title: Polyunsaturated fatty acids promote 8-hydroxy-2-deoxyguanosine formation through lipid peroxidation under the glutamate-induced GSH depletion in rat glioma cells.
abstract: It has been reported that glutamate decreased the intracellular glutathione (GSH) concentration and thereby induced cell death in C6 rat glioma cells. Polyunsaturated fatty acids such as arachidonic acid, gamma-linolenic acid, and linoleic acid enhanced lipid peroxidation promoting 8-hydroxy-2'-deoxyguanosine (8-OH-dG) formation under the glutamate-induced GSH-depletion. The enhancement of lipid peroxidation by polyunsaturated fatty acids was species-dependent. Some antioxidants capable of scavenging oxygen and lipid radicals and some iron or copper scavengers inhibited both the lipid peroxidation and the 8-OH-dG formation, consequently protecting against cell death induced by glutamate-induced GSH depletion. These results suggest that GSH depletion caused by glutamate induces lipid peroxidation and consequently 8-OH-dG formation and that polyunsaturated fatty acids enhance lipid peroxidation associated with mediated 8-OH-dG formation through a chain reaction.
authors.affiliation: Department of Pharmacology, Kanazawa University School of Medicine, Kanazawa 920-8640, Japan. higuchiy@med.kanazawa-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Higuchi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D000975:Antioxidants; D002614:Chelating Agents; D005231:Fatty Acids, Unsaturated; D018698:Glutamic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005978:Glutathione