Extracellular toxicity of 6-hydroxydopamine on PC12 cells.
6-hydroxydopamine (6-OHDA) is usually thought to cross cell membrane through dopamine uptake transporters, to inhibit mitochondrial respiration and to generate intracellular reactive oxygen species. In this study, we show that the anti-oxidants catalase, glutathione and N-acetyl-cysteine are able to reverse the toxic effects of 6-OHDA. These two latter compounds considerably slow down 6-OHDA oxidation in a cell free system suggesting a direct chemical interaction with the neurotoxin. Moreover, desipramine does not protect PC12 cells and 6-OHDA is also strongly toxic towards non-catecholaminergic C6 and NIH3T3 cells. These results thus suggest that 6-OHDA toxicity on PC12 cells mainly involves an extracellular process.
Blum
D
D
ULB-Campus Erasme, Laboratory of Neurophysiology, Department of Neurosciences, 808 Rte de Lennik, CP601, 1070, Brussels, Belgium. david.blum@ulb.ac.be
Torch
S
S
Nissou
M F
MF
Benabid
A L
AL
Verna
J M
JM
D016475:3T3 Cells; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009498:Neurotoxins / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity*; D016716:PC12 Cells / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000502:physiology
D009498:Neurotoxins; D017382:Reactive Oxygen Species; D016627:Oxidopamine