(PUBLICADO COMO RESUMEN) Role of androgen receptor in the protective action of testosterone during apoptosis in skeletal muscle

LUCÍA PRONSATO; RICARDO L. BOLAND; LORENA MILANESI

BONE

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2011 vol. 49 p. 1376 - 1376

8756-3282

(PUBLICADO COMO RESUMEN) Apoptosis occurs in response to environmental or developmental cues, cellular stresses and specific cell death signals. We have previously demonstrated that testosterone protects against H2O2-induced apoptosis in C2C12 muscle cells. Typical changes of apoptosis such as nuclear fragmentation, cytoskeleton disorganization, mitochondrial reorganization/dysfunction and cytochrome c release induced by H2O2, are abolished when cells are previously exposed to the hormone. Also, the molecular events activated, especially those that involve the mitochondria as a target, have begun to be elucidated. In the present work, we demonstrated not only a nonclassical localization of the androgen receptor (AR) but also its contribution to the anti-apoptotic effect of testosterone. Treatments with the AR antagonist, flutamide, prior to testosterone and H2O2 exposure, reduce the protective effect of the hormone.We confirmed it by the evaluation of the expression level, phosphorylation states and subcellular localization of ERK1/2 MAPKs, Akt, 14-3-3, members of the Bcl-2 family and PARP. The mitochondrial membrane potential was measured by flow cytometry, using the fluorescent dye JC-1. These studies showed the participation of AR in the protective role of testosterone. Moreover,we could demonstrate a nonclassical localization of AR in mitochondria and microdomains (caveolae and rafts) by competitive binding assays, immunocytochemistry and immunoblottings of subcellular fractions and gradient centrifugation. The results point to an active role of AR during the anti-apoptotic effect of testosterone at the nuclear (genomic response), mitochondrial (intrinsic pathway) and microsomal (response mediated by membrane proteins) levels.