p53 and p66 Proteins Compete for Hypoxia-Inducible Factor 1 Alpha Stabilization in Young and Old Rat Hearts Exposed to Intermittent Hypoxia

Abstract

The different responses to hypoxic challenge during life show that the young seem the most reactive and damaged, as is well documented by p53-mediated HIF-1alpha stabilization. The neonate, not showing any modification in terms of HIF-1alpha expression and activation, seems 'adapted' to such an environment, since it was maintained in hypoxia 3 days before and 8 days after birth. In the old, increasing p66 expression and tyrosine phosphorylation, probably exerting a slight HIF-1alpha stabilization in the two experimental conditions, provide evidence of longevity and oxidative stress resistance, as suggested by the low number of apoptotic events seen upon hypoxic challenge, and this fact could be due to impairment of oxygen-sensing mechanisms or to adaptation of the cells to apoptosis.