Linked Life Data

20381604

Source:http://linkedlifedata.com/resource/pubmed/id/20381604

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-8-4
pubmed:abstractText
Ascent to high altitude is associated with tissue hypoxia resulting from the decrease in partial pressure of atmospheric oxygen. The hippocampus, in particular, is highly vulnerable to hypoxic insult, which at least in part can be attributed to the occurrence of glutamate excitotoxicity. Although this excitotoxic damage is often related to increased NMDA receptor activation and subsequent calcium-mediated free radical generation, the mechanisms involving the transcriptional regulation of NMDA receptor subunit expression by hypoxic stress remains to be explored. Our study reveals a novel mechanism for the regulation of expression of the NR1 subunit of NMDA receptors by the Sp family of transcription factors through an oxidative-stress-mediated mechanism that also involves the molecular chaperone Hsp90. The findings not only show the occurrence of lipid peroxidation and DNA damage in hippocampal cells exposed to hypoxia but also reveal a calcium-independent mechanism of selective oxidation and degradation of Sp3 by the 20S proteasome. This along with increased DNA binding activity of Sp1 leads to NR1 upregulation in the hippocampus during hypoxic stress. The study therefore provides evidence for free radical-mediated regulation of gene expression in hypoxia and the scope of the use of antioxidants in preventing excitotoxic neuronal damage during hypoxia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1873-4596
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
178-91
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Oxidative-stress-induced alterations in Sp factors mediate transcriptional regulation of the NR1 subunit in hippocampus during hypoxia.
pubmed:affiliation
Defence Institute of High Altitude Research, Leh, Ladakh, Jammu and Kashmir, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't