17beta-estradiol as pro-survival agent: HSP27 a new target in the regulation of apoptosis in muscle cells?

VASCONSUELO, ANDREA; RONDA, ANA C; MILANESI, LORENA; BOLAND, RICARDO

BONE

ELSEVIER SCIENCE INC

Año: 2008 vol. 43 p. 133 - 133

8756-3282

We previously demonstrated that the steroid hormone 17b-estradiol abrogates apoptosis through estrogen receptors a and b, PI3K/Akt and the ERK 1/2 pathway in C2C12 murine skeletal muscle cells. Here we show that HSP27 is a mediator in the molecular mechanism that transduces the survival signal of the estrogen.  Initially, we observed that 17b-estradiol at physiological concentrations increases the expression of the chaperone after 40 min of treatment. To examine whether this effect plays any role in the antiapoptotic action of the hormone we used quercetin, an inhibitor of HSPs, and found that under this condition 17b-estradiol was  ineffective to block apoptosis. Western blot analysis performed using an anti-caspase-3 antibody showed that the estrogen prevented, through the ERK1/2 pathway, activation of caspase-3 induced by H2O2. In presence of quercetin, this inhibition by the steroid is not observed. By coimmunoprecipation and immunocytochemistry assays with confocal microscopy we found that the chaperone is able to interact with ER b at mitochondria and in presence of 17b-estradiol, with caspase-3. The interaction with caspase-3 was not evidenced in apoptotic cells. These findings could be of importance in myopathies associated to disregulation of apoptosis, which could be overcome depleting or overexpressing HSP27.