Reactive oxygen species and cell signaling - Respiratory burst in macrophage signaling
Reactive oxygen species and cell signaling - Respiratory burst in macrophage signaling
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DOI：
10.1164/rccm.2206007
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发表时间：
2002-12-15
影响因子：
24.7
通讯作者：
Torres, M
中科院分区：
文献类型：
--
作者：
Forman, HJ;Torres, M
吞噬细胞如嗜中性粒细胞和巨噬细胞在吞噬作用或用多种试剂刺激期间通过活化烟酰胺腺嘌呤二核苷酸磷酸还原（NADPH）氧化酶产生活性氧物质（ROS），所述NADPH氧化酶由驻留质膜和胞质蛋白组分组装在质膜处。吞噬细胞NADPH氧化酶的一个亚基现在被认为是存在于吞噬细胞以外的细胞中的NADPH氧化酶或NOX家族的成员。ROS的生理产生涉及从转录激活到细胞增殖和凋亡的各种生理反应。由NADPH氧化酶刺激引起的超氧化物和过氧化氢（H2O2）的增加是短暂的，部分原因是抗氧化酶的存在，其将其浓度恢复到刺激前的稳态水平。因此，抗氧化酶可能在ROS信号转导的“关闭”阶段起作用。在其短暂的升高，H2O2可以作为一个关键的信号酶的修饰剂，通过可逆氧化的关键硫醇。巯基与H2O2在其未质子化状态下的快速反应将为生理细胞信号传导所必需的特异性提供潜在机制。
Phagocytes such as neutrophils and macrophages produce reactive oxygen species (ROS) during phagocytosis or stimulation with a wide variety of agents through activation of nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase that is assembled at the plasma membrane from resident plasma membrane and cytosolic protein components. One of the subunits of the phagocyte NADPH oxidase is now recognized as a member of a family of NADPH oxidases, or NOX, present in cells other than phagocytes. Physiologic generation of ROS has been implicated in a variety of physiologic responses from transcriptional activation to cell proliferation an apoptosis. The increase in superoxide and hydrogen peroxide (H2O2) that results from stimulation of the NADPH oxidase Is transient, in part due to the presence of the antioxidant enzymes, which return their concentrations to the prestimulation steady state level. Thus, the antioxidant enzymes may function in the "turn-off" phase of signal transduction by ROS. During its transient elevation, H2O2 may act as a modifier of key signaling enzymes through reversible oxidation of critical thiols. The rapid reaction of thiols with H2O2 when in their unprotonated state would provide a potential mechanism for the specificity that is necessary for physiologic cell signaling.