Rotenone and MPP+ preferentially redistribute apoptosis-inducing factor in apoptotic dopamine neurons.
Rotenone and 1-methyl-4-phenylpyridinium produce parkinsonian models and we determined whether their mitochondrially mediated actions differentially redistributed the apoptogenic proteins, apoptosis-inducing factor and cytochrome c. Cultured rat mesencephalic dopamine neurons were exposed to rotenone (30 nM) and 1-methyl-4-phenylpyridinium (300 muM, 24 and 48 h) and apoptosis and mitochondrial redistribution of cytochrome c or apoptosis-inducing factor were quantified. Tyrosine hydroxylase-positive dopamine neurons underwent apoptosis (shrinkage, less neurites) and 40% released apoptosis-inducing factor with rotenone (24 h), whereas cytochrome c release reached this value at 48 h when 70% of cells had released apoptosis-inducing factor-positive. 1-Methyl-4-phenylpyridinium produced similar redistribution patterns for both proteins. Preferential redistribution of apoptosis-inducing factor before cytochrome c in dopamine neurons indicates caspase-independent mitochondrial proapoptotic signalling predominates in these parkinsonian models.
Lim
Maria L R
ML
Department of Biochemistry and Molecular Biology, Monash University, Australia.
Mercer
Linda D
LD
Nagley
Phillip
P
Beart
Philip M
PM
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004622:Embryo, Mammalian; D006540:Herbicides / Q000494:pharmacology*; D008636:Mesencephalon / Q000166:cytology; D008928:Mitochondria / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D051033:Apoptosis Inducing Factor; D006540:Herbicides; D012402:Rotenone; C028404:rotenolone; D045304:Cytochromes c; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine