ADENOSINE ACTS AS AN ENDOGENOUS ACTIVATOR OF THE CELLULAR ANTIOXIDANT DEFENSE SYSTEM

Oxygen free radicals have been implicated in the pathogenesis of ischemic cell injuries. These free radicals are normally scavenged by antioxidant enzymes. Adenosine is normally released during ischemia and protects against ischemic injuries by interacting with adenosine receptors (ARs). The mechanism underlying its cytoprotective action is unclear. In this report, we provide evidence that activation of a unique A,AR in rat basophilic leukemia cells (RBL-2H3) leads to a 2 to 3 fold increase in activity of superoxide dismutase, catalase and glutathione peroxidase and also increases in the activity of glutathione reductase. Similar increases in enzyme activity were elicited in bovine and human endothelial cells, rat cardiac myocytes and smooth muscle cells. Increases in enzyme activity were attenuated by theophylline (an antagonist of the A(3)AR) and by pertussis toxin, implicating a role of A(3)AR/G(i) protein in the activation. Importantly, activation of the A(3)AR decreased the degree of lipid peroxidation in these cells. These data provide strong evidence that the cytoprotective action of adenosine during ischemic cell injuries is mediated, at least in part, via a novel mechanism - activation of the cellular antioxidant enzymes. (C) 1994 Academie Press, Inc.