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Mediation of Signal Transduction by Oxidants

Michael S. Wolin, Kamal M. Mohazzab-H.


Signaling mechanisms involving reactive O2 species (ROS) are being investigated for their roles in processes as diverse as the control of vascular tone, carotid body function, thrombosis, and proliferation, in response to stimuli such as changes in O2 levels, inflammation, ischemia/reperfusion, and receptor function. It appears that specific ROS whose levels change in response to physiological stimuli interact with control mechanisms present in cells, permitting these species to function within cells in a second-messenger-like manner and in cell-to-cell tissue hormone-type signaling. In this chapter, we present many of the better-documented oxidant interactions observed in mammalian cells and tissues. We focus on processes that are involved in acute second-messenger-like signaling events and mechanisms that control the production of these species.

The concentrations of individual ROS formed by cells and tissues are usually tightly controlled by specific metabolizing and scavenging systems that exist for each species, because an excessive production usually results in cytotoxic effects. Thus, interactions of individual oxidant species with cell-control mechanisms that occur in the absence of cytotoxic effects are potentially involved in signaling processes. Certain signaling systems are very sensitive to low levels of species including superoxide anion (O2•−) and hydrogen peroxide (H2O2) normally produced by cells, and these mechanisms are likely to participate in physiological regulation. As summarized in Figure 1, the signaling systems that are very sensitive oxidants generally appear to be linked to the function of the metabolic pathways that exist for these species. In...

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