| Regulation of endothelial nitric-oxide synthase (NOS) S-glutathionylation by neuronal NOS: evidence of a functional interaction between myocardial constitutive NOS isoforms. | |
| | |
MedLine Citation:
|
PMID: 23091050 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Myocardial constitutive No production depends on the activity of both endothelial and neuronal NOS (eNOS and nNOS, respectively). Stimulation of myocardial β(3)-adrenergic receptor (β(3)-AR) produces a negative inotropic effect that is dependent on eNOS. We evaluated whether nNOS also plays a role in β(3)-AR signaling and found that the β(3)-AR-mediated reduction in cell shortening and [Ca(2+)](i) transient amplitude was abolished both in eNOS(-/-) and nNOS(-/-) left ventricular (LV) myocytes and in wild type LV myocytes after nNOS inhibition with S-methyl-L-thiocitrulline. LV superoxide (O(2)(·-)) production was increased in nNOS(-/-) mice and reduced by L-N(ω)-nitroarginine methyl ester (L-NAME), indicating uncoupling of eNOS activity. eNOS S-glutathionylation and Ser-1177 phosphorylation were significantly increased in nNOS(-/-) myocytes, whereas myocardial tetrahydrobiopterin, eNOS Thr-495 phosphorylation, and arginase activity did not differ between genotypes. Although inhibitors of xanthine oxidoreductase (XOR) or NOX2 NADPH oxidase caused a similar reduction in myocardial O(2)(·-), only XOR inhibition reduced eNOS S-glutathionylation and Ser-1177 phosphorylation and restored both eNOS coupled activity and the negative inotropic and [Ca(2+)](i) transient response to β(3)-AR stimulation in nNOS(-/-) mice. In summary, our data show that increased O(2)(·-) production by XOR selectively uncouples eNOS activity and abolishes the negative inotropic effect of β(3)-AR stimulation in nNOS(-/-) myocytes. These findings provide unequivocal evidence of a functional interaction between the myocardial constitutive NOS isoforms and indicate that aspects of the myocardial phenotype of nNOS(-/-) mice result from disruption of eNOS signaling. |
| | |
Authors:
|
Winifred O Idigo; Svetlana Reilly; Mei Hua Zhang; Yin Hua Zhang; Raja Jayaram; Ricardo Carnicer; Mark J Crabtree; Jean-Luc Balligand; Barbara Casadei |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-10-22 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 287 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2012 Dec |
Date Detail:
|
Created Date: 2012-12-24 Completed Date: 2013-02-26 Revised Date: 2013-04-16 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 43665-73 Citation Subset: IM |
Affiliation:
|
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Arginase / genetics, metabolism Calcium Signaling / drug effects, physiology* Citrulline / analogs & derivatives, pharmacology Enzyme Inhibitors / pharmacology Heart Ventricles / cytology, enzymology Isoenzymes / antagonists & inhibitors, genetics, metabolism Membrane Glycoproteins / genetics, metabolism Mice Mice, Knockout Muscle Proteins / antagonists & inhibitors, genetics, metabolism* Myocardium / cytology, enzymology* Myocytes, Cardiac / cytology, enzymology* NADPH Oxidase / genetics, metabolism NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide Synthase Type I / antagonists & inhibitors, genetics, metabolism* Nitric Oxide Synthase Type III / antagonists & inhibitors, genetics, metabolism* Phosphorylation / drug effects, physiology Receptors, Adrenergic, beta-3 / genetics, immunology Superoxides / metabolism Thiourea / analogs & derivatives, pharmacology Xanthine Dehydrogenase / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
//British Heart Foundation; //Wellcome Trust |
| Chemical | |
Reg. No./Substance:
|
0/Enzyme Inhibitors; 0/Isoenzymes; 0/Membrane Glycoproteins; 0/Muscle Proteins; 0/Receptors, Adrenergic, beta-3; 11062-77-4/Superoxides; 156719-41-4/S-methylthiocitrulline; 372-75-8/Citrulline; 50903-99-6/NG-Nitroarginine Methyl Ester; 62-56-6/Thiourea; EC 1.14.13.39/Nitric Oxide Synthase Type I; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos1 protein, mouse; EC 1.14.13.39/Nos3 protein, mouse; EC 1.17.1.4/Xanthine Dehydrogenase; EC 1.6.3.1/Cybb protein, mouse; EC 1.6.3.1/NADPH Oxidase; EC 3.5.3.1/Arginase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Prevalence and Presentation of Externalized Conductors and Electrical Abnormalities in Riata Defibri...
Next Document: Crystal structure of bovine coronavirus spike protein lectin domain.