Mechanisms of cell death in oxidative stress.
Reactive oxygen or nitrogen species (ROS/RNS) generated endogenously or in response to environmental stress have long been implicated in tissue injury in the context of a variety of disease states. ROS/RNS can cause cell death by nonphysiological (necrotic) or regulated pathways (apoptotic). The mechanisms by which ROS/RNS cause or regulate apoptosis typically include receptor activation, caspase activation, Bcl-2 family proteins, and mitochondrial dysfunction. Various protein kinase activities, including mitogen-activated protein kinases, protein kinases-B/C, inhibitor-of-I-kappaB kinases, and their corresponding phosphatases modulate the apoptotic program depending on cellular context. Recently, lipid-derived mediators have emerged as potential intermediates in the apoptosis pathway triggered by oxidants. Cell death mechanisms have been studied across a broad spectrum of models of oxidative stress, including H2O2, nitric oxide and derivatives, endotoxin-induced inflammation, photodynamic therapy, ultraviolet-A and ionizing radiations, and cigarette smoke. Additionally ROS generated in the lung and other organs as the result of high oxygen therapy or ischemia/reperfusion can stimulate cell death pathways associated with tissue damage. Cells have evolved numerous survival pathways to counter proapoptotic stimuli, which include activation of stress-related protein responses. Among these, the heme oxygenase-1/carbon monoxide system has emerged as a major intracellular antiapoptotic mechanism.
Ryter
Stefan W
SW
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. Ryters@upmc.edu
Kim
Hong Pyo
HP
Hoetzel
Alexander
A
Park
Jeong W
JW
Nakahira
Kiichi
K
Wang
Xue
X
Choi
Augustine M K
AM
D000818:Animals; D017209:Apoptosis; D002248:Carbon Monoxide / Q000378:metabolism / Q000502:physiology; D016923:Cell Death; D051547:Heme Oxygenase-1 / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D018384:Oxidative Stress; D010778:Photochemotherapy; D011827:Radiation; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1