The effects of ascorbic acid on dopamine-induced death of PC12 cells are dependent on exposure kinetics.
The role of ascorbic acid on dopamine (DA) oxidation-mediated cytotoxicity was studied using the PC12 cell line. DA cytotoxicity was slightly attenuated by ascorbic acid, whereas the cytotoxicity of 6-hydroxydopamine (6-OHDA), a DA oxidation product, was markedly potentiated. To elucidate the relationship between the ascorbic acid effect and the degree of DA oxidation, ascorbic acid was added in a time-dependent fashion after DA treatment. We found greater cell death the later ascorbic acid was applied. Treatment of cells with glutathione alleviated DA- and 6-OHDA-induced cell death, while L-buthionine sulfoximine potentiated DA and 6-OHDA cytotoxicity. Ascorbic acid combined with glutathione eliminated the toxicity of DA and 6-OHDA. These results suggest that the interaction between DA and ascorbic acid is dependent upon the degree of DA oxidation and glutathione availability.
Choi
H Y
HY
Department of Physiology, Queen's University, Kingston, K7L 3N6, Ontario, Canada.
Song
J H
JH
Park
D K
DK
Ross
G M
GM
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D010599:Pharmacokinetics; D051381:Rats
D018696:Neuroprotective Agents; D009498:Neurotoxins; D019328:Buthionine Sulfoximine; D016627:Oxidopamine; D005978:Glutathione; D001205:Ascorbic Acid; D004298:Dopamine