These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Peroxynitrite inhibits the expression of G(i)alpha protein and adenylyl cyclase signaling in vascular smooth muscle cells.
    Author: Bassil M, Li Y, Anand-Srivastava MB.
    Journal: Am J Physiol Heart Circ Physiol; 2008 Feb; 294(2):H775-84. PubMed ID: 18055527.
    Abstract:
    We previously showed that S-nitroso-N-acetylpenicillamine, a nitric oxide donor, decreased the levels and functions of G(i)alpha proteins by formation of peroxynitrite (ONOO(-)) in vascular smooth muscle cells (VSMC). The present studies were undertaken to investigate whether ONOO(-) can modulate the expression of G(i)alpha protein and associated adenylyl cyclase signaling in VSMC. Treatment of A-10 and aortic VSMC with ONOO(-) for 24 h decreased the expression of G(i)alpha-2 and G(i)alpha-3, but not G(s)alpha, protein in a concentration-dependent manner; expression was restored toward control levels by (111)Mn-tetralis(benzoic acid porphyrin) and uric acid, but not by 1H[1,2,4]oxadiazole[4,3-a]quinoxaline-1-one (ODQ) and KT-5823. cGMP levels were increased by approximately 50% and 150% by 0.1 and 0.5 mM ONOO(-), respectively, and attenuated toward control levels by ODQ. In addition, 0.5 mM ONOO(-) attenuated the inhibition of adenylyl cyclase by ANG II and C-type atrial natriuretic peptide (C-ANP(4-23)), as well as the inhibition of forskolin-stimulated adenylyl cyclase activity by GTPgammaS, whereas, the G(s)-mediated stimulations were augmented. In addition, 0.5 mM ONOO(-) decreased phosphorylation of ERK1/2 and p38 MAP kinase and enhanced JNK phosphorylation but did not affect AKT1/3 phosphorylation. These results suggest that ONOO(-) decreased the expression of G(i) proteins and associated functions in VSMC through a cGMP-independent mechanism and may involve the MAP kinase signaling pathway.
    [Abstract] [Full Text] [Related] [New Search]