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 attenuat ed by ascorbic acid, whereas the cytotoxicity of 6-hydroxydopamine (6-OHDA) , a DA oxidation product, was markedly potentiated. To elucidate the relati onship between the ascorbic acid effect and the degree of DA oxidation, asc orbic acid was added in a time-dependent fash ion after DA treatment. We fo und greater cell death the later ascorbic acid was applied. Treatment of ce lls with glutathione alleviated DA- and 6-OHDA-induced cell death, while L- buthionine sulfoximine potentiated DA and 6-OHDA cytotoxicity. Ascorbic aci d combined with glutathione eliminated the toxicity of DA and 6-OHDA. These results suggest that the interaction between DA and ascorbic acid is depen dent upon the degree of DA oxidation and glutathione availability. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.