Unlike MPP+, apoptosis induced by 6-OHDA in PC12 cells is independent of mitochondrial inhibition.
The mechanisms of 6-hydroxydopamine (6-OHDA) cytotoxicity were studied in vitro using the PC12 cell line. Following a 24 h exposure, this neurotoxin induced apoptosis and a dose-dependent decrease in cell survival. The presence of monoamine oxidase inhibitors, tranylcypromine and clorgyline, together with 6-OHDA had neither synergistic nor protective effects. Unlike 1-methyl-4-phenylpyridinium (MPP+), 6-OHDA toxicity to PC12 cells remained unchanged when glycolysis was prevented by either depleting glucose from the culture medium or growing the cells in low-glucose medium containing 2-deoxy-glucose. These results suggest that the inhibition of mitochondrial respiration is not responsible for the cell death induced by 6-OHDA.
Wu
Y
Y
INSERM U318, CHU Michallon, Grenoble, France.
Blum
D
D
Nissou
M F
MF
Benabid
A L
AL
Verna
J M
JM
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003010:Clorgyline / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D016627:Oxidopamine / Q000633:toxicity*; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D014191:Tranylcypromine / Q000494:pharmacology
D018663:Adrenergic Agents; D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D014191:Tranylcypromine; D016627:Oxidopamine; D003010:Clorgyline; D015655:1-Methyl-4-phenylpyridinium