17β-Estradiol Protects Mitochondrial Functions through Extracellular-Signal-Regulated Kinase in C2C12 Muscle Cells

Cellular Physiology and Biochemistry

关键词: Apoptosis;    Muscle;    17β-estradiol;    ERK;    COXIV;    Mitochondrial membrane potential;   

DOI  :  10.1159/000354502

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims We have previously shown that exposure to 17β-estradiol (E2) prior to induction of apoptosis with H₂O₂ protects skeletal muscle cells against oxidative damage. However, the mechanism involved in the protective action of the hormone is poorly understood. In the present study, we focused on the mechanism by which ERK mediates this survival effect in connection with COXIV activity and mitochondrial membrane potential. Methods Immunocytochemistry, Western blot, cytochrome c oxidase complex IV (COXIV) activity, coimmunoprecipitation and JC-1 dye by flow cytometry were carried out using C2C12 myoblasts as experimental model. Results E2 is able to activate ERK and then induces its translocation to mitochondria. Using the pharmacological inhibitor of ERK activation U0126 we show that E2, through ERK activation, is able to enhance COXIV activity. Moreover, the hormone increases the interaction between COXIV and ERK. Also, we found that hydrogen peroxide decreases COXIV activity and that preincubation of the cells with E2 prior to induction of apoptosis prevents this effect. In addition, we observe that the estrogen inhibits the collapse of mitochondrial membrane potential induced by H₂O₂, involving ERK and COXIV. Conclusion Our data demonstrate that E2 promotes ERK activation and translocation to mitochondria preventing the decline in COXIV activity and in turn, alteration of mitochondrial membrane potential by oxidative stress, in C2C12 myoblasts.

【 授权许可】

CC BY-NC-ND