Circu Magdalena L, Aw Tak Yee
Department of Molecular & Cellular Physiology, Louisiana University Health Sciences Center, Shreveport, LA 71130, USA.
Biochim Biophys Acta. 2012 Oct;1823(10):1767-77. doi: 10.1016/j.bbamcr.2012.06.019. Epub 2012 Jun 23.
Apoptosis is a highly organized form of cell death that is important for tissue homeostasis, organ development and senescence. To date, the extrinsic (death receptor mediated) and intrinsic (mitochondria derived) apoptotic pathways have been characterized in mammalian cells. Reduced glutathione, is the most prevalent cellular thiol that plays an essential role in preserving a reduced intracellular environment. glutathione protection of cellular macromolecules like deoxyribose nucleic acid proteins and lipids against oxidizing, environmental and cytotoxic agents, underscores its central anti-apoptotic function. Reactive oxygen and nitrogen species can oxidize cellular glutathione or induce its extracellular export leading to the loss of intracellular redox homeostasis and activation of the apoptotic signaling cascade. Recent evidence uncovered a novel role for glutathione involvement in apoptotic signaling pathways wherein post-translational S-glutathiolation of protein redox active cysteines is implicated in the potentiation of apoptosis. In the present review we focus on the key aspects of glutathione redox mechanisms associated with apoptotic signaling that includes: (a) changes in cellular glutathione redox homeostasis through glutathione oxidation or GSH transport in relation to the initiation or propagation of the apoptotic cascade, and (b) evidence for S-glutathiolation in protein modulation and apoptotic initiation.
细胞凋亡是一种高度有序的细胞死亡形式，对组织稳态、器官发育和衰老至关重要。迄今为止，外在（死亡受体介导）和内在（线粒体衍生）凋亡途径已在哺乳动物细胞中得到表征。还原型谷胱甘肽是最普遍存在的细胞硫醇，在维持细胞内还原环境中起重要作用。谷胱甘肽对细胞大分子如脱氧核糖核酸、蛋白质和脂质具有保护作用，使其免受氧化、环境和细胞毒性剂的侵害，这突出了其核心的抗凋亡功能。活性氧和氮物种可氧化细胞内的谷胱甘肽或诱导其向细胞外输出，导致细胞内氧化还原稳态丧失并激活凋亡信号级联反应。最近的证据揭示了谷胱甘肽在凋亡信号通路中的新作用，其中蛋白质氧化还原活性半胱氨酸的翻译后S-谷胱甘肽化与凋亡的增强有关。在本综述中，我们重点关注与凋亡信号相关的谷胱甘肽氧化还原机制的关键方面，包括：（a）通过谷胱甘肽氧化或谷胱甘肽转运导致的细胞谷胱甘肽氧化还原稳态变化与凋亡级联反应的启动或传播的关系，以及（b）蛋白质调节和凋亡启动中S-谷胱甘肽化的证据。
