Source:http://linkedlifedata.com/resource/pubmed/id/11389192
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2001-6-4
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pubmed:abstractText |
Reperfusion after global brain ischemia results initially in a widespread suppression of protein synthesis in neurons, which persists in vulnerable neurons, that is caused by the inhibition of translation initiation as a result of the phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF2alpha). To identify kinases responsible for eIF2alpha phosphorylation [eIF2alpha(P)] during brain reperfusion, we induced ischemia by bilateral carotid artery occlusion followed by post-ischemic assessment of brain eIF2alpha(P) in mice with homozygous functional knockouts in the genes encoding the heme-regulated eIF2alpha kinase (HRI), or the amino acid-regulated eIF2alpha kinase (GCN2). A 10-fold increase in eIF2alpha(P) was observed in reperfused wild-type mice and in the HRI-/- or GCN2-/- mice. However, in all reperfused groups, the RNA-dependent protein kinase (PKR)-like endoplasmic reticulum eIF2alpha kinase (PERK) exhibited an isoform mobility shift on SDS-PAGE, consistent with the activation of the kinase. These data indicate that neither HRI nor GCN2 are required for the large increase in post-ischemic brain eIF2alpha(P), and in conjunction with our previous report that eIF2alpha(P) is produced in the brain of reperfused PKR-/- mice, provides evidence that PERK is the kinase responsible for eIF2alpha phosphorylation in the early post-ischemic brain.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-3042
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pubmed:author |
pubmed-author:AzamSS,
pubmed-author:CavenerD RDR,
pubmed-author:ChenJ JJJ,
pubmed-author:DeGraciaD JDJ,
pubmed-author:HaoBB,
pubmed-author:HardingH PHP,
pubmed-author:KrauseG SGS,
pubmed-author:KumarRR,
pubmed-author:OwenCC,
pubmed-author:RoyII,
pubmed-author:SullivanJ MJM,
pubmed-author:WhiteB CBC,
pubmed-author:ZhangPP
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pubmed:issnType |
Print
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pubmed:volume |
77
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1418-21
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11389192-Animals,
pubmed-meshheading:11389192-Brain Ischemia,
pubmed-meshheading:11389192-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:11389192-Enzyme Activation,
pubmed-meshheading:11389192-Fibroblasts,
pubmed-meshheading:11389192-Mice,
pubmed-meshheading:11389192-Mice, Knockout,
pubmed-meshheading:11389192-Phosphorylation,
pubmed-meshheading:11389192-Precipitin Tests,
pubmed-meshheading:11389192-Reperfusion Injury,
pubmed-meshheading:11389192-eIF-2 Kinase
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pubmed:year |
2001
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pubmed:articleTitle |
Brain ischemia and reperfusion activates the eukaryotic initiation factor 2alpha kinase, PERK.
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pubmed:affiliation |
Department of Emergency Medicine, Wayne State University, Detroit, Michigan 48201, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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