Cellular thiols and reactive oxygen species in drug-induced apoptosis.
Cellular thiols and reactive oxygen species in drug-induced apoptosis.
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发表时间：
2001
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通讯作者：
W. Davis;Z. Ronai;K. Tew
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作者：
W. Davis;Z. Ronai;K. Tew
在高等真核生物中，活性氧（ROS）在线粒体呼吸过程中在分子氧还原过程中以及通过不同的酶系统产生。ROS参与多种细胞功能的调节，包括对病原体的防御、细胞内信号传导、转录激活、增殖和凋亡。细胞的还原-氧化（氧化还原）状态主要是细胞中存在的ROS和内源性硫醇缓冲剂（例如谷胱甘肽和硫氧还蛋白）水平之间精确平衡的结果，其保护细胞免受氧化损伤。ROS的急剧升高，超过内源性硫醇缓冲液水平的补偿性变化，可能导致信号传导途径的持续激活和诱导受影响细胞凋亡的基因表达。许多细胞毒性药物通过消除增殖信号选择性地杀死癌细胞，导致细胞死亡，并且许多报告已经证明，在用这些药物治疗后产生ROS。在这篇综述中，我们将总结最近的贡献，我们的理解的重要性细胞毒性药物诱导的细胞氧化还原状态的信号转导和转录导致激活的凋亡效应机制。
In higher eukaryotes, reactive oxygen species (ROS) are generated during respiration in mitochondria in the course of reduction of molecular oxygen as well as by distinct enzyme systems. ROS have been implicated in the regulation of diverse cellular functions including defense against pathogens, intracellular signaling, transcriptional activation, proliferation, and apoptosis. The reduction-oxidation (redox) state of the cell is primarily a consequence of the precise balance between the levels of ROS and endogenous thiol buffers present in the cell, such as glutathione and thioredoxin, which protect cells from oxidative damage. Dramatic elevation of ROS, exceeding compensatory changes in the level of the endogenous thiol buffers, may result in the sustained activation of signaling pathways and expression of genes that induce apoptosis in affected cells. Many cytotoxic drugs function selectively to kill cancer cells by the abrogation of proliferative signals, leading to cell death, and numerous reports have demonstrated that ROS are generated following treatment with these drugs. In this review, we will summarize recent contributions to our understanding of the importance of cytotoxic drug-induced modulation of cellular redox status for signaling and transcription leading to activation of apoptotic effector mechanisms.