Aging decreases expression and activity of glutathione peroxidase-1 in human endothelial progenitor cells
Aging decreases expression and activity of glutathione peroxidase-1 in human endothelial progenitor cells
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DOI：
10.1016/j.mvr.2009.08.009
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发表时间：
2009-12-01
影响因子：
3.1
通讯作者：
Katusic, Zvonimir S.
中科院分区：
文献类型：
--
作者：
He, Tongrong;Joyner, Michael J.;Katusic, Zvonimir S.
衰老对促血管生成内皮祖细胞（EPCs）功能影响的潜在机制尚不清楚。先前的研究表明，与成熟内皮细胞相比，人类内皮细胞表达高水平的抗氧化酶。在这里，我们假设衰老会损害EPCs的抗氧化能力。从健康青年（平均24岁）和老年人（平均72岁）的血液单个核细胞中获得所谓的“早期EPCs”。老年受试者EPCs中谷胱甘肽过氧化物酶-1（谷胱甘肽过氧化物酶-1，GPX1）蛋白水平和酶活性显著降低。青年和老年受试者血清硒水平无显著差异。增加细胞培养中硒的浓度也不影响GPX1的蛋白水平，提示老年受试者EPCs中GPX1的减少与硒无关。过氧化氢酶、锰超氧化物歧化酶（MnSOD）的表达。CuZnSOD不受老化影响。老年受试者的EPCs对H2O2诱导的氧化应激比年轻受试者的EPCs更敏感，提示衰老过程中GPX1的损伤可能导致EPCs在氧化应激下的生存能力较低。结果表明，GPX1可能是增强老年受试者EPCs再生能力的潜在治疗靶点。(C) 2009爱思唯尔公司版权所有。
The mechanisms underlying effects of aging on functions of pro-angiogenic endothelial progenitor cells (EPCs) are poorly understood. Previous studies demonstrated that human EPCs express high levels of antioxidant enzymes as compared to mature endothelial cells. Here, we hypothesized that aging impairs antioxidant capacity of EPCs. So called "early EPCs" derived from cultured blood mononuclear cells were obtained from healthy young (average = 24 years old) and old (average = 72 years old) subjects. In EPCs of old subjects, the levels of glutathione peroxidase-1 (GPX1) protein and enzymatic activity were significantly reduced. The serum selenium levels in young and old subjects were not significantly different. Increasing selenium concentration in the cell culture also did not affect the protein levels of GPX1, suggesting the reduced GPX1 in old subject's EPCs is selenium independent. Expressions of catalase, Mn-superoxide dismutase (MnSOD). and CuZnSOD were not affected by aging. EPCs of old subjects were more sensitive to oxidative stress induced by H2O2 as compared with EPCs of young subjects, suggesting that impairment of GPX1 during aging may contribute to low survival ability of EPCs in response to oxidative stress. The results indicate that GPX1 may represent a potential therapeutic target for enhancement of regenerative capacity of EPCs in old subjects. (C) 2009 Elsevier Inc. All rights reserved.