title: In vitro inhibition of topoisomerase IIα by reduced glutathione.
abstract: In most cells, the major intracellular redox buffer is glutathione (GSH) and its disulfide-oxidized (GSSG) form. The GSH/GSSG system maintains the intracellular redox balance and the essential thiol status of proteins by thiol disulfide exchange. Topoisomerases are thiol proteins and are a target of thiol-reactive substances. In this study, the inhibitory effect of physiological concentration of GSH and GSSG on topoisomerase IIα activity in vitro was investigated. GSH (0-10 mM) inhibited topoisomerase IIα in a concentration-dependent manner while GSSG (1-100 µM) had no significant effect. These findings suggest that the GSH/GSSG system could have a potential in vivo role in regulating topoisomerase IIα activity.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Zahid M
authors.initials: ZM
authors.lastname: Delwar
authors.forename: Marina Fernanda
authors.initials: MF
authors.lastname: Vita
authors.forename: Åke
authors.initials: Å
authors.lastname: Siden
authors.forename: Mabel
authors.initials: M
authors.lastname: Cruz
authors.forename: Juan Sebastian
authors.initials: JS
authors.lastname: Yakisich
mesh_terms: D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D057075:Enzyme Assays; D005978:Glutathione / Q000737:chemistry*; D006801:Humans; D010084:Oxidation-Reduction; D059005:Topoisomerase II Inhibitors / Q000737:chemistry*
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II; D005978:Glutathione