Source:http://linkedlifedata.com/resource/pubmed/id/12929137
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2003-8-20
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pubmed:abstractText |
Our previous study demonstrated that the inhibition of interleukin-1beta (IL-1beta) reduces ischemic brain injury; however, the molecular mechanism of the action of IL-1 in cerebral ischemia is unclear. We are investigating currently the role of NFkappaB during focal cerebral ischemia, using mutant mice deficient in the interleukin-1 converting enzyme gene (ICE KO) in a middle cerebral artery occlusion (MCAO) model. Adult male ICE KO and wild-type mice (n = 120) underwent up to 24 hr of permanent MCAO. Cytoplasmic phospho-NFkappaB/p65 expression in ischemic brain was examined using Western blot analysis and immunohistochemistry. NFkappaB DNA-binding activity was detected using electrophoretic mobility shift assay (EMSA). Furthermore, ICAM-1 expression was examined in both the ICE KO and wild-type mice (WT). Western blot analysis and immunostaining showed that the level of cytosolic phosphorylated NFkappaB/p65 increased after 2 and 4 hr of MCAO in WT mice; however, NFkappaB/p65 was significantly reduced after MCAO in the ICE KO mice (P < 0.05). EMSA showed that NFkappaB DNA-binding activity increased after MCAO in WT mice; but this effect was reduced in the ICE KO mice. The number of ICAM-1-positive vessels in the ischemic hemisphere was greatly attenuated in the ICE KO mice (P < 0.05), which paralleled the results of immunohistochemistry. Our results demonstrate that NFkappaB phosphorylation is reduced in ICE KO mice, suggesting that ICE or IL-1 are involved in early NFkappaB phosphorylation. Because cerebral ischemia induced infarction is significantly reduced in ICE KO mice, we conclude that early NFkappaB phosphorylation plays a disruptive role in the ischemic process.
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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 |
Sep
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pubmed:issn |
0360-4012
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2003 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
73
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
698-707
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12929137-Animals,
pubmed-meshheading:12929137-Blotting, Western,
pubmed-meshheading:12929137-Brain,
pubmed-meshheading:12929137-Brain Ischemia,
pubmed-meshheading:12929137-Caspase 1,
pubmed-meshheading:12929137-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:12929137-Immunohistochemistry,
pubmed-meshheading:12929137-Infarction, Middle Cerebral Artery,
pubmed-meshheading:12929137-Intercellular Adhesion Molecule-1,
pubmed-meshheading:12929137-Male,
pubmed-meshheading:12929137-Mice,
pubmed-meshheading:12929137-Mice, Knockout,
pubmed-meshheading:12929137-Mutation,
pubmed-meshheading:12929137-NF-kappa B,
pubmed-meshheading:12929137-Neurons,
pubmed-meshheading:12929137-Phosphorylation,
pubmed-meshheading:12929137-Protein Transport
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pubmed:year |
2003
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pubmed:articleTitle |
Early NFkappaB activation is inhibited during focal cerebral ischemia in interleukin-1beta-converting enzyme deficient mice.
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pubmed:affiliation |
Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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