title: Arachidonic acid converts the glutathione depletion-induced apoptosis to necrosis by promoting lipid peroxidation and reducing caspase-3 activity in rat glioma cells.
abstract: Intracellular glutathione (GSH) depletion induced by buthionine sulfoximine (BSO) caused cell death that seemed to be apoptosis in C6 rat glioma cells. Arachidonic acid (AA) promoted BSO-induced cell death by accumulating reactive oxygen species (ROS) or hydroperoxides. AA inhibited caspase-3 activation and internucleosomal DNA fragmentation during the BSO-induced GSH depletion. Furthermore, AA reduced intracellular ATP content, induced dysfunction of mitochondrial membrane and enhanced 8-hydroxy-2'-deoxyguanosine (8-OH-dG) production. There was significant increase of 12-lipoxygenase activity in the presence of AA under the BSO-induced GSH depletion in C6 cells. These results suggest that AA promotes cell death by changing to necrosis from apoptosis through lipid peroxidation initiated by lipid hydroperoxides produced by 12-lipoxygenase under the GSH depletion in C6 cells. Some ROS such as hydroperoxide produced by unknown pathway make hydroxy radicals and induce 8-OH-dG formation in the cells. The conversion of apoptosis to necrosis may be a possible event under GSH depleted conditions.
authors.affiliation: Department of Molecular Pharmacology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan. higuchiy@med.kanazawa-u.ac.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Higuchi
authors.forename: Tanihiro
authors.initials: T
authors.lastname: Yoshimoto
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004789:Enzyme Activation; D005910:Glioma / Q000201:enzymology* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008564:Membrane Potentials; D009336:Necrosis; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; D000255:Adenosine Triphosphate; D001092:Arachidonate 12-Lipoxygenase; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; D010100:Oxygen