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1 Biodynamics Institute, Louisiana State University, Baton Rouge, Louisiana, United States
2 Chemistry and Biochemisty, University of California, Los Angeles, Los Angeles, California, United States
3 Pharmacology, University of California, Los Angeles, California, United States
4 Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States
5 (6) Ethel Percy Andrus Gerontology Center and Division of Molecular & Computational Biology, University of Southern California, Los Angeles, California, United States
* To whom correspondence should be addressed. E-mail: wpryor{at}lsu.edu.
We review gases that can affect oxidative stress and that themselves may be radicals. We discuss O2 toxicity, invoking superoxide, hydrogen peroxide, and the hydroxyl radical. We also discuss superoxide dismutase (SOD) and both ground-state, triplet oxygen (3O2), and the more energetic, reactive singlet oxygen (1O2). Nitric oxide (.NO) is a free radical with cell signaling functions. Besides its role as a vasorelaxant, .NO and related species have other functions. Other endogenously-produced gases include carbon monoxide (CO), carbon dioxide (CO2), and hydrogen sulfide (H2S). Like .NO, these species impact free radical biochemistry. The coordinated regulation of these species suggests that they all are used in cell signaling. Nitric oxide, nitrogen dioxide, and the carbonate radical (CO3.- ) react selectively at moderate rates with non-radicals, but react fast with a second radical. These reactions establish "cross-talk" between reactive oxygen (ROS) and reactive nitrogen species (RNS). Some of these species can react to produce nitrated proteins and nitro-lipids. It has been suggested that ozone is formed in vivo. However, the biomarkers that were used to probe for ozone reactions may be formed by non-ozone-dependent reactions. We discuss this fascinating problem in the section on ozone. Very low levels of ROS or RNS may be mitogenic, but very high levels cause an oxidative stress that can result in growth arrest (transient or permanent), apoptosis, or necrosis. Between these extremes, many of the gasses discussed in this review will induce transient adaptive responses in gene expression that enable cells and tissues to survive. Such adaptive mechanisms are thought to be of evolutionary importance.
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