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

避免涉及单羧酸转运蛋白的药物引起的骨骼肌损伤的策略

• 批准号: 24790138
• 负责人: KOBAYASHI Masaki
• 金额: $ 2.91万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790138/
• 关键词: 薬剤性筋障害; 乳酸トランスポーター

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.

虽然运动和药物治疗对预防动脉硬化疾病的进展很重要，但运动表现会增加药物性肌肉损伤。因此，阐明这一机制是避免肌肉疾病的必要条件。由于运动表现诱导了单羧酸转运蛋白（MCT） 4的表达，我们重点研究了MCT4与HMG-CoA还原酶抑制剂（如他汀类药物诱导的肌肉损伤）之间的关系。他汀类药物之一阿托伐他汀在体外骨骼肌模型RD细胞系中降低活细胞数量，引起显著的形态学改变和caspase-3/7激活，并诱导MCT4表达水平。转染到RD细胞72 h后，MCT4的两个sirna （10 nM）显著降低了MCT4的表达。转染到RD细胞的MCT4 sirna可阻断阿托伐他汀诱导的RD细胞损伤。这些结果表明，他汀类药物诱导的肌肉损伤机制与MCT4的表达有关。

项目成果

モノカルボン酸輸送担体hMCT4の発現調節機構

单羧酸转运蛋白hMCT4的表达调控机制

• 发表时间: 2013
• 作者: 小林正紀;鳴海克哉;大竹翔;佐々木将太郎;井関健
• 通讯作者: 井関健

Regulation of human monocarboxylate transporter 4 in skeletal muscle cells: the role of AMP-activated protein kinase and protein kinase C

骨骼肌细胞中人单羧酸转运蛋白 4 的调节：AMP 激活蛋白激酶和蛋白激酶 C 的作用

• 发表时间: 2012
• 作者: Kobayashi M;Narumi K;Furugen A;Sasaki S;Iseki K
• 通讯作者: Iseki K

Regulation of the Expression and Activity of Glucose and Lactic Acid Metabolism-Related Genes by Protein Kinase C in Skeletal Muscle Cells

蛋白激酶C对骨骼肌细胞中葡萄糖和乳酸代谢相关基因表达和活性的调节

• DOI: 10.1248/bpb.b13-00141
• 发表时间: 2013
• 期刊: Biological and Pharmaceutical Bulletin
• 影响因子: 2
• 作者: Otake S;Kobayashi M; Narumi K;Sasaki S;Kikutani Y;Furugen A;Watanabe M;Takahashi N;Ogura J;Yamaguchi H;Iseki K
• 通讯作者: Iseki K

Regulation of human monocarboxylate transporter 4 in skeletal muscle cells : the role of AMPactivated protein kinase and protein kinase C

骨骼肌细胞中人单羧酸转运蛋白4的调节：AMP激活蛋白激酶和蛋白激酶C的作用

• 发表时间: 2012
• 作者: Kobayashi M;Narumi K;Furugen A;Sasaki S;Iseki K
• 通讯作者: Iseki K

Effects of Acidification and Alkalinization Agent on Statins-induced Muscle Toxicity

酸化碱化剂对他汀类药物引起的肌肉毒性的影响

• DOI: 10.1248/yakushi.132.609
• 发表时间: 2012
• 期刊: YAKUGAKU ZASSHI
• 影响因子: 0.3
• 作者: Kobayashi M;Hidaka K;Chisaki I;Takahashi N;Ogura J;Itagaki S;Hirano T;Yamaguchi H;Iseki K
• 通讯作者: Iseki K