title: Ambient ultrafine particles reduce endothelial nitric oxide production via S-glutathionylation of eNOS.
abstract: Exposure to airborne particulate pollutants is intimately linked to vascular oxidative stress and inflammatory responses with clinical relevance to atherosclerosis. Particulate matter (PM) has been reported to induce endothelial dysfunction and atherosclerosis. Here, we tested whether ambient ultrafine particles (UFP, diameter <200 nm) modulate eNOS activity in terms of nitric oxide (NO) production via protein S-glutathionylation. Treatment of human aortic endothelial cells (HAEC) with UFP significantly reduced NO production. UFP-mediated reduction in NO production was restored in the presence of JNK inhibitor (SP600125), NADPH oxidase inhibitor (Apocynin), anti-oxidant (N-acetyl cysteine), and superoxide dismutase mimetics (Tempol and MnTMPyP). UFP exposure increased the GSSG/GSH ratio and eNOS S-glutathionylation, whereas over-expression of Glutaredoxin-1 (to inhibit S-glutathionylation) restored UFP-mediated reduction in NO production by nearly 80%. Thus, our findings suggest that eNOS S-glutathionylation is a potential mechanism underlying ambient UFP-induced reduction of NO production.
authors.affiliation: Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, United States.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Du
authors.forename: Mohamad
authors.initials: M
authors.lastname: Navab
authors.forename: Melody
authors.initials: M
authors.lastname: Shen
authors.forename: James
authors.initials: J
authors.lastname: Hill
authors.forename: Payam
authors.initials: P
authors.lastname: Pakbin
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.forename: Tzung K
authors.initials: TK
authors.lastname: Hsiai
authors.forename: Rongsong
authors.initials: R
authors.lastname: Li
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D032701:Biomimetics; D002478:Cells, Cultured; D003497:Cyclic N-Oxides / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010316:Particle Size; D052638:Particulate Matter / Q000378:metabolism*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors; D000072105:Superoxide Dismutase-1
chemical_list: D000098:Acetophenones; D000873:Anthracenes; D003497:Cyclic N-Oxides; D008665:Metalloporphyrins; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; D052638:Particulate Matter; C000606290:SOD1 protein, human; D013113:Spin Labels; C432165:pyrazolanthrone; D009569:Nitric Oxide; C056165:acetovanillone; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019255:NADPH Oxidases; D005978:Glutathione; C001803:tempol
keywords: Air pollution; Endothelial dysfunction; Oxidative stress; S-glutathionylation; Ultrafine particles/UFP; eNOS