Mechanisms of cell death in oxidative stress.

Abstract

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.

• Authors: Stefan W Ryter, Hong Pyo Kim, Alexander Hoetzel, Jeong W Park, Kiichi Nakahira, Xue Wang, Augustine M K Choi
• Journal: Antioxidants & redox signaling (Antioxid Redox Signal) Vol. 9 Issue 1 Pg. 49-89 (Jan 2007) ISSN: 1523-0864 [Print] United States
• PMID: 17115887 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Reactive Nitrogen Species
• Reactive Oxygen Species
• Carbon Monoxide
• Heme Oxygenase-1

Topics

• Animals
• Apoptosis
• Carbon Monoxide (metabolism, physiology)
• Cell Death
• Heme Oxygenase-1 (metabolism, physiology)
• Humans
• Models, Biological
• Oxidative Stress
• Photochemotherapy
• Radiation
• Reactive Nitrogen Species (metabolism)
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (metabolism)