Chemical induction of cellular antioxidants affords marked protection against oxidative injury in vascular smooth muscle cells
Chemical induction of cellular antioxidants affords marked protection against oxidative injury in vascular smooth muscle cells
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DOI：
10.1006/bbrc.2002.6614
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发表时间：
2002-03-22
影响因子：
3.1
通讯作者：
Li, YB
中科院分区：
文献类型：
--
作者：
Cao, ZX;Li, YB
大量证据表明，活性氧在动脉粥样硬化和心肌缺血再灌注损伤等心血管疾病的发病机制中起着关键作用。与这一概念一致，外源性抗氧化剂的管理已被证明对氧化性心血管损伤有保护作用。然而，化学诱导剂在血管中诱导内源性抗氧化剂是否也能保护血管细胞免受氧化损伤尚未得到广泛的研究。本研究以大鼠主动脉平滑肌A10细胞为体外系统，研究了独特的化学保护剂[H-3]-1,2-二硫孔-3-硫酮（D3T）对细胞抗氧化剂的诱导作用，以及D3T诱导的细胞抗氧化剂对氧化细胞损伤的保护作用。A10细胞与微摩尔浓度的D3T孵育24小时，导致细胞抗氧化剂电池以浓度依赖的方式显著诱导。这些包括还原性谷胱甘肽（GSH），谷胱甘肽过氧化物酶，谷胱甘肽还原酶，谷胱甘肽s -转移酶，超氧化物歧化酶和过氧化氢酶。为了进一步研究诱导的内源性抗氧化剂对氧化细胞损伤的保护作用，用D3T预处理A10细胞，然后暴露于黄嘌呤氧化酶(XO)/黄嘌呤、4-羟基壬烯醛或镉。我们观察到D3T预处理A10细胞对XO/黄嘌呤、4-羟基壬烯醛或镉诱导的细胞毒性有显著的保护作用，这是由3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四唑确定的。减少化验。综上所述，本研究首次证明，暴露于D3T可以诱导血管平滑肌细胞中的许多内源性抗氧化剂，并且这种细胞抗氧化剂的化学诱导伴随着对血管细胞氧化损伤的抵抗力显著增强。(C) 2002 Elsevier Science （USA）。
Extensive evidence suggests that reactive oxygen species are critically involved in the pathogenesis of cardiovascular diseases, such as atherosclerosis and myocardial ischemia-reperfusion injury. Consistent with this concept, administration of exogenous antioxidants has been shown to be protective against oxidative cardiovascular injury. However, whether induction of endogenous antioxidants by chemical inducers in vasculature also affords protection against oxidative vascular cell injury has not been extensively investigated. In this study, using rat aortic smooth muscle A10 cells as an in vitro system, we have studied the induction of cellular antioxidants by the unique chemoprotector, [H-3]-1,2-dithiole-3-thione (D3T) and the protective effects of the D3T-induced cellular antioxidants against oxidative cell injury. Incubation of A10 cells with micromolar concentrations of D3T for 24 h resulted in a significant induction of a battery of cellular antioxidants in a concentration-dependent manner. These included reduced glutathione (GSH), GSH peroxidase, GSSG reductase, GSH S-transferase, superoxide dismutase, and catalase. To further examine the protective effects of the induced endogenous antioxidants against oxidative cell injury, A10 cells were pretreated with D3T and then exposed to either xanthine oxidase (XO)/xanthine, 4-hydroxynonenal, or cadmium. We observed that D3T pretreatment of A10 cells led to significant protection against the cytotoxicity induced by XO/xanthine, 4-hydroxynonenal or cadmium, as determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium. reduction assay. Taken together, this study demonstrates for the first time that a number of endogenous antioxidants in vascular smooth muscle cells can be induced by exposure to D3T, and that this chemical induction of cellular antioxidants is accompanied by markedly increased resistance to oxidative vascular cell injury. (C) 2002 Elsevier Science (USA).