Participation of HSP27 in the antiapoptotic action of 17beta-estradiol in skeletal muscle cells.
Exposure to 17beta-estradiol prior to induction of apoptosis protects skeletal muscle cells against damage. The mechanism involved in this protective action of the hormone is poorly understood. In the present study, using the murine muscle cell line C2C12, evidence was obtained that inhibition of H(2)O(2)-induced apoptosis by the estrogen requires the participation of heat shock protein 27 (HSP27). Reverse transcriptase polymerase chain reaction, Western blot, and immunocytochemistry assays showed that 17beta-estradiol induces a time-dependent (5-60 min) increase in the expression of HSP27. In addition, in presence of quercetin, an inhibitor of HSPs, the antiapoptotic effect of the hormone was diminished. More specifically, blockage experiments with short interference RNA targeting HSP27 confirmed the role of this chaperone in the protective effect of the steroid. 17beta-Estradiol abolished caspase-3 cleavage elicited by H(2)O(2). Coimmunoprecipitation assays suggested physical interaction of HSP27 with caspase-3 in presence of estradiol. Furthermore, we observed that this chaperone interacts with estrogen receptors (ER) beta in mitochondria. Then, this study suggests that HSP27 plays a new role in the antiapoptotic action triggered by 17beta-estradiol by modulating caspase-3 activity and stabilizing ERbeta in skeletal muscle cells.
Vasconsuelo
Andrea
A
Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Bahía Blanca, Argentina. avascon@criba.edu.ar
Milanesi
Lorena
L
Boland
Ricardo
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004958:Estradiol / Q000378:metabolism*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics
D055551:HSP27 Heat-Shock Proteins; C486699:Hspb2 protein, mouse; D034741:RNA, Small Interfering; D004958:Estradiol; D006861:Hydrogen Peroxide; D053148:Caspase 3