Role of oxidants in the signaling pathway of preconditioning.
This review focuses on the possible role of reactive oxygen species in the pathogenesis of this phenomenon. Evidence in support of a role of oxidants in preconditioning has come from the observation that administration of oxygen radical scavengers during the reperfusion period following the initial "preconditioning" ischemia could prevent the phenomenon. In addition, a brief exposure to a low, nontoxic dose of oxygen radicals may reproduce the beneficial effects of ischemic preconditioning, thus suggesting that radicals can directly trigger the preconditioning pathway. To explain the effects of oxidants in this setting, it has been suggested that reperfusion after the initial, "preconditioning" ischemic episode results in the generation of relatively low amounts of oxygen radicals, which are insufficient to determine cell necrosis, but nevertheless could modify cellular activities that have been implicated as mediators of the preconditioning phenomenon. Recent evidence suggests that low levels of oxidants may have a modulatory role on several cell functions. Possible mechanisms of oxidant-mediated protection might be protein kinase C and other kinases, ATP-dependent potassium channels, or changes in sulfhydryl group redox state, while an effect on adenosine metabolism, or the induction of myocardial stunning presumably does not contribute to oxidant-mediated preconditioning. Finally, de novo protein synthesis and gene expression, and increased antioxidant defenses might be involved in the late phase of preconditioning. In summary, available data strongly suggest that oxygen radicals might be possible mediators of preconditioning. However, further investigation is required to clearly elucidate their exact role and mechanisms of action.
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Division of Cardiology, University of Perugia School of Medicine, Perugia, Italy.
Ambrosio
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D000818:Animals; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D017682:Myocardial Stunning / Q000378:metabolism; D016877:Oxidants / Q000502:physiology*; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism
D016877:Oxidants; D017382:Reactive Oxygen Species; D013481:Superoxides