The antiapoptotic effect of 17ß-estradiol in skeletal muscle cells involves PKCδ, JNK and p66Shc (PUBLICADO COMO RESUMEN).

ANABELA LA COLLA; LUCÍA PRONSATO; LORENA MILANESI; RICARDO L. BOLAND; ANDREA VASCONSUELO

BONE

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2016 vol. 83 p. 282 - 282

8756-3282

The hormone 17β-Estradiol (E2) acts on several non-reproductive tissues,including skeletal muscle. We have shown that E2 at physiological concentrations prevented apoptosis induced by hydrogen peroxide (H2O2) in skeletal myoblasts. The present work further characterizes the signaling mechanisms modulated by E2, responsible for apoptosis inhibition in skeletal muscle cells. We found that H2O2 induces activation of PKCδ; and JNK in C2C12 cells. By TUNEL assays using specific inhibitors, we demonstrated that the H2O2-induced activation of PKCδ and JNK are necessary to trigger apoptosis in skeletal muscle cells. Moreover, immunological assays support the data that PKCδ acts upstream JNK. We observed that E2 inhibits the activation of these kinases, resulting in the inhibition of phosphorylation and translocation to mitochondria of the adaptor protein p66Shc associated to oxidative stress. Additionally, we found that E2 diminishes the H2O2-induced p66Shc messenger RNA (mRNA) level. Tetramethylrhodamine methyl ester (TMRM) staining showed that pretreatment with E2 conduces to protection of the mitochondrial membranepotential (Δψm) in line with the inhibition of p66Shc translocation to mitochondria. In agreement, by qRT-PCR we demonstrated that E2 diminishes the H2O2-induced mRNA levels of the apoptotic proteins PERP and Puma associated to Δψm loss, and increases those of the antiapoptotic protein Bcl-2. Our results provide basis for a putative mechanism by which E2 exerts beneficial effects on mitochondria, against oxidative stress, in skeletal muscle cells, helping to find new targets for the development of therapies for myophaties associated to deregulated apoptosis by hormonal deficits.