PKCdelta, ERK AND JNK IN 17beta-ESTRADIOL ANTIAPOPTOTIC ACTION IN C2C12 CELLS: EFFECTS ON COXIV AND MPTP

LA COLLA, ANABELA; PRONSATO LUCIA; RONDA ANA; MILANESI LORENA; RICADO BOLAND; VASCONSUELO ANDREA

Buenos Aires

Congreso; Reunión Anual de la Sociedad Argentina en Investigación Bioquímica y Biología Molecular; 2013

17beta-Estradiol (E2) protects several tissues from apoptosis, including skeletal muscle. Aging is characterized by a progressive loss of muscle mass and strength, pathology known as sarcopenia. This is associated to low hormone levels and deregulation of apoptosis. We have shown that E2 prevented apoptosis induced by H 2 O 2 in C2C12 skeletal muscle cells, acting on mitochondria. Although the main proteins mediating apoptosis are members of the Bcl-2 family and caspases, signaling molecules such as MAPKs and PKC, have been involved in its regulation. Here we studied further in depth the mechanism of action of E2 protecting C2C12 cells against apoptosis. We showed that E2 induced ERK translocation to mitochondria to regulate mitochondrial permeability transition pore (MPTP) and COXIV activity. We also demonstrated that H 2 O 2 stimulated the phosphorylation of PKCdelta in tyrosine 311, but pretreatment with E2 abrogated this activation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays showed that PKC inhibitors prevented apoptosis. Moreover, H 2 O 2 phosphorylated JNK in a time-dependent manner but preincubation with E2 suppressed this activation. PKC inhibition blocked JNK phosphorylation, suggesting that PKCdelta acts upstream of JNK. Our studies deepen the knowledge of the molecular basis of myophaties linked with deregulation of apoptosis by hormonal deficit states.