17beta-Estradiol negatively regulates Bax proapoptotic actions in skeletal muscle cells

ANA CAROLINA RONDA; ANABELA LA COLLA; GASTÓN STOCKMAN; RICARDO BOLAND; ANDREA VASCONSUELO

Buenos Aires, Argentina

Congreso; XXVII AAOMM REUNIÓN ANUAL; 2010

Asociacion Argentina de Osteologia y Metabolismo Mineral

It is known that estrogens exert actions in skeletal muscle. Degenerative pathologies of the muscle mass, like sarcopenia, observed in menopausic women are due to decreased estrogen levels. Likewise, this hormone is important in the improvement of the muscular mass in cases of atrophy. Although the mechanisms underlying sarcopenia are far for being clarified, evidence suggests that an age-related acceleration of myocyte loss via apoptosis might represent a mechanism responsible for muscle decline. Furthermore, increased levels of apoptosis have also been reported in old rats undergoing muscle atrophy. We have previously demonstrated that 17beta-estradiol (E2) inhibits apoptosis in skeletal muscle cells. Here, we show that the proapoptotic protein Bax binds to the cytoplasmic protein 14-3-3 and ERK. Upon E2 treatment Bax/14-3-3 interaction is increased while Bax/ERK complex is diminished in agreement with E2 induced-ERK translocation to mitochondria. Apoptotic stimulation with hydrogen peroxide disrupts Bax/14-3-3 association and increases Bax/ERK interaction and these effects are reversed by E2 pretreatment. Moreover, flow cytometry studies show that the apoptotic stimulus induces a decrease in mitochondrial membrane potential, a change which is prevented by preincubation with E2. These findings suggest that Bax is involved in negative regulation of muscle apoptosis by E2 affecting mitochondrial function.