| pubmed-article:21179168 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21179168 | lifeskim:mentions | umls-concept:C1801960 | lld:lifeskim |
| pubmed-article:21179168 | lifeskim:mentions | umls-concept:C0178539 | lld:lifeskim |
| pubmed-article:21179168 | lifeskim:mentions | umls-concept:C0542341 | lld:lifeskim |
| pubmed-article:21179168 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:21179168 | pubmed:issue | 7327 | lld:pubmed |
| pubmed-article:21179168 | pubmed:dateCreated | 2010-12-23 | lld:pubmed |
| pubmed-article:21179168 | pubmed:abstractText | Endothelial nitric oxide synthase (eNOS) is critical in the regulation of vascular function, and can generate both nitric oxide (NO) and superoxide (O(2)(•-)), which are key mediators of cellular signalling. In the presence of Ca(2+)/calmodulin, eNOS produces NO, endothelial-derived relaxing factor, from l-arginine (l-Arg) by means of electron transfer from NADPH through a flavin containing reductase domain to oxygen bound at the haem of an oxygenase domain, which also contains binding sites for tetrahydrobiopterin (BH(4)) and l-Arg. In the absence of BH(4), NO synthesis is abrogated and instead O(2)(•-) is generated. While NOS dysfunction occurs in diseases with redox stress, BH(4) repletion only partly restores NOS activity and NOS-dependent vasodilation. This suggests that there is an as yet unidentified redox-regulated mechanism controlling NOS function. Protein thiols can undergo S-glutathionylation, a reversible protein modification involved in cellular signalling and adaptation. Under oxidative stress, S-glutathionylation occurs through thiol-disulphide exchange with oxidized glutathione or reaction of oxidant-induced protein thiyl radicals with reduced glutathione. Cysteine residues are critical for the maintenance of eNOS function; we therefore speculated that oxidative stress could alter eNOS activity through S-glutathionylation. Here we show that S-glutathionylation of eNOS reversibly decreases NOS activity with an increase in O(2)(•-) generation primarily from the reductase, in which two highly conserved cysteine residues are identified as sites of S-glutathionylation and found to be critical for redox-regulation of eNOS function. We show that eNOS S-glutathionylation in endothelial cells, with loss of NO and gain of O(2)(•-) generation, is associated with impaired endothelium-dependent vasodilation. In hypertensive vessels, eNOS S-glutathionylation is increased with impaired endothelium-dependent vasodilation that is restored by thiol-specific reducing agents, which reverse this S-glutathionylation. Thus, S-glutathionylation of eNOS is a pivotal switch providing redox regulation of cellular signalling, endothelial function and vascular tone. | lld:pubmed |
| pubmed-article:21179168 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21179168 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21179168 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21179168 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21179168 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21179168 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21179168 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21179168 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21179168 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21179168 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21179168 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21179168 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21179168 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21179168 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21179168 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21179168 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21179168 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:21179168 | pubmed:issn | 1476-4687 | lld:pubmed |
| pubmed-article:21179168 | pubmed:author | pubmed-author:TalukderM A... | lld:pubmed |
| pubmed-article:21179168 | pubmed:author | pubmed-author:ZweierJay LJL | lld:pubmed |
| pubmed-article:21179168 | pubmed:author | pubmed-author:HemannCraigC | lld:pubmed |
| pubmed-article:21179168 | pubmed:author | pubmed-author:ChenYeong-Ren... | lld:pubmed |
| pubmed-article:21179168 | pubmed:author | pubmed-author:ChenChun-AnCA | lld:pubmed |
| pubmed-article:21179168 | pubmed:author | pubmed-author:DruhanLawrenc... | lld:pubmed |
| pubmed-article:21179168 | pubmed:author | pubmed-author:VaradharajSar... | lld:pubmed |
| pubmed-article:21179168 | pubmed:author | pubmed-author:ReyesLevy ALA | lld:pubmed |
| pubmed-article:21179168 | pubmed:author | pubmed-author:WangTse-YaoTY | lld:pubmed |
| pubmed-article:21179168 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21179168 | pubmed:day | 23 | lld:pubmed |
| pubmed-article:21179168 | pubmed:volume | 468 | lld:pubmed |
| pubmed-article:21179168 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21179168 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21179168 | pubmed:pagination | 1115-8 | lld:pubmed |
| pubmed-article:21179168 | pubmed:dateRevised | 2011-6-17 | lld:pubmed |
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| pubmed-article:21179168 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:21179168 | pubmed:articleTitle | S-glutathionylation uncouples eNOS and regulates its cellular and vascular function. | lld:pubmed |
| pubmed-article:21179168 | pubmed:affiliation | Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, Ohio State University, Columbus, Ohio 43210, USA. | lld:pubmed |
| pubmed-article:21179168 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21179168 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:21179168 | lld:pubmed |
