Source:http://linkedlifedata.com/resource/pubmed/id/20501440
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2010-5-26
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| pubmed:abstractText |
Endothelin-1 (ET-1) plays a key role in the regulation of endothelial nitric oxide synthase (eNOS) activation in liver sinusoidal endothelial cells (LSECs). In the presence of endotoxin, an increase in caveolin-1 (Cav-1) expression impairs ET-1/eNOS signaling; however, the molecular mechanism is unknown. The objective of this study was to investigate the molecular mechanism of Cav-1 in the regulation of LPS suppression of ET-1-mediated eNOS activation in LSECs by examining the effect of caveolae disruption using methyl-beta-cyclodextrin (CD) and filipin. Treatment with 5 mM CD for 30 min increased eNOS activity (+255%, P < 0.05). A dose (0.25 microg/ml) of filipin for 30 min produced a similar effect (+111%, P < 0.05). CD induced the perinuclear localization of Cav-1 and eNOS and stimulated NO production in the same region. Readdition of 0.5 mM cholesterol to saturate CD reversed these effects. Both the combined treatment with CD and ET-1 (CD + ET-1) and with filipin and ET-1 stimulated eNOS activity; however, pretreatment with endotoxin (LPS) abrogated these effects. Following LPS pretreatment, CD + ET-1 failed to stimulate eNOS activity (+51%, P > 0.05), which contributed to the reduced levels of eNOS-Ser1177 phosphorylation and eNOS-Thr495 dephosphorylation, the LPS/CD-induced overexpression and translocation of Cav-1 in the perinuclear region, and the increased perinuclear colocalization of eNOS with Cav-1. These results supported the hypothesis that Cav-1 mediates the action of endotoxin in suppressing ET-1-mediated eNOS activation and demonstrated that the manipulation of caveolae produces significant effects on ET-1-mediated eNOS activity in LSECs.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anticholesteremic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cav protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Caveolin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Endotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Filipin,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type III,
http://linkedlifedata.com/resource/pubmed/chemical/Nos3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Cyclodextrins,
http://linkedlifedata.com/resource/pubmed/chemical/methyl-beta-cyclodextrin
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
1522-1547
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
297
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
G930-9
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| pubmed:dateRevised |
2010-11-2
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| pubmed:meshHeading |
pubmed-meshheading:20501440-Animals,
pubmed-meshheading:20501440-Anticholesteremic Agents,
pubmed-meshheading:20501440-Caveolae,
pubmed-meshheading:20501440-Caveolin 1,
pubmed-meshheading:20501440-Cell Membrane,
pubmed-meshheading:20501440-Cells, Cultured,
pubmed-meshheading:20501440-Cholesterol,
pubmed-meshheading:20501440-Cytoplasm,
pubmed-meshheading:20501440-Endothelial Cells,
pubmed-meshheading:20501440-Endothelin-1,
pubmed-meshheading:20501440-Endotoxins,
pubmed-meshheading:20501440-Filipin,
pubmed-meshheading:20501440-Liver,
pubmed-meshheading:20501440-Male,
pubmed-meshheading:20501440-Models, Biological,
pubmed-meshheading:20501440-Nitric Oxide,
pubmed-meshheading:20501440-Nitric Oxide Synthase Type III,
pubmed-meshheading:20501440-Nuclear Envelope,
pubmed-meshheading:20501440-Phosphorylation,
pubmed-meshheading:20501440-Protein Binding,
pubmed-meshheading:20501440-Protein Transport,
pubmed-meshheading:20501440-Rats,
pubmed-meshheading:20501440-Rats, Sprague-Dawley,
pubmed-meshheading:20501440-beta-Cyclodextrins
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| pubmed:year |
2009
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| pubmed:articleTitle |
Caveolin-1 mediates endotoxin inhibition of endothelin-1-induced endothelial nitric oxide synthase activity in liver sinusoidal endothelial cells.
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| pubmed:affiliation |
Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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