QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, February 20, 2008, 28(8):1988-1993; doi:10.1523/JNEUROSCI.5323-07.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Vangeison, G. Articles by Rempe, D. A. PubMed PubMed Citation Articles by Vangeison, G. Articles by Rempe, D. A.

 Previous Article

Brief Communications
The Good, the Bad, and the Cell Type-Specific Roles of Hypoxia Inducible Factor-1 in Neurons and Astrocytes

Grace Vangeison,¹ Dan Carr,¹ Howard J. Federoff,² and David A. Rempe¹

¹Department of Neurology, Center for Neural Development and Disease, and Interdepartmental Graduate Program in Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, and ²Georgetown University Medical Center, Washington, DC 20057

Correspondence should be addressed to David A. Rempe, Center for Neural Development and Disease, Box 645, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642. Email: david_rempe{at}urmc.rochester.edu

Hypoxia inducible factor-1 (HIF-1) 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 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 in neuronal survival is debated. Although neuronal HIF-1 function has been the topic of several studies, the role of HIF-1 function in astrocytes has received much less attention. To characterize the role of HIF-1 in neurons and astrocytes, we induced loss of HIF-1 function specifically in neurons, astrocytes, or both cell types in neuron/astrocyte cocultures exposed to hypoxia. Although loss of HIF-1 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 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 within astrocytes and neurons.

Key words: HIF-1; astrocyte; neuron; hypoxia; ischemia; neurotoxicity

---

Received Aug. 20, 2007; revised Jan. 11, 2008; accepted Jan. 12, 2008.

Correspondence should be addressed to David A. Rempe, Center for Neural Development and Disease, Box 645, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642. Email: david_rempe{at}urmc.rochester.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help