Mecanismos moleculares involucrados en el efecto protector del 17beta-estradiol y la testosterona frente a la apoptosis en celulas de musculo esqueletico.

PRONSATO, LUCIA; LA COLLA, ANABELA; VASCONSUELO, ANDREA; MILANESI, LORENA

Sierra de la Ventana

Congreso; Reunion anual de la AAOMM; 2015

AAOMM

The loss of muscle mass and strength is a prevalent condition among the elderly, known as sarcopenia. Although the molecular mechanisms underlying this condition are not fully clarified, accumulating evidence suggests that apoptosis could be responsible for the loss of myocytes in adulthood. Of relevance to our work, sarcopenia has been associated to sex hormone deficit, observed in old adults. Previously we have demonstrated the protective effect, at morphological, physiological, biochemical and molecular level, of both 17β-estradiol (E2) and Testosterone (T) against H2O2-induced apoptosis in C2C12 skeletal muscle cell line. It has been established that the exposure of these cells to H2O2 represents a comparable phenotype to aged skeletal muscle, constituting a useful tool for the study of sarcopenia. The aim of our research is to deepen the understanding of the molecular mechanisms involved in the antiapoptotic action of both hormones. We have observed that H2O2 treatment induces the mitochondrial permeability transition pore (mPTP) opening, p53 activation and the increase of RNAm p66Shc, phosphorylation and mitochondrial protein translocation, where it exerts its apoptotic action. We observed that H2O2 induces JNK, PKD, PKCθ, PKCδ and PKCI activation/phosphorylation, but not the PKCα/β2 one, acting some of these activated proteins, upstream of p66Shc apoptotic pathway. T or E2 treatment prior H2O2, reduces the mPTP opening and the levels of expression and/or phosphorylation of the proteins mentioned before. These results are in agreement with the observations indicating a protective effect of these steroids, and throw light on the knwlodgment of molecular mechanisms activated by each hormone to develop specific hormonal therapies.