Carbon monoxide, reactive oxygen signaling, and oxidative stress.
The ubiquitous gas, carbon monoxide (CO), is of substantial biological importance, but apart from its affinity for reduced transition metals, particularly heme-iron, it is surprisingly nonreactive-as is the ferrous-carbonyl-in living systems. CO does form strong complexes with heme proteins for which molecular O2 is the preferred ligand and to which are attributed diverse physiological, adaptive, and toxic effects. Lately, it has become apparent that both exogenous and endogenous CO produced by heme oxygenase engender a prooxidant milieu in aerobic mammalian cells which initiates signaling related to reactive oxygen species (ROS) generation. ROS signaling contingent on CO can be segregated by CO concentration-time effects on cellular function, by the location of heme proteins, e.g., mitochondrial or nonmitochondrial sites, or by specific oxidation-reduction (redox) reactions. The fundamental responses to CO involve overt physiological regulatory events, such as activation of redox-sensitive transcription factors or stress-activated kinases, which institute compensatory expression of antioxidant enzymes and other adaptations to oxidative stress. In contrast, responses originating from highly elevated or protracted CO exposures tend to be nonspecific, produce untoward biological oxidations, and interfere with homeostasis. This brief overview provides a conceptual framework for understanding CO biology in terms of this physiological-pathological hierarchy.
Piantadosi
Claude A
CA
Department of Medicine, Duke University Medical Center, Box 3315 CR II Building White Zone, Trent Drive, Durham, NC 27710, USA. piant001@mc.duke.edu
D000220:Adaptation, Biological; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D006420:Hemeproteins / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
D006420:Hemeproteins; D017382:Reactive Oxygen Species; D002248:Carbon Monoxide