Haddad John J
Severinghaus-Radiometer Research Laboratories, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA.
Int Immunopharmacol. 2004 Apr;4(4):475-93. doi: 10.1016/j.intimp.2004.02.002.
The mechanisms controlling apoptosis remain largely obscure. Because apoptosis is an integral part of the developmental program and is frequently the end-result of a temporal course of cellular events, it is referred to as programmed cell death. While there is considerable variation in the signals and requisite cellular metabolic events necessary to induce apoptosis in diverse cell types, the morphological features associated with apoptosis are highly conserved. Free radicals, particularly reactive oxygen species (ROS), have been proposed as common mediators for apoptosis. Many agents that induce apoptosis are either oxidants or stimulators of cellular oxidative metabolism. Conversely, many inhibitors of apoptosis have antioxidant activities or enhance cellular antioxidant defenses. Mammalian cells, therefore, exist in a state of oxidative siege in which survival requires an optimum balance of oxidants and antioxidants. The respiratory tract is subjected to a variety of environmental stresses, including oxidizing agents, particulates and airborne microorganisms that, together, may injure structural and functional lung components and thereby jeopardize the primary lung function of gas exchange. To cope with this challenge, the lung has developed elaborate defense mechanisms that include inflammatory-immune pathways as well as efficient antioxidant defense systems. In the absence of adequate antioxidant defenses, the damage produced is detected by the cell leading to the activation of genes responsible for the regulation of apoptosis, conceivably through stress-responsive transcription factors. Oxidative stress, in addition, may cause a shift in cellular redox state, which thereby modifies the nature of the stimulatory signal and which results in cell death as opposed to proliferation. ROS/redox modifications, therefore, may disrupt signal transduction pathways, can be perceived as abnormal and, under some conditions, may trigger apoptosis.
控制细胞凋亡的机制在很大程度上仍不清楚。由于细胞凋亡是发育程序的一个组成部分，并且经常是一系列细胞事件的最终结果，因此它被称为程序性细胞死亡。虽然在不同细胞类型中诱导细胞凋亡所需的信号和必要的细胞代谢事件存在很大差异，但与细胞凋亡相关的形态学特征却高度保守。自由基，特别是活性氧（ROS），已被认为是细胞凋亡的常见介质。许多诱导细胞凋亡的物质要么是氧化剂，要么是细胞氧化代谢的刺激剂。相反，许多细胞凋亡抑制剂具有抗氧化活性或增强细胞的抗氧化防御能力。因此，哺乳动物细胞处于一种氧化围攻状态，在这种状态下，细胞存活需要氧化剂和抗氧化剂之间的最佳平衡。呼吸道会受到多种环境压力的影响，包括氧化剂、颗粒物和空气传播的微生物，这些因素共同作用可能会损伤肺部的结构和功能成分，从而危及气体交换这一主要肺功能。为了应对这一挑战，肺已经发展出了复杂的防御机制，包括炎症免疫途径以及高效的抗氧化防御系统。在缺乏足够的抗氧化防御的情况下，细胞会检测到所产生的损伤，这可能会通过应激反应转录因子激活负责调节细胞凋亡的基因。此外，氧化应激可能会导致细胞氧化还原状态的改变，从而改变刺激信号的性质，导致细胞死亡而非增殖。因此，ROS/氧化还原修饰可能会破坏信号转导途径，被视为异常情况，并且在某些情况下可能会引发细胞凋亡。
