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  • 标题:Fibrates and Statins Rapidly and Synergistically Induce Pyruvate Dehydrogenase Kinase 4 mRNA in the Liver and Muscles of Mice
  • 本地全文:下载
  • 作者:Kiyoto Motojima ; Kouichi Seto
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2003
  • 卷号:26
  • 期号:7
  • 页码:954-958
  • DOI:10.1248/bpb.26.954
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:We previously identified pyruvate dehydrogenase kinase 4 (PDK4) mRNA as a most rapidly induced mRNA by fibrates and suggested the possibility that the coupled induction of PDK4 and reduction of serum triglyceride and fatty acid levels can cause protein degradation in muscles. To investigate whether the drugs that are known to have a risk of rhabdomyolysis induce PDK4 mRNA in skeletal muscle, the effects of statins and new quinolon anti-bacterial drugs on the expression levels of the mRNA were examined using mice and cultured cells. Several statins and new quinolon anti-bacterial drugs solely induced PDK4 mRNA in the muscle as efficiently as fibrates and at least some combinations were synergistic. The present results suggest that induction of PDK4 mRNA is involved in the drug induced acute rhabdomyolysis when the muscle is restricted to use fatty acids as a major energy source.
  • 关键词:peroxisome proliferator-activated receptor (PPAR);hypolipidemic effect;fibrate;pyruvate dehydrogenase kinase 4 (PDK4);metabolic switching;rhabdomyolysis
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