RT Journal Article
SR Electronic
T1 The Good, the Bad, and the Cell Type-Specific Roles of Hypoxia Inducible Factor-1α in Neurons and Astrocytes
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1988
OP 1993
DO 10.1523/JNEUROSCI.5323-07.2008
VO 28
IS 8
A1 Vangeison, Grace
A1 Carr, Dan
A1 Federoff, Howard J.
A1 Rempe, David A.
YR 2008
UL http://www.jneurosci.org/content/28/8/1988.abstract
AB Hypoxia inducible factor-1α (HIF-1α) is a key regulator of oxygen homeostasis, because it is responsible for the regulation of genes involved in glycolysis, erythropoiesis, angiogenesis, and apoptosis. In the CNS, HIF-1α is stabilized by insults associated with hypoxia and ischemia. Because its many target genes mediate both adaptive and pathological processes, the role of HIF-1α in neuronal survival is debated. Although neuronal HIF-1α function has been the topic of several studies, the role of HIF-1α function in astrocytes has received much less attention. To characterize the role of HIF-1α in neurons and astrocytes, we induced loss of HIF-1α function specifically in neurons, astrocytes, or both cell types in neuron/astrocyte cocultures exposed to hypoxia. Although loss of HIF-1α function in neurons reduced neuronal viability during hypoxia, selective loss of HIF-1 function in astrocytes markedly protected neurons from hypoxic-induced neuronal death. Although the pathological processes induced by HIF-1α in astrocytes remain to be defined, induction of inducible nitric oxide synthase likely contributes to the pathological process. This study delineates, for the first time, a cell type-specific action for HIF-1α within astrocytes and neurons.