The toxicity of 6-hydroxydopamine on PC12 and P19 cells

Considerable evidence implicates the involvement of mitochondrial dysfuncti on in neurodegenerative diseases. 60HDA is a mitochondrial complex I inhibi tor which is frequently used to model Parkinson's disease-like cell loss. W e investigated the cell death pathways triggered by 60HDA in PC12 and P19 c ells with a view to shedding light on the molecular basis of Parkinson's di sease. We found that 60HDA triggered mostly necrosis and less than 5% apopt osis in PC12 cells, whereas 60HDA-induced death in P19 cells was apoptotic. While desipramine, a dopamine uptake blocker, attenuated 60HDA-induced apo ptosis in PC12 cells, this compound had no effect on the large scale necrot ic death. Furthermore, desipramine failed to reduce apoptosis in 60HDA-trea ted P19 cells, suggesting that the mechanism of 60HDA toxicity does not req uire uptake via the dopamine transporter. As cell death triggered by 60HDA was not blocked by free radical scavengers or NMDA receptor antagonists, a non-specific extracellular mechanism may be involved. (C) 1999 Elsevier Sci ence B.V. All rights reserved.