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The strategy to avoid drug-induced skeletal muscle injury involved in monocarboxylate transporter

Research Project

Project/Area Number 24790138
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionHokkaido University

Principal Investigator

KOBAYASHI Masaki  北海道大学, 薬学研究科(研究院), 助教 (70431319)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords薬剤性筋障害 / 乳酸トランスポーター
Research Abstract

Although exercise and drug therapy is important to prevent progress of an arteriosclerotic disease, exercise performance leads to increase drug-induced muscle injury. So the elucidation of this mechanism is needed for avoiding muscular disorder. Since exercise performance induced the expression of monocarboxylate transporter (MCT) 4, we focused on the association between MCT4 and HMG-CoA reductase inhibitors such as statins-induced muscle injury. Atorvastatin, one of statins reduced the number of viable cells and caused dramatic morphological changes and caspase-3/7 activation, and induced MCT4 expression levels in RD cell line as a model of in vitro skeletal muscle. Two siRNAs (10 nM) for MCT4 significantly decreased MCT4 expression at 72 h after transfected to RD cells. Atorvastatin-induced RD cell injury was blocked by MCT4 siRNAs transfected to RD cells. These results suggest that the mechanism of statin-induced muscle injury was associated with MCT4 expression.

Report

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

    (7 results)

All 2013 2012

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (4 results)

  • [Journal Article] Crucial residue involved in L-lactate recognition by human monocarboxylate transporter 4 (hMCT4)2013

    • Author(s)
      Sasaki S, Kobayashi M, Futagi Y, Ogura J, Yamaguchi H, Takahashi N, Iseki K
    • Journal Title

      PLoS ONE.

      Volume: 8 Issue: 7 Pages: 67690-67690

    • DOI

      10.1371/journal.pone.0067690

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the Expression and Activity of Glucose and Lactic Acid Metabolism-Related Genes by Protein Kinase C in Skeletal Muscle Cells2013

    • Author(s)
      Otake S, Kobayashi M, Narumi K, Sasaki S, Kikutani Y, Furugen A, Watanabe M, Takahashi N, Ogura J, Yamaguchi H, Iseki K
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 36 Issue: 9 Pages: 1435-1439

    • DOI

      10.1248/bpb.b13-00141

    • NAID

      130003361512

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Acidification and Alkalinization Agent on Statins-induced Muscle Toxicity2012

    • Author(s)
      Kobayashi M, Hidaka K, Chisaki I, Takahashi N, Ogura J, Itagaki S, Hirano T, Yamaguchi H, Iseki K
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 132 Issue: 5 Pages: 609-615

    • DOI

      10.1248/yakushi.132.609

    • NAID

      130001888677

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2012-05-01
    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] モノカルボン酸輸送担体hMCT4の発現調節機構2013

    • Author(s)
      小林正紀、鳴海克哉、大竹翔、佐々木将太郎、井関健
    • Organizer
      第8回トランスポーター研究会
    • Place of Presentation
      熊本
    • Related Report
      2013 Final Research Report
  • [Presentation] モノカルボン酸輸送担体 hMCT4 の発現調節機構2013

    • Author(s)
      小林正紀, 鳴海克哉, 大竹翔, 佐々木将太郎, 井関健
    • Organizer
      第8回トランスポーター研究会
    • Place of Presentation
      熊本大学薬学部、熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] Regulation of human monocarboxylate transporter 4 in skeletal muscle cells : the role of AMPactivated protein kinase and protein kinase C2012

    • Author(s)
      Kobayashi M, Narumi K, Furugen A, Sasaki S, Iseki K
    • Organizer
      AAPS Annual Meeting and Exposition
    • Place of Presentation
      Chicago
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulation of human monocarboxylate transporter 4 in skeletal muscle cells: the role of AMP-activated protein kinase and protein kinase C2012

    • Author(s)
      Kobayashi M, Narumi K, Furugen A, Sasaki S, Iseki K
    • Organizer
      AAPS Annual Meeting and Exposition
    • Place of Presentation
      McCormic Place, Chicago, USA
    • Related Report
      2012 Research-status Report

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

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