Linked Life Data

20353820

Source:http://linkedlifedata.com/resource/pubmed/id/20353820

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-8-4
pubmed:abstractText
Previous studies have shown that acute increases in oxidative stress induced by the addition of hydrogen peroxide (H(2)O(2)) can increase endothelial nitric oxide synthase (eNOS) catalytic activity via an increase in the phosphorylation of eNOS at serine 1177. However, it is unclear how increased H(2)O(2) affects nitric oxide (NO) signaling when endothelial cells are exposed to biomechanical forces. Thus, the purpose of this study was to evaluate the acute effects of H(2)O(2) on NO signaling in the presence or absence of laminar shear stress. We found that acute sustained increases in cellular H(2)O(2) levels in bovine aortic endothelial cells did not alter basal NO generation but the NO produced in response to shear stress was significantly increased. This amplification in NO signaling was found to correlate with an H(2)O(2)-induced increase in eNOS localized to the plasma membrane and an increase in total caveolin-1 protein levels. We further demonstrated that overexpressing caveolin-1 increased eNOS localized to the plasma membrane again without altering total eNOS protein levels. We also found that caveolin-1 overexpression increased NO generation in response to shear stress but only in the presence of H(2)O(2). Conversely, depleting caveolin-1 with an siRNA decreased eNOS localized to the plasma membrane and abolished the enhanced NO generation. Finally, we found that expressing a caveolin-1 binding-site deletion mutant of eNOS in COS-7 cells decreased its plasma membrane localization and resulted in attenuated NO production in response to calcium activation. In conclusion, we have identified a new role for caveolin-1 in enhancing eNOS trafficking to the plasma membrane that seems to be involved in priming eNOS for flow-mediated activation under conditions of oxidative stress. To our knowledge, this is the first report that H(2)O(2) modulates eNOS activity by altering its subcellular location and that caveolin-1 can play a stimulatory role in NO signaling.
pubmed:grant
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. Published by Elsevier Inc.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
159-70
pubmed:meshHeading
pubmed-meshheading:20353820-Animals, pubmed-meshheading:20353820-Binding Sites, pubmed-meshheading:20353820-COS Cells, pubmed-meshheading:20353820-Cattle, pubmed-meshheading:20353820-Caveolin 1, pubmed-meshheading:20353820-Cell Membrane, pubmed-meshheading:20353820-Cercopithecus aethiops, pubmed-meshheading:20353820-Endothelium, Vascular, pubmed-meshheading:20353820-Enzyme Activation, pubmed-meshheading:20353820-Hydrogen Peroxide, pubmed-meshheading:20353820-Nitric Oxide, pubmed-meshheading:20353820-Nitric Oxide Synthase Type III, pubmed-meshheading:20353820-Protein Transport, pubmed-meshheading:20353820-RNA, Small Interfering, pubmed-meshheading:20353820-Sequence Deletion, pubmed-meshheading:20353820-Shear Strength, pubmed-meshheading:20353820-Signal Transduction, pubmed-meshheading:20353820-Transgenes
pubmed:year
2010
pubmed:articleTitle
A novel role for caveolin-1 in regulating endothelial nitric oxide synthase activation in response to H2O2 and shear stress.
pubmed:affiliation
Pulmonary Vascular Disease Program, Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural