ERK and p38 MAPK are involved in the antiapoptotic action of 17β-Estradiol in skeletal muscle cells

RONDA CAROLINA,; VASCONSUELO, ANDREA ANAHÍ; BOLAND RICARDO,

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Año: 2010 vol. 206 p. 235 - 246

0022-0795

17beta-estradiol stimulates the mitogen activated protein kinases (MAPKs) in various cellular types. We have shown that the hormone activates Extracellular Regulated Kinase (ERK) and p38 MAPK in skeletal muscle cells. However, the functions of MAPK modulation by the estrogen in muscle cells have not been studied yet. We recently reported antiapoptotic actions of 17beta-estradiol in C2C12 cells. Here, the role of MAPKs mediating the hormone effect in muscle cells was investigated. The results showed that cells exposed to 0.5 mM H(2)O(2) presented cytoskeleton disorganization, mitochondria redistribution and picnotic/fragmented nuclei. Pretreatment with 10(-8) M 17beta-estradiol prevented these morphological apoptotic characteristics, except in presence of ERK or p38 MAPK inhibitors, U0126 and SB203580, respectively. Mitochondrial membrane integrity was also studied. Preincubation of cultures with 10(-8) M 17beta-estradiol abrogated H(2)O(2) effects such as Janus Green oxidation, presence of cytochrome c oxidase activity in the cytoplasm and Smac/Diablo release from mitochondria. When MAPKs were inhibited, the hormone could not prevent mitochondrial membrane damage exerted by the oxidative stress. Blocking experiments with siRNAs confirmed that both ERK and p38 MAPK mediate the antiapoptotic effects of the hormone at the mitochondria level. Moreover, some of the molecular mechanisms involved were investigated. Thus, 17beta-estradiol was able to induce Akt (Ser473) and Bad (Ser112) phosphorylation in C2C12 cells in absence or presence of H(2)O(2) but not when the cultures were incubated with H(2)O(2) and MAPKs inhibitors. Altogether, these results show that 17beta-estradiol exerts a survival action in skeletal muscle cells involving ERK and p38 MAPK activation.