S-nitrosylation inhibits protein kinase c-mediated contraction in mouse aorta

Hyehun Choi, Rita C. Tostes, R Clinton Webb

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

S-nitrosylation is a ubiquitous protein modification in redox-based signaling and forms S-nitrosothiol from nitric oxide (NO) on cysteine residues. Dysregulation of (S)NO signaling (nitrosative stress) leads to impairment of cellular function. Protein kinase C (PKC) is an important signaling protein that plays a role in the regulation of vascular function, and it is not known whether (S)NO affects PKC's role in vascular reactivity. We hypothesized that S-nitrosylation of PKC in vascular smooth muscle would inhibit its contractile activity. Aortic rings from male C57BL/6 mice were treated with auranofin or 1-chloro-2,4-dinitrobenzene (DNCB) as pharmacological tools, which lead to stabilize S-nitrosylation, and propylamine propylamine NONOate (PANOate) or S-nitrosocysteine (CysNO) as NO donors. Contractile responses of aorta to phorbol-12,13-dibutyrate, a PKC activator, were attenuated by auranofin, DNCB, PANOate, and CysNO. S-nitrosylation of PKCα was increased by auranofin or DNCB and CysNO as compared with control protein. Augmented S-nitrosylation inhibited PKCα activity and subsequently downstream signal transduction. These data suggest that PKC is inactivated by S-nitrosylation, and this modification inhibits PKC-dependent contractile responses. Because S-nitrosylation of PKC inhibits phosphorylation and activation of target proteins related to contraction, this posttranslational modification may be a key player in conditions of decreased vascular reactivity.

Original languageEnglish (US)
Pages (from-to)65-71
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume57
Issue number1
DOIs
StatePublished - Jan 1 2011

Fingerprint

Protein Kinases
Protein Kinase C
Aorta
Dinitrochlorobenzene
Propylamines
Auranofin
Blood Vessels
Nitric Oxide
Proteins
S-Nitrosothiols
Phorbol 12,13-Dibutyrate
Nitric Oxide Donors
Post Translational Protein Processing
Inbred C57BL Mouse
Vascular Smooth Muscle
Oxidation-Reduction
Cysteine
Signal Transduction
Phosphorylation
Pharmacology

Keywords

  • S-nitrosylation
  • protein kinase C
  • vascular contraction

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

S-nitrosylation inhibits protein kinase c-mediated contraction in mouse aorta. / Choi, Hyehun; Tostes, Rita C.; Webb, R Clinton.

In: Journal of Cardiovascular Pharmacology, Vol. 57, No. 1, 01.01.2011, p. 65-71.

Research output: Contribution to journalArticle

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