title: Elevated peripheral blood mononuclear cell-derived superoxide production in healthy young black men.
abstract: Several studies have demonstrated that blacks exhibit elevations in systemic oxidative stress. However, the source(s) and mechanism(s) contributing to the elevation in oxidative stress remain unclear. Given that peripheral blood mononuclear cells (PBMCs) can be a major source of NADPH oxidase-derived superoxide production, we tested the hypothesis that young black men demonstrate greater superoxide production and NADPH oxidase expression in PBMCs compared with whites. PBMCs were freshly isolated from whole blood in young normotensive black (n = 18) and white (n = 16) men. Intracellular superoxide production in PBMCs was measured using dihydroethidium fluorescence, protein expression of NADPH oxidase subunits, gp91(phox) (membranous) and p47(phox) (cytosolic) in PBMCs were assessed using Western blot analysis, and plasma protein carbonyls were measured as a marker of systemic oxidative stress. Black men showed elevated intracellular superoxide production (4.3 ± 0.5 vs. 2.0 ± 0.6 relative fluorescence units; black men vs. white men, P < 0.05), increased protein expression for gp91(phox) and p47(phox) (e.g., p47(phox): 1.1 ± 0.2, black men vs. 0.4 ± 0.1, white men, P < 0.05) in PBMCs and higher circulating protein carbonyl levels (22 ± 4 vs. 14 ± 2 nmol/ml; black men vs. white men, P < 0.05). Interestingly, a positive family history of hypertension in black men did not further enhance PBMC-derived intracellular superoxide production or NADPH oxidase subunit protein expression. These findings indicate that black men exhibit greater resting PBMC-derived superoxide production and an upregulation of the NADPH oxidase pathway with a possible contribution to increases in systemic oxidative stress.
authors.affiliation: Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri;
authors.forename: Shekhar H
authors.initials: SH
authors.lastname: Deo
authors.affiliation: Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri;
authors.forename: Seth W
authors.initials: SW
authors.lastname: Holwerda
authors.affiliation: Department of Kinesiology, University of Texas at Arlington, Arlington, Texas.
authors.forename: David M
authors.initials: DM
authors.lastname: Keller
authors.affiliation: Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri; Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri; and fadelp@health.missouri.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fadel
mesh_terms: D044383:Black People; D064368:Healthy Volunteers; D006801:Humans; D006973:Hypertension / Q000208:ethnology; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D009249:NADP / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D050050:Protein Carbonylation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000097:blood*; D044465:White People; D055815:Young Adult
chemical_list: D021122:Protein Subunits; D013481:Superoxides; D009249:NADP
keywords: hypertension; racial differences; reactive oxygen species