What are the differences between statin and the shortage of cellular cholesterol content in the pathology of rhabdomyolysis ?

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659440
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: University of Tsukuba
• Principal Investigator: NAKAGAWA Yoshimi 筑波大学, 医学医療系, 講師 (80361351)
• Co-Investigator(Kenkyū-buntansha): MATSUZAKA Takashi 筑波大学, 医学医療系, 准教授 (70400679)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: コレステロール代謝 / 骨格筋

Research Abstract

Statin is an inhibitor for HMGCR, which is a rate-limiting enzyme for cholesterol synthesis. Although statin is an effective drug for hypercholesterolemia, statin develops rhabdomyolysis as a side effect. To understand the mechanism of the pathogenesis of rhabdomyolysis by statin, we generated the skeletal muscle-specific HMGCR knockout mice. These mice showed the same phenotypes as rhabdomyolysis. We found that the removal of the insufficient mitochondria by autophagy was dysregulated in skeletal muscle of these mice. Next, we will determine the mechanism that mitochondria function and autophagy are dysfunctioned in skeletal muscle of HMGCR knockout mice.

Research Products

• [Journal Article] TFE3 inhibits myoblast differentiation in C2C12 cells via down-regulating gene expression of myogenin (2013)
  • Author(s): Naka A, Iida KT, Nakagawa Y, Iwasaki H, Takeuchi Y, Satoh A, Matsuzaka T, Ishii KA, Kobayashi K, Yatoh S, Shimada M, Yahagi N, Suzuki H, Sone H, Yamada N, Shimano H.
  • Journal Title: Biochem Biophys Res Commun Volume: 430(2) Pages: 664-9
  • DOI: 10.1016/j.bbrc.2012.11.094
  • Peer Reviewed
• [Remarks] 筑波大学 医学医療系 内分泌代謝・糖尿病 内科
  • URL: http://www.u-tsukuba-endocrinology.jp/