HIF-1α cytoplasmic accumulation is associated with cell death in old rat cerebral cortex exposed to intermittent hypoxia

Intermittent hypoxia, followed by reoxygenation, determines the production of reactive oxygen species (ROS), which may lead to accelerated aging and to the appearance of age-related diseases. The rise in ROS levels might constitute a stress-stimulus activating specific redox-sensitive signalling pathways, so inducing either damaging or protective functions. Here, we report that in old rat cerebral cortex exposed to hypoxia, the accumulation in the cytoplasm of hypoxic inducible factor 1 alpha (HIF-1 alpha) - the master regulator of oxygen homeostasis - concomitant with p66(Shc) activation and reduced IkB alpha phosphorylation is associated with tissue apoptosis or necrosis. In young cerebral cortex, we hypothesize that the hypoxic damage may be reversible, based on our demonstration of elevated HIF-1 alpha levels, combined with a low level of IkB alpha phosphorylation, a decrease in IAP-1 and a lack of major change in Bc12 family proteins. These observations are associated with a low level of cell death induced by hypoxia, suggesting that HIF-1 alpha activation in cortical neurons may produce rescue proteins in response to intermittent hypoxia.