear. We have developed a genetic approach using S pombe as a model organism. This study led to the following findings. We identified a novel VPA sensitive mutant of vas4-1/vrg4-v4, a mutant allele of the vrg4+ gene encoding S pombe homolog of Golgi GDP-mannose transmembrane transporter, and its mammalian homologue encodes disease responsible gene of cochlear like pelvic dysplasia. We found that Vrg4 localizes to Golgi, and isolated several genes as dosage-dependent suppressors of the VPA-sensitive phenotype of vrg4-v4 mutant. Furthermore we found the expression level of many genes was markedly increased or decreased upon VPA treatment using cap analysis of gene expression.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (10 results)

All 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 4 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] China Medical University(中国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] The loss of Lam2 and Npr2-Npr3 diminishes the vacuolar localization of Gtr1-Gtr2 and disinhibits TORC1 activity in fission yeast.2016

    • Author(s)
      Ma N, Ma Y, Nakashima A, Kikkawa U, Furuyashiki T.
    • Journal Title

      PLoS One

      Volume: 11 Issue: 5 Pages: e0156239-e0156239

    • DOI

      10.1371/journal.pone.0156239

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic Interactions among AMPK Catalytic Subunit Ssp2 and Glycogen Synthase Kinases Gsk3 and Gsk31 in Schizosaccharomyces Pombe2016

    • Author(s)
      QingYun, Yan Ma, Toshiaki Kato,Tomoyuki Furuyashiki
    • Journal Title

      Kobe J. Med. Sci.

      Volume: 62

    • NAID

      120005866883

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Constitutive Tor2 Activity Promotes Retention of the Amino Acid Transporter Agp3 at Trans-Golgi/Endosomes in Fission Yeast2015

    • Author(s)
      Qingbin Liu, Yan Ma, Xin Zhou, Tomoyuki Furuyashiki
    • Journal Title

      PLoS One

      Volume: 10 Issue: 10 Pages: e0139045-e0139045

    • DOI

      10.1371/journal.pone.0139045

    • NAID

      120005670614

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Azoles activate Atf1-mediated transcription through MAP kinase pathway for antifungal effects in fission yeast2015

    • Author(s)
      Lingling Hu, Tsutomu Hayafuji, Yue Fang, Yan Ma, Tomoyuki Furuyashiki
    • Journal Title

      Genes Cells

      Volume: 20 Issue: 9 Pages: 695-705

    • DOI

      10.1111/gtc.12263

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Characterization of Tamoxifen as an Antifungal Agent Using the Yeast Schizosaccharomyces Pombe Model Organism2015

    • Author(s)
      Xibo Zhang , Yue Fang, Wurentuya Jaiseng , Lingling Hu , Yabin Lu , Yan Ma, Tomoyuki Furuyashiki
    • Journal Title

      Kobe J Med Sci. 2015 Oct 9;61(2):

      Volume: 61

    • NAID

      120005661465

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Tor Signaling Regulates Transcription of Amino Acid Permeases through a GATA Transcription Factor Gaf1 in Fission Yeast. Ma Y, Ma N, Liu Q, Qi Y, Manabe R, Furuyashiki T.2015

    • Author(s)
      Yan Ma, Ning Ma, Qingbin Liu, Yao Qi, Ri-ichiroh Manabe, Tomoyuki Furuyashiki
    • Journal Title

      PLoS One

      Volume: 10 Issue: 12 Pages: e0144677-e0144677

    • DOI

      10.1371/journal.pone.0144677

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The MluI cell cycle box (MCB) motifs, but not damage-responsive elements (DREs), are responsible for the transcriptional induction of the rhp51+ gene in response to DNA replication stress.2014

    • Author(s)
      Sartagul W, Zhou X, Yamada Y, Ma N, Tanaka K, Furuyashiki T, Ma Y.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 11 Pages: e111936-e111936

    • DOI

      10.1371/journal.pone.0111936

    • NAID

      120005549610

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Tor2 activity promotes retention of Agp3 amino acid transporter in trans-Golgi/endosomes in fission yeast2015

    • Author(s)
      Yan Ma, Qingbin Liu, Ning Ma, Yao Qi, Xin Zhou, Tomoyuki Furuyashiki
    • Organizer
      pombe 2015, 8th International Fission Yeast Meeting
    • Place of Presentation
      Kobe
    • Year and Date
      2015-06-21
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 分裂酵母においてTORはGATA転写因子を介してアミノ酸輸送体Isp5の転写を制御する2015

    • Author(s)
      馬 艶、馬 寧、劉 慶彬、斉 瑤、古屋敷 智之
    • Organizer
      第88回 日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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