BCL-2 is involved in preventing oxidant-induced cell death and in decreasing oxygen radical production
BCL-2 is involved in preventing oxidant-induced cell death and in decreasing oxygen radical production
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DOI：
10.1179/135100001101536535
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发表时间：
2001-01-01
期刊：
影响因子：
3.8
通讯作者：
Gutierrez, PL
中科院分区：
文献类型：
--
作者：
Amstad, PA;Liu, H;Gutierrez, PL
据推测，程序性细胞死亡是介导的，在一定程度上，通过自由基的形成，通过氧化途径。此外，已经提出BCL-2通过干扰由多种刺激诱导的氧衍生自由基的产生来抑制细胞死亡。为了检测BCL-2的抗氧化功能，我们用表达载体pD（5）-Neo-BCL-2转染小鼠表皮细胞JB 6 clone 41，并研究BCL-2过表达对氧化剂诱导的细胞死亡和活性氧产生的影响。与Neo对照细胞相比，表达BCL-2的细胞对由过氧化氢、超氧化物或由产生氧自由基的含醌化合物甲萘醌、二嗪醌和阿霉素诱导的杀伤和生长迟缓更具抗性。后一种化合物在生物还原代谢过程中产生活性氧。此外，暴露的细胞通过坏死而不是凋亡死亡。与对照Neo细胞相比，由含醌试剂产生的羟基自由基水平在BCL-2表达的JB 6细胞中较低。BCL-2，但是，不改变主要的细胞抗氧化酶超氧化物歧化酶，过氧化氢酶或谷胱甘肽过氧化物酶的活动。另一方面，在BCL-2过表达的细胞中，谷胱甘肽浓度在氧化攻击后增加，而对照细胞则相反。因此，我们的研究结果表明，BCL-2抑制氧化剂诱导的细胞死亡介导的，至少部分，通过抗氧化剂途径，这一途径涉及谷胱甘肽。
It has been hypothesized that programmed cell death is mediated, in part, through the formation of free radicals via oxidative pathways. Furthermore, it has been proposed that BCL-2 acts to inhibit cell death by interfering with the production of oxygen-derived free radicals induced by a wide variety of stimuli. In order to examine the antioxidant function of BCL-2, we transfected mouse epidermal cells JB6 clone 41 with the expression vector pD(5)-Neo-BCL-2 and studied the effect of BCL-2 overexpression on oxidant-induced cell death and on the production of reactive oxygen species. Compared to Neo control cells, BCL-2-expressing cells are more resistant to the killing and growth retardation induced by hydrogen peroxide, superoxide, or by the oxygen radical-generating quinone-containing compounds menadione, diaziquone and adriamycin. The latter compounds generate reactive oxygen species during bioreductive metabolism. In addition, the exposed cells die by necrosis rather than apoptosis. Hydroxyl radical levels generated by the quinone-containing agents were low in BCL-2-expressing JB6 cells compared to control Neo cells. BCL-2, however, does not change the activities of the major cellular antioxidant enzymes superoxide dismutase, catalase or glutathione peroxidase. On the other hand, the glutathione concentrations increased in BCL-2 overexpressing cells after oxidative challenge, while the opposite was true for control cells. Thus, our results suggest that BCL-2 inhibition of oxidant-induced cell death is mediated, at least in part, through an antioxidant pathway, and that this pathway involves glutathione.