NEUROPROTECTIVE EFFECT OF THE ACTIVATION OF CREB AGAINST OXIDATIVE STRESS IN NEURONAL CELLS

PREGI N; CASTILLO DS; CÁNEPA ET

Potrero de los Funes, San Luis

Congreso; XLVII Reunión anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2011

SAIB

CREB (cAMP response element binding) protein is a cellular transcription factor that mediates responses to different physiological and pathological signals. Previously, we have demostrated that this transcription factor is phosphorylated in response to DNA damage and cellular stress caused by H2O2 treatment and that this modification seems to be necessary but not sufficient to trigger its activation. Here, we studied the role of CREB activation during the DNA damage response against neuronal stress. We observed an upregulation of CREB mRNA and protein levels (RealTimePCR and Western blot) following H2O2 treatment, but no significant ser133 phosporylation. Downregulation of CREB resulted in enhanced apoptosis (20,7% vs. 6,1%) and increased number and size of DNA damage foci as well as gamma H2Ax protein levels in neuronal cells treated with H2O2. The neuroprotective effect mediated by CREB appears to require phosphorylation at another residue, different from ser133, and to be regulated by different pathways. In summary, regulation and activation of CREB and its transcriptional modulation of target genes promote the neuroprotective effect of CREB.