Open AccessHIF‐1α cytoplasmic accumulation is associated with cell death in old rat cerebral cortex exposed to intermittent hypoxia
Author(s) -
Rapino Cinzia,
Bianchi Giuseppina,
Di Giulio Camillo,
Centurione Lucia,
Cacchio Marisa,
Antonucci Adriano,
Cataldi Amelia
Publication year - 2005
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2005.00161.x
Subject(s) - biology , programmed cell death , hypoxia (environmental) , cerebral cortex , microbiology and biotechnology , phosphorylation , apoptosis , reactive oxygen species , homeostasis , cytoplasm , mitochondrion , downregulation and upregulation , regulator , oxidative stress , endocrinology , biochemistry , oxygen , chemistry , gene , organic chemistry
Summary 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 1α (HIF‐1α) – the master regulator of oxygen homeostasis – concomitant with p66 Shc activation and reduced IkBα 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‐1α levels, combined with a low level of IkBα phosphorylation, a decrease in IAP‐1 and a lack of major change in Bcl2 family proteins. These observations are associated with a low level of cell death induced by hypoxia, suggesting that HIF‐1α activation in cortical neurons may produce rescue proteins in response to intermittent hypoxia.