title: Compounds that induce isoforms of glutathione S-transferase with properties of a critical enzyme in defense against oxidative stress.
abstract: Compounds that upregulate enzymes that play critical roles in protection against free radical damage might be useful in treating diseases in which free radicals are pathological. To identify critical enzymes and their upregulators, compounds that were not free radical scavengers were screened for the ability to increase the IC(50) of the human neuronal cell line IMR-32 for hydrogen peroxide. Subsequently, enzymes upregulated by compounds that increased the IC(50) were identified. All of the compounds identified that increased the IC(50) also increased the specific activity of glutathione S-transferase (GST). In addition, compound-caused increases in the specific activity of GST correlated with compound-caused increases in the IC(50), the expected behaviour if GST was a critical enzyme. The GST isoform composition changed on upregulation, suggesting the upregulation of isoforms with anti-free radical activities. Structural features of compounds concurrently increasing the IC(50) and upregulating GST were identified.
authors.affiliation: National Research Council of Canada, Institute for Biological Sciences, Ottawa, Ontario, K1A 0R6, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Fiander
authors.forename: H
authors.initials: H
authors.lastname: Schneider
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D009474:Neurons; D018384:Oxidative Stress
chemical_list: D007527:Isoenzymes; D006861:Hydrogen Peroxide; D005982:Glutathione Transferase