Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 8, Pages 1988-1993Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5323-07.2008
Keywords
HIF-1; astrocyte; neuron; hypoxia; ischemia; neurotoxicity
Categories
Funding
- NINDS NIH HHS [1P01NS050315, K08 NS046633, P01 NS050315, 5K08NS046633, 1R01NS054192, R01 NS054192] Funding Source: Medline
Ask authors/readers for more resources
Hypoxia inducible factor-1 alpha (HIF-1 alpha) 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-1 alpha is stabilized by insults associated with hypoxia and ischemia. Because its many target genes mediate both adaptive and pathological processes, the role of HIF-1 alpha in neuronal survival is debated. Although neuronal HIF-1 alpha function has been the topic of several studies, the role of HIF-1 alpha function in astrocytes has received much less attention. To characterize the role of HIF-1 alpha in neurons and astrocytes, we induced loss of HIF-1 alpha function specifically in neurons, astrocytes, or both cell types in neuron/astrocyte cocultures exposed to hypoxia. Although loss of HIF-1 alpha 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-1 alpha 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-1 alpha within astrocytes and neurons.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available