Extracellular toxicity of 6-hydroxydopamine on PC12 cells

6-hydroxydopamine (6-OHDA) is usually thought to cross cell membrane throug h dopamine uptake transporters, to inhibit mitochondrial respiration and to generate intracellular reactive oxygen species. In this study, we show tha t the anti-oxidants catalase, glutathion and N-acetyl-cystein are able to r everse the toxic effects of 6-OHDA. These two latter compounds considerably slow down 6-OHDA oxidation in a cell free system suggesting a direct chemi cal interaction with the neurotoxin. Moreover, desipramine does not protect PC12 cells and 6-OHDA is also strongly toxic towards noncatecholaminergic C6 and NIH3T3 cells. These results thus suggest that 6-OHDA toxicity on PC1 2 cells mainly involves an extracellular process. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.