Linked Life Data

19114587

Source:http://linkedlifedata.com/resource/pubmed/id/19114587

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-3-19
pubmed:abstractText
Dysfunction of vascular nitric oxide (NO)/cGMP signaling is believed to contribute essentially to various cardiovascular disorders. Besides synthesis and/or bioavailability of endothelial NO, impaired function of soluble guanylate cyclase (sGC) may play a key role in vascular dysfunction. Based on the proposal that desensitization of sGC through S-nitrosation contributes to vascular NO resistance ( Proc Natl Acad Sci U S A 104: 12312-12317, 2007 ), we exposed purified sGC to dinitrosyl iron complexes (DNICs), known as potent nitrosating agents. In the presence of 2 mM GSH, DNICs stimulated cGMP formation with EC(50) values of 0.1 to 0.5 microM and with an efficacy of 70 to 80% of maximal activity measured with 10 microM 2,2-diethyl-1-nitroso-oxyhydrazine (DEA/NO). In the absence of GSH, the efficacy of DNICs was markedly reduced, and sGC stimulation was counteracted by the inhibition of both basal and DEA/NO-stimulated cGMP formation at higher DNIC concentrations. Inactivation of sGC was slowly reversed in the presence of 2 mM GSH and associated with stoichiometric S-nitrosation of the protein (2.05 +/- 0.18 mol S-nitrosothiol per mol of 143-kDa heterodimer). S-Nitrosoglutathione and sodium nitroprusside caused partial inhibition of DEA/NO-stimulated sGC that was prevented by GSH, whereas nitroglycerin (0.3 mM) had no effect. Our findings indicate that nitrosation of two cysteine residues in sGC heterodimers results in enzyme inactivation. Protection by physiologically relevant concentrations of GSH (10 microM to 3 mM) suggests that S-nitrosation of sGC may contribute to vascular dysfunction in inflammatory disorders associated with nitrosative and oxidative stress and GSH depletion.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1521-0111
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
75
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
886-91
pubmed:dateRevised
2011-4-6
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Inactivation of soluble guanylate cyclase by stoichiometric S-nitrosation.
pubmed:affiliation
Department of Pharmacology and Toxicology, Karl-Franzens-Universität Graz, Universitätsplatz 2, A-8010 Graz, Austria. mayer@uni-graz.at
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't