Linked Life Data

21368872

Source:http://linkedlifedata.com/resource/pubmed/id/21368872

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2011-3-3
pubmed:abstractText
The activation of nuclear factor kappa B (NF-?B) p50/RelA is a key event in ischemic neuronal injury, as well as in brain ischemic tolerance. We tested whether epigenetic mechanisms affecting the acetylation state of RelA might discriminate between neuroprotective and neurotoxic activation of NF-?B during ischemia. NF-?B activation and RelA acetylation were investigated in cortices of mice subjected to preconditioning brain ischemia or lethal middle cerebral artery occlusion (MCAO) and primary cortical neurons exposed to preconditioning or lethal oxygen-glucose deprivation (OGD). In mice subjected to MCAO and in cortical neurons exposed to lethal OGD, activated RelA displayed a high level of Lys310 acetylation in spite of reduced total acetylation. Also, acetylated RelA on Lys310 interacted strongly with the CREB-binding protein (CBP). Conversely, RelA activated during preconditioning ischemia appeared deacetylated on Lys310. Overexpressing RelA increased Bim promoter activity and neuronal cell death both induced by lethal OGD, whereas overexpressing the acetylation-resistant RelA-K310R, carrying a mutation from Lys310 to arginine, prevented both responses. Pharmacological manipulation of Lys310 acetylation by the sirtuin 1 activator resveratrol repressed the activity of the Bim promoter and reduced the neuronal cell loss. We conclude that the acetylation of RelA in Lys310 dictates NF-?B-dependent pro-apoptotic responses and represents a suitable target to dissect pathological from neuroprotective NF-?B activation in brain ischemia.
pubmed:commentsCorrections
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pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
2041-4889
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
e96
pubmed:dateRevised
2011-7-26
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The acetylation of RelA in Lys310 dictates the NF-?B-dependent response in post-ischemic injury.
pubmed:affiliation
Division of Pharmacology and Experimental Therapeutics, Department of Biomedical Sciences & Biotechnologies, School of Medicine, University of Brescia, Istituto Nazionale di Neuroscienze Brescia, Italy.
pubmed:publicationType
Journal Article
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