INVESTIGADORES
MILANESI Lorena Magdalena
congresos y reuniones científicas
Título:
EFFECT OF TESTOSTERONE ON THE REGULATION OF PROTEIN AND GENE EXPRESSION RELATED TO OXIDATIVE STRESS DAMAGE IN C2C12 CELLS
Autor/es:
PRONSATO, LUCÍA; LA COLLA, ANABELA; ANDREA VASCONSUELO; BOLAND, RICARDO; MILANESI, LORENA
Lugar:
BsAs
Reunión:
Congreso; Reuniòn anual de la AAOMM; 2014
Institución organizadora:
AAOMM
Resumen:
The loss of muscle mass and strength with aging, also referred to as
sarcopenia, is a prevalent condition among the elderly, associated with a
deficit of sex hormones. In our previous works we have demonstrated that
testosterone protects against H2O2-induced apoptosis in
C2C12 at different levels: morphological, physiological, biochemical and
molecular. In the present study we evaluated some of the components upstream of
the classical apoptotic pathway which could trigger this response, the
expression levels of genes related to these pathways and the role of the
hormone during these events. By Western blot and immunocytochemistry, we
observed that H2O2 treatment induces the activation of
p53 in a time-dependent way. Phosphorylation of p53 induced by H2O2
is reduced by testosterone treatment prior to H2O2. One
of the ways that p53 induces apoptosis is through p66Shc activation, an adaptor
protein which amplifies the generation of mitochondrial hydrogen peroxide. Our
studies showed that hormone incubation prior to H2O2
reduces p66Shc activation and its mitochondrial localization. Furthermore, testosterone
diminished JNK phosphorylation induced by the apoptotic agent. So JNK could be
acting as a p66Shc activator, since pretreatment with a JNK inhibitor decreased
the phosphorylation not only of JNK but also of p66Shc. Finally, mRNA levels of
different pro and anti-apoptotic genes were determined by real time PCR, during
the apoptotic stimuli in presence or absence of the hormone, showing that
testosterone has opposite effects over gene expression to H2O2.
Testosterone would therefore favor the expression of genes related to proliferation
and survival respect of those associated to apoptosis.