Role of tyrosine phosphorylation of phospholipase C γ1 in the signaling pathway of HMG‐CoA reductase inhibitor‐induced cell death of L6 myoblasts

FEBS Letters

Kuriyama, Masaru¹  Mutoh, Tatsuro¹  Kumano, Takanori¹  Nakagawa, Hiroto¹ 

[1] The 2nd Department of Internal Medicine, Division of Neurology, Faculty of Medicine, Fukui Medical University, 23-Shimoaizuki, Matsuoka-cho, Fukui 910-11, Japan

关键词: HMG-coenzyme A reductase inhibitor;    Tyrosine phosphorylation;    Phospholipase C γ1;    Apoptosis;    L6 myoblast;   

DOI  :  10.1016/S0014-5793(99)00188-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Our previous studies have shown that the HMG-CoA reductase (HCR) inhibitor (HCRI), simvastatin, kills L6 myoblasts by involving Ca²⁺ mobilization from the Ca²⁺ pool in the cells but not by influx from extracellular space. More recently, we found that HCRI induced tyrosine phosphorylation of several cellular proteins, followed by apoptotic cell death of L6 myoblasts. The present study was aimed to elucidate the molecular target(s) of these tyrosine phosphorylations induced by HCRI and demonstrated that simvastatin induces tyrosine phosphorylation of phospholipase C (PLC) γ1. This tyrosine phosphorylation of PLC-γ1 caused the increment of the intracellular inositol triphosphate (IP3) levels in L6 myoblasts. Pretreatment of the cells with herbimycin A, a specific inhibitor of protein tyrosine kinase, inhibited a simvastatin-induced increase in IP3 level in the cells as well as tyrosine phosphorylation of PLC-γ1. Interestingly, pretreatment of the cells with U-73122, a specific inhibitor of PLC, prevented simvastatin-induced cell death. Thus, these results strongly suggest that simvastatin-induced tyrosine phosphorylation of PLC-γ1 plays, at least in part, an important role for the development of simvastatin-induced cell death.

【 授权许可】

Unknown