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Title: Effects of oxidative stress on the expression and function of inducible nitric oxide synthase (iNOS) in cultured vascular smooth muscle cells
Author: Bingi, Praveen Kumar
ISNI:       0000 0004 6061 1380
Awarding Body: University of Hertfordshire
Current Institution: University of Hertfordshire
Date of Award: 2015
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The role of inducible nitric oxide synthase (iNOS) and/or nitric oxide (NO) in atherosclerosis remains elusive. Several researchers argued whether iNOS and/or NO are pathogenic or cardio protective. The pathogenesis of atherosclerosis is complex and includes mechanisms associated with inducible nitric oxide synthase (iNOS). We have demonstrated that the expression and function of iNOS may be selectively down regulated by pro-oxidants such as antimycin A and diethyl maleate (DEM). To further explore the underlying mechanisms associated with these effects we have investigated whether antimycin A and/or DEM modulated the activation of key cellular signalling molecules associated with the induction of iNOS. Expression of p38 mitogen activated kinase (MAPK) and Akt were induced by exposure to lipopolysaccharide (LPS) and interferon-gamma (IFN-γ). Oxidative stress (OS) was induced using antimycin A, DEM and hydrogen peroxide (H2O2). All three OS inducers caused a significant generation of free radicals whereas only antimycin A and DEM generated superoxide radical (O2-). Also nitrite production and iNOS expression may be down regulated, in part; by pro-oxidants generating O2- but not hydroxyl radicals (OH-). Antimycin A and DEM concentration dependently inhibited the phosphorylation of p38 MAPK and Akt and this was restored when the cells were pre-treated with Atorvastatin whereas H2O2 was without any significant effect. Taken together, the data suggest novel actions for both pro-oxidants and atorvastatin which may have important implications in coronary artery disease where suppression of iNOS may be deleterious and maintaining its expression may be cardio-protective.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: nitric oxide ; oxidative stress ; iNOS ; atherosclerosis ; statins ; free radicals