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

• Project/Area Number: 24790138
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Hokkaido 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: ¥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.

Research Products

• [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
  • 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 Cells (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Effects of Acidification and Alkalinization Agent on Statins-induced Muscle Toxicity (2012)
  • 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
  • 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
• [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
• [Presentation] Regulation of human monocarboxylate transporter 4 in skeletal muscle cells : the role of AMPactivated protein kinase and protein kinase C (2012)
  • Author(s): Kobayashi M, Narumi K, Furugen A, Sasaki S, Iseki K
  • Organizer: AAPS Annual Meeting and Exposition
  • Place of Presentation: Chicago
• [Presentation] Regulation of human monocarboxylate transporter 4 in skeletal muscle cells: the role of AMP-activated protein kinase and protein kinase C (2012)
  • 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