Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri;
Department of Kinesiology, University of Texas at Arlington, Arlington, Texas.
Am J Physiol Heart Circ Physiol. 2015 Mar 1;308(5):H548-52. doi: 10.1152/ajpheart.00784.2014. Epub 2014 Dec 19.
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.
几项研究表明,黑人表现出全身性氧化应激升高。然而,导致氧化应激升高的原因和机制尚不清楚。鉴于外周血单核细胞(PBMCs)可能是 NADPH 氧化酶衍生超氧化物产生的主要来源,我们检验了一个假设,即年轻黑人男性的 PBMCs 中超氧化物产生和 NADPH 氧化酶表达高于白人。从年轻、血压正常的黑人(n=18)和白人(n=16)男性的全血中新鲜分离 PBMCs。使用二氢乙啶荧光法测量 PBMC 中的细胞内超氧化物产生,使用 Western blot 分析评估 PBMC 中 NADPH 氧化酶亚基 gp91(phox)(膜)和 p47(phox)(胞质)的蛋白表达,并且作为全身性氧化应激的标志物测量血浆蛋白羰基。黑人男性表现出更高的细胞内超氧化物产生(4.3±0.5 与 2.0±0.6 相对荧光单位;黑人男性与白人男性相比,P<0.05),PBMC 中 gp91(phox)和 p47(phox)的蛋白表达增加(例如,p47(phox):1.1±0.2,黑人男性与 0.4±0.1,白人男性,P<0.05),并且循环蛋白羰基水平更高(22±4 与 14±2 nmol/ml;黑人男性与白人男性相比,P<0.05)。有趣的是,黑人男性的高血压家族史并不能进一步增强 PBMC 衍生的细胞内超氧化物产生或 NADPH 氧化酶亚基蛋白表达。这些发现表明,黑人男性表现出更高的静息 PBMC 衍生超氧化物产生和 NADPH 氧化酶途径的上调,这可能导致全身性氧化应激增加。