Programmed cell death induced by glutathione depletion in PC 12 cells is blocked by inhibitors of 12 lipoxygenase, but does not appear to be mediated through the formation of 12 HETE derivatives.
Lipoxygenase metabolites have been postulated to be involved in the degenerative events provoked by oxidative stress in neuronal and nonneuronal targets, but their roles remain controversial. In the present work, we investigated the putative role of 12 lipoxygenase metabolites in the programmed cell death induced by glutathione depletion in PC 12 cells. Determinations of 12 lipoxygenase expression and activity reveal the presence of the enzyme in PC 12 cells, but the formation of arachidonate metabolites appears rather low and is not influenced by glutathione depletion. In addition, although the death induced by buthionine sulfoximine (BSO) treatment is abolished by known inhibitors of lipoxygenase enzymes, dexamethasone, a potent steroidal inhibitor of both cyclooxygenase and lipoxygenase pathways, fails to protect the cells from BSO-induced degeneration. Finally, incubation of the cells for 24 h in the presence of exogenous 12 HETE did not induce any significant decrease in cell viability. Our results indicate that 12 lipoxygenase is unlikely to play a major role in the process of cell degeneration provoked by glutathione depletion.
Université de Caen, CNRS-UMR 6551, Caen, France.
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D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000172:deficiency*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D016716:PC12 Cells / Q000166:cytology*; D051381:Rats
D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D019328:Buthionine Sulfoximine; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001092:Arachidonate 12-Lipoxygenase; D005978:Glutathione