Elevated peripheral blood mononuclear cell-derived superoxide production in healthy young black men
Elevated peripheral blood mononuclear cell-derived superoxide production in healthy young black men
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DOI：
10.1152/ajpheart.00784.2014
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发表时间：
2015-03-01
影响因子：
4.8
通讯作者：
Fadel, Paul J.
中科院分区：
文献类型：
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作者：
Deo, Shekhar H.;Holwerda, Seth W.;Fadel, Paul J.
多项研究表明，黑人的全身氧化应激水平较高。然而，导致氧化应激升高的来源和机制仍不清楚。鉴于外周血单核细胞 (PBMC) 可能是 NADPH 氧化酶衍生的超氧化物产生的主要来源，我们测试了以下假设：与白人相比，年轻黑人在 PBMC 中表现出更高的超氧化物产生和 NADPH 氧化酶表达。从血压正常的年轻黑人 (n = 18) 和白人 (n = 16) 男性的全血中新鲜分离出 PBMC。使用二氢乙锭荧光测量 PBMC 中细胞内超氧化物的产生，使用蛋白质印迹分析评估 PBMC 中 NADPH 氧化酶亚基、gp91(phox)（膜）和 p47(phox)（胞质）的蛋白表达，并测量血浆蛋白羰基作为全身氧化应激的标志物。黑人表现出细胞内超氧化物产量升高（4.3 +/- 0.5 vs. 2.0 +/- 0.6 相对荧光单位；黑人与白人相比，P < 0.05），gp91(phox) 和 p47(phox) 蛋白表达增加（例如，p47(phox)：1.1 +/- 0.2，黑人对比 0.4 +/- 0.1，白人，P < 0.05）的 PBMC 和更高的循环蛋白羰基水平（22 +/- 4 与 14 +/- 2 nmol/ml；黑人与白人，P < 0.05）。有趣的是，黑人男性高血压家族史并没有进一步增强 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，黑人表现出更多的静息 PBMC 衍生的超氧化物产生和 NADPH 氧化酶途径的上调，可能导致全身氧化应激增加。
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.