17b-Estradiol protects mitochondrial functions through extracellular-signal-regulated kinase in C2C12 muscle cells

RONDA ANA CAROLINA; VASCONSUELO ANDREA; BOLAND RICARDO

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY : INTERNATIONAL JOURNAL OF EXPERIMENTAL CELLULAR PHYSIOLOGY, BIOCHEMISTRY, AND PHARMACOLOGY.

KARGER

Lugar: Basel; Año: 2013 vol. 32 p. 1011 - 1023

1015-8987

We have previously shown that exposure to 17beta-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, using the murine skeletal muscle cell line C2C12 as experimental model, we focused on the effects of the estrogen on mitochondria. Immunocytochemistry and Western blot assays showed that E2 activates ERK and then induces its translocation to mitochondria. Using the pharmacological inhibitor of ERK activation, U0126, we evaluated the role of the MAPK in E2 regulation of cytochrome c oxidase complex IV (COXIV) activity. The results showed that E2, through ERK activation, is able to enhance COXIV activity. Moreover, it was shown by coimmunoprecipitation assays that 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. Using the JC-1 dye to evaluate mitochondrial membrane potential we observed that the estrogen inhibits the collapse of mitochondrial membrane potential induced by H2O2, involving ERK and COXIV. 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.