Skip Navigation LinksHome > January 2011 - Volume 57 - Issue 1 > S-nitrosylation Inhibits Protein Kinase C–mediated Contracti...
Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0b013e3181fef9cb
Original Article

S-nitrosylation Inhibits Protein Kinase C–mediated Contraction in Mouse Aorta

Choi, Hyehun MS; Tostes, Rita C PhD; Webb, R Clinton PhD

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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.

© 2011 Lippincott Williams & Wilkins, Inc.

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