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Dynamic denitrosylation via S-nitrosoglutathione reductase regulates cardiovascular function.

Publication ,  Journal Article
Beigi, F; Gonzalez, DR; Minhas, KM; Sun, Q-A; Foster, MW; Khan, SA; Treuer, AV; Dulce, RA; Harrison, RW; Saraiva, RM; Premer, C; Schulman, IH ...
Published in: Proc Natl Acad Sci U S A
March 13, 2012

Although protein S-nitrosylation is increasingly recognized as mediating nitric oxide (NO) signaling, roles for protein denitrosylation in physiology remain unknown. Here, we show that S-nitrosoglutathione reductase (GSNOR), an enzyme that governs levels of S-nitrosylation by promoting protein denitrosylation, regulates both peripheral vascular tone and β-adrenergic agonist-stimulated cardiac contractility, previously ascribed exclusively to NO/cGMP. GSNOR-deficient mice exhibited reduced peripheral vascular tone and depressed β-adrenergic inotropic responses that were associated with impaired β-agonist-induced denitrosylation of cardiac ryanodine receptor 2 (RyR2), resulting in calcium leak. These results indicate that systemic hemodynamic responses (vascular tone and cardiac contractility), both under basal conditions and after adrenergic activation, are regulated through concerted actions of NO synthase/GSNOR and that aberrant denitrosylation impairs cardiovascular function. Our findings support the notion that dynamic S-nitrosylation/denitrosylation reactions are essential in cardiovascular regulation.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 13, 2012

Volume

109

Issue

11

Start / End Page

4314 / 4319

Location

United States

Related Subject Headings

  • Vasodilation
  • Ryanodine Receptor Calcium Release Channel
  • Receptors, Adrenergic, beta
  • Protein Transport
  • Nitrosation
  • Nitric Oxide Synthase
  • Myocytes, Cardiac
  • Myocardium
  • Myocardial Contraction
  • Mice, Inbred C57BL
 

Citation

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MLA
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Beigi, F., Gonzalez, D. R., Minhas, K. M., Sun, Q.-A., Foster, M. W., Khan, S. A., … Hare, J. M. (2012). Dynamic denitrosylation via S-nitrosoglutathione reductase regulates cardiovascular function. Proc Natl Acad Sci U S A, 109(11), 4314–4319. https://doi.org/10.1073/pnas.1113319109
Beigi, Farideh, Daniel R. Gonzalez, Khalid M. Minhas, Qi-An Sun, Matthew W. Foster, Shakil A. Khan, Adriana V. Treuer, et al. “Dynamic denitrosylation via S-nitrosoglutathione reductase regulates cardiovascular function.Proc Natl Acad Sci U S A 109, no. 11 (March 13, 2012): 4314–19. https://doi.org/10.1073/pnas.1113319109.
Beigi F, Gonzalez DR, Minhas KM, Sun Q-A, Foster MW, Khan SA, et al. Dynamic denitrosylation via S-nitrosoglutathione reductase regulates cardiovascular function. Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4314–9.
Beigi, Farideh, et al. “Dynamic denitrosylation via S-nitrosoglutathione reductase regulates cardiovascular function.Proc Natl Acad Sci U S A, vol. 109, no. 11, Mar. 2012, pp. 4314–19. Pubmed, doi:10.1073/pnas.1113319109.
Beigi F, Gonzalez DR, Minhas KM, Sun Q-A, Foster MW, Khan SA, Treuer AV, Dulce RA, Harrison RW, Saraiva RM, Premer C, Schulman IH, Stamler JS, Hare JM. Dynamic denitrosylation via S-nitrosoglutathione reductase regulates cardiovascular function. Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4314–4319.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 13, 2012

Volume

109

Issue

11

Start / End Page

4314 / 4319

Location

United States

Related Subject Headings

  • Vasodilation
  • Ryanodine Receptor Calcium Release Channel
  • Receptors, Adrenergic, beta
  • Protein Transport
  • Nitrosation
  • Nitric Oxide Synthase
  • Myocytes, Cardiac
  • Myocardium
  • Myocardial Contraction
  • Mice, Inbred C57BL