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Persad S, Rupp H, Jindal R, Arneja J, Dhalla NS: Modification of cardiac beta-adrenoceptor mechanisms by H2O2. Am J Physiol. 1998 Feb;274(2 Pt 2):H416-23.
From the role of oxidative stress in cardiac dysfunction, we investigated the effect of H2O2, an activated species of oxygen, on beta-adrenoceptors, G proteins, and adenylyl cyclase activities. Rat heart membranes were incubated with different concentrations of H2O2 before the biochemical parameters were measured. Both the affinity and density of beta 1-adrenoceptors were decreased, whereas the density of the beta 2-adrenoceptors was decreased and the affinity was increased by 1 mM H2O2. Time- and concentration-dependent biphasic changes in adenylyl cyclase activities in the absence or presence of isoproterenol were observed when membranes were incubated with H2O2; however, activation of the enzyme by isoproterenol was increased or unaltered. The adenylyl cyclase activities in the absence or presence of forskolin, NaF, and Gpp (NH) p were depressed by H2O2. Catalase alone or in combination with mannitol was able to significantly decrease the magnitude of alterations due to H2O2. The cholera toxin-stimulated adenylyl cyclase activity and ADP ribose labeling of Gs proteins were decreased by treatment with 1 mM H2O2, whereas Gi protein activities, as reflected by pertussis toxin-stimulation of adenylyl cyclase and ADP ribosylation, were unaltered. The Gs and Gi protein immunoreactivities, estimated by labeling with respective antibodies, indicate a decrease in binding to the 45-kDa band of Gs protein, whereas no change in the binding of antibodies to the 52-kDa band of Gs protein or the 40-kDa subunit of Gi protein was evident when the membranes were treated with 1 mM H2O2. These results suggest that H2O2 in high concentrations may attenuate the beta-adrenoceptor-linked signal transduction in the heart by changing the functions of Gs proteins and the catalytic subunit of the adenylyl cyclase enzyme. |
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