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Molecular mechanism of autophagic abnormality in mouse model with rhabdomyolysis

Research Project

Project/Area Number 15K15344
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Metabolomics
Research InstitutionUniversity of Tsukuba

Principal Investigator

SHIMANO Hitoshi  筑波大学, 医学医療系, 教授 (20251241)

Co-Investigator(Kenkyū-buntansha) 中川 嘉  筑波大学, 国際統合睡眠医科学研究機構, 准教授 (80361351)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsスタチン / 横紋筋融解症 / オートファジー / コレステロール / コレステロール合成系 / HMGCR / コレステロール合成
Outline of Final Research Achievements

This study was aimed to elucidate the mechanism of the onset of rhabdomyolysis, which is a side effect of statin which is a treatment for hypercholesterolemia. We generated skeletal muscle specific-HMGCR, a target of statin, knockout mice. The turnover between cell death and regeneration were frequently occurred in muscle cells of mKO mice, indicating that the deficiency of HMGCR in skeletal muscle leads to myopathy. We examined the relationship between myopathy and autophagy in skeletal muscle of these mice. The function of Rab7, which is involved in the formation of autolysosomes, was impaired and the degradation of autolysosomes was he also impaired in skeletal muscle of these mice. Thus, we found that the skeletal muscle cells of mKO mice exhibited the abnormality of autolysosomes and the increase of p62 protein, due to the functional abnormality of lysosome.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (2 results)

All 2015 Other

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Remarks (1 results)

  • [Journal Article] Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy.2015

    • Author(s)
      Osaki Y, Nakagawa Y, Miyahara S, Iwasaki H, Ishii A, Matsuzaka T, Kobayashi K, Yatoh S, Takahashi A, Yahagi N, Suzuki H, Sone H, Ohashi K, Ishibashi S, Yamada N, Shimano H
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 466(3) Issue: 3 Pages: 536-540

    • DOI

      10.1016/j.bbrc.2015.09.065

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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/

    • Related Report
      2016 Annual Research Report 2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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