Glutathione protects PC12 cells from ascorbate- and dopamine-induced apoptosis.
The role of reduced glutathione (GSH) on ascorbate- and dopamine-induced apoptosis in PC12 cells was investigated. Ascorbate is a potent reducing agent and is thus expected to protect against dopamine-induced apoptosis. However, we found that both ascorbate and dopamine killed PC12 cells and ascorbate enhanced dopamine-induced toxicity. The EC50 of cell toxicity induced by ascorbate, dopamine and dopamine plus 0.1 mM ascorbate during 24-h treatment were 0.93+/-0.15 mM, 0.18+/-0.05 mM and 0.13+/-0.04 mM, respectively. When the medium contained 10 mM GSH, the EC50 increased approximately three- and sevenfold for ascorbate and dopamine, respectively. With increased treatment duration, no further toxic effects of ascorbate or dopamine were observed. The GSH synthesis inhibitor, DL-buthionine-(S,R)-sulfoximine (BSO), induced cell toxicity and potentiated the toxic effects of ascorbate and dopamine, suggesting that endogenous GSH participates in protecting against basal oxidative stress. We conclude that both ascorbate and dopamine induce apoptosis in PC12 cells and further that GSH protects them from apoptosis. This study indicates that the toxic effects of ascorbate are potentially due to an oxidative mechanism, similar to that induced by dopamine.
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Department of Physiology, Queen's University, Kingston, Ontario, Canada. shins@post.queensu.ca
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D004298:Dopamine / Q000633:toxicity*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005978:Glutathione / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats
D018492:Dopamine Antagonists; D019328:Buthionine Sulfoximine; D005978:Glutathione; D001205:Ascorbic Acid; D004298:Dopamine