title: Redox modulation of the response of NADH oxidase activity of rat liver plasma membranes to cyclic AMP plus ATP.
abstract: NADH oxidase activity of rat liver plasma membranes was inhibited by low concentrations (1-100 nM) of ATP. The inhibition was amplified by addition of nanomolar concentrations (0.1-10) of cyclic AMP. The inhibition was complex and related to a marked increase in the Km for NADH at high NADH concentrations together with a concomitant decrease in the Vmax. In the absence of added or residual ATP, cyclic AMP was without effect. The response of cyclic AMP + ATP was inhibited by low concentrations of the selective inhibitor of cyclic AMP-dependent protein kinase, H-89 but not by staurosporin. The Vmax but not the Km was modified by treating the plasma membranes with a mild oxidizing agent, N-chlorosuccinamide, or with the reducing agent, dithiothreitol. In the presence of dithiothreitol, the Vmax was reduced by cyclic AMP + ATP. In contrast, in the presence of N-chlorosuccinamide, the Vmax was increased by cyclic AMP + ATP relative to cyclic AMP + ATP alone. Thus, the effect of cyclic AMP + ATP on the Vmax could be either an increase or a decrease depending on whether the membranes were oxidized or reduced. The results demonstrate regulation of NADH oxidase activity of rat liver plasma membranes through cyclic AMP-mediated phosphorylation by membrane-located protein kinase activities where the final response is dependent on the oxidation-reduction status of the plasma membranes.
authors.affiliation: Department of Medicinal Chemistry, Purdue University West Lafayette, Indiana 47907, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Morré
authors.forename: J C
authors.initials: JC
authors.lastname: Rodriguez-Aguilera
authors.forename: P
authors.initials: P
authors.lastname: Navas
authors.forename: D M
authors.initials: DM
authors.lastname: Morre
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology*; D000242:Cyclic AMP / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000187:drug effects*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000187:drug effects*; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D047428:Protein Kinase Inhibitors; D051381:Rats; D019163:Reducing Agents / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D013449:Sulfonamides
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D009097:Multienzyme Complexes; D016877:Oxidants; D047428:Protein Kinase Inhibitors; D019163:Reducing Agents; D013449:Sulfonamides; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D019311:Staurosporine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D004229:Dithiothreitol