El 17beta-estradiol ejerce efectos protectivos en celulas musculares esqueleticas a nivel de la via apoptotica de la MAPKKK, ASK1.

NOELIA ZANETTI; LORENA MILANESI; RICARDO BOLAND

Universidad Nacional del Sur. Bahia Blanca, Argentina

Jornada; Jornadas de Postgrado del Departamento de Biologia, Bioquimica y Farmacia. Universidad Nacional del Sur.; 2009

Universidad Nacional del Sur

17b-estradiol is a steroid hormone that promotes cell survival and prevents from apoptosis in a great variety of tissues. Previous investigations with the murine skeletal muscle C2C12 cell line demonstrated that the action of 17b-estradiol involves stimulation of PI3K-Akt. Studies with other cell types have shown that upon its activation Akt can inhibit apoptosis by alternative mechanisms. In this report, we investigated whether the antiapoptotic effect of estrogen in muscle cells is mediated by Akt through interaction with and inhibition of ASK1, a MAPKKK pro-apoptotic protein. When proliferating C2C12 cells were treated with 17b-estradiol (10-8 M), ASK1 protein levels and JNK1/2 and c-JUN phosphorylation were decreased. On the other hand, treatment with the apoptotic agent H2O2 caused a sustained increase of JNK1/2 and c-JUN phosphorylation. Furthermore, a 17b-estradiol-dependent interaction between phospho-Akt and ASK1 was detected by coimmunoprecipitation. The association of both proteins was diminished by H2O2. In conclusion, these results suggest that Akt interaction with ASK1 followed by dephosphorylation of the latter is part of the mechanism by which 17b-estradiol exerts its antiapoptotic action in skeletal muscle cells challenged with stress stimuli.