title: Inhibition of glutathione reductase by isoproterenol oxidation products.
abstract: Oxidative stress induced by catecholamines is a well recognized toxic event. This effect has been extensively observed in the heart, where high levels of catecholamines cause enzyme inhibition, lipid peroxidation, energy depletion and myocardial necrosis. Catecholamines can be converted into o-quinones and undergo cyclization into aminochromes. This process can occur enzymatically or through autoxidation and involves the formation of free radicals. Aminochromes are highly reactive molecules that can cause oxidation of protein sulfhydryl groups and deamination catalysis, among other deleterious effects; in addition, inhibition of some enzymes has been also reported. We have studied the effects of isoproterenol oxidation products (IOP) on glutathione reductase (GR) activity in vitro. Isoproterenol (ISO) autoxidation was conducted at 37 degrees C in the dark, for 4 h at pH 7.0 and this process was monitored by UV spectrophotometry at both 340 and 490nm. Addition of the autoxidized solution to GR in the presence of oxidized glutathione (GSSG) and NADPH showed that IOP inhibits GR in a competitive mode and that this effect increases during the 4 h incubation period. This inhibitory effect of IOP was partially prevented by the addition of reduced glutathione (GSH), L-cysteine and ascorbic acid to the reaction mixtures.
authors.affiliation: ICETA/CEQUP, Toxicology Department, Faculty of Pharmacy, Porto, Portugal. remiao@mail.ff.up.pt
authors.forename: F
authors.initials: F
authors.lastname: Remião
authors.forename: H
authors.initials: H
authors.lastname: Carmo
authors.forename: F D
authors.initials: FD
authors.lastname: Carvalho
authors.forename: M L
authors.initials: ML
authors.lastname: Bastos
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D019803:Glutathione Disulfide / Q000378:metabolism; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors*; D007202:Indicators and Reagents; D007545:Isoproterenol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000975:Antioxidants; D007202:Indicators and Reagents; D005980:Glutathione Reductase; D005978:Glutathione; D003545:Cysteine; D007545:Isoproterenol; D001205:Ascorbic Acid; D019803:Glutathione Disulfide