Hypoxia-inducible factor signaling mechanisms in the central nervous system

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Title: Hypoxia-inducible factor signaling mechanisms in the central nervous system
Authors: Corcoran, Alan
O'Connor, J. J.
Permanent link: http://hdl.handle.net/10197/4789
Date: 14-Jun-2013
Online since: 2013-10-22T07:58:41Z
Abstract: In the CNS neurons are highly sensitive to the availability of oxygen. In conditions where oxygen availability is decreased neuronal function can be altered, leading to injury and cell death. Hypoxia has been implicated in a number of central nervous system pathologies including stroke, head trauma, and neurodegenerative diseases. Depending on the duration and severity of the oxygen deprivation, cellular oxygen-sensor responses activate a variety of short- and long-term energy saving and cellular protection mechanisms.  Failure of synaptic transmission can be observed within minutes following this hypoxia. The acute affects of hypoxia on synaptic transmission are primarily mediated by altering ion fluxes across membranes, presynaptic effects of adenosine and other actions at glutamatergic receptors. A more long-term feature of the response of neurons to hypoxia is the activation of transcription factors such as hypoxia inducible factor. The activation of hypoxia inducible factor is governed by a family of dioxygenases called hypoxia inducible factor prolyl 4 hydroxylases (PHDs). Under hypoxic conditions, PHD activity is inhibited, thereby allowing hypoxia inducible factor to accumulate and translocate to the nucleus, where it binds to the hypoxia-responsive element sequences of target gene promoters. Inhibition of PHD activity stabilizes hypoxia inducible factor and other proteins thus acting as a neuroprotective agent. This review will focus on the response of neuronal cells to hypoxia inducible factor and its targets, including the prolyl hydroxylases. We also present evidence for acute effects of PHD inhibition on synaptic transmission and plasticity in the hippocampus.
Type of material: Journal Article
Publisher: John Wiley & Sons
Journal: Acta Physiologica
Volume: 208
Issue: 4
Start page: 298
End page: 310
Copyright (published version): 2013 Scandinavian Physiological Society
Keywords: AMPA receptorsHippocampusHypoxia-inducible factorLong-term potentiationProlyl hydroxylase domainSynaptic transmission
DOI: 10.1111/apha.12117
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection

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