Mechanisms of Cell Death in Oxidative Stress

Antioxid Redox Signal. 2007 Jan;9(1):49-89. doi: 10.1089/ars.2007.9.49.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

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

Substances

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