Statin-Induced Myopathy Is Associated with Mitochondrial Complex III Inhibition
作者： Tom J.J. Schirris , G. Herma Renkema , Tina Ritschel , Nicol C. Voermans , Albert Bilos
DOI: 10.1016/J.CMET.2015.08.002
关键词:
摘要: Cholesterol-lowering statins effectively reduce the risk of major cardiovascular events. Myopathy is most important adverse effect, but its underlying mechanism remains enigmatic. In C2C12 myoblasts, several statin lactones reduced respiratory capacity and appeared to be strong inhibitors mitochondrial complex III (CIII) activity, up 84% inhibition. The were in general three times more potent inducers cytotoxicity than their corresponding acid forms. Qo binding site CIII was identified as off-target lactones. These findings could confirmed muscle tissue patients suffering from statin-induced myopathies, which enzyme activity by 18%. Respiratory inhibition myoblasts attenuated convergent electron flow into CIII, restoring respiration 89% control. conclusion, a potential associated with myopathies.
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