HMG-CoA reductase inhibitor-induced L6 myoblast cell death: Involvement of the phosphatidylinositol 3-kinase pathway

Hiroto Nakagawa, Tatsuro Mutoh, Takanori Kumano, Masaru Kuriyama

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Our previous studies have shown that the HMG-CoA reductase inhibitor (HCRI) causes rhabdomyolysis and electrical myotonia in rabbits and also kills L6 myoblasts in culture. In the present study, we analyzed the intracellular signal transduction pathway of HCRI-induced cell death using L6 myoblasts as a model system. Here, we report that simvastatin, a lipophilic HCRI, efficiently inhibited isoprenylation of Ras proteins and therefore induced translocation of a significant part of Ras proteins from the membrane fraction into the cytosolic fraction within 10 min. With this translocation, PI 3-kinase activity of the Ras-bound form both in total and in the membrane fraction was also decreased profoundly. Furthermore, various PI 3-kinase inhibitors also caused cell death with morphological changes similar to those caused by simvastatin. These results might represent the molecular events of HCRI-induced cell death, and suggest the significance of PI 3-kinase activity of the Ras-bound form in the maintenance of cell viability. Copyright (C) 1998 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)289-292
Number of pages4
JournalFEBS Letters
Volume438
Issue number3
DOIs
Publication statusPublished - 06-11-1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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