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|Title:||Peroxynitrite inhibits the expression of Giα protein and adenylyl cyclase signaling in vascular smooth muscle cells||Authors:||Bassil, Marcel
Anand-Srivastava, Madhu B.
|Affiliations:||Department of Medical Laboratory Sciences||Issue Date:||2008||Part of:||American journal of physiology-heart and circulatory physiology||Volume:||294||Issue:||2||Start page:||775||End page:||784||Abstract:||
We previously showed that S-nitroso-N-acetylpenicillamine, a nitric oxide donor, decreased the levels and functions of Giα 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 Giα protein and associated adenylyl cyclase signaling in VSMC. Treatment of A-10 and aortic VSMC with ONOO− for 24 h decreased the expression of Giα-2 and Giα-3, but not Gsα, protein in a concentration-dependent manner; expression was restored toward control levels by 111Mn-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 ∼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-ANP4–23), as well as the inhibition of forskolin-stimulated adenylyl cyclase activity by GTPγS, whereas, the Gs-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 Gi proteins and associated functions in VSMC through a cGMP-independent mechanism and may involve the MAP kinase signaling pathway.
|URI:||https://scholarhub.balamand.edu.lb/handle/uob/2381||Open URL:||Link to full text||Type:||Journal Article|
|Appears in Collections:||Department of Medical Laboratory Sciences|
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