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  • Title: Rotenone and MPP+ preferentially redistribute apoptosis-inducing factor in apoptotic dopamine neurons.
    Author: Lim ML, Mercer LD, Nagley P, Beart PM.
    Journal: Neuroreport; 2007 Mar 05; 18(4):307-12. PubMed ID: 17435593.
    Abstract:
    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.
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