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 μM, 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.

[1]  K. Heidenreich,et al.  The pesticide rotenone induces caspase‐3‐mediated apoptosis in ventral mesencephalic dopaminergic neurons , 2003, Journal of neurochemistry.

[2]  A. H. V. Schapira,et al.  MITOCHONDRIAL COMPLEX I DEFICIENCY IN PARKINSON'S DISEASE , 1989, The Lancet.

[3]  D. Nicholls,et al.  Calpain I Induces Cleavage and Release of Apoptosis-inducing Factor from Isolated Mitochondria* , 2005, Journal of Biological Chemistry.

[4]  W. Dauer,et al.  Parkinson's Disease Mechanisms and Models , 2003, Neuron.

[5]  G. Kroemer,et al.  Apoptosis-inducing factor (AIF): caspase-independent after all , 2004, Cell Death and Differentiation.

[6]  T. Sherer,et al.  The rotenone model of Parkinson's disease: genes, environment and mitochondria. , 2003, Parkinsonism & related disorders.

[7]  P. Nicotera,et al.  1-Methyl-4-phenylpyridinium induces autocrine excitotoxicity, protease activation, and neuronal apoptosis. , 1998, Molecular pharmacology.

[8]  G. Fiskum,et al.  Mitochondrial Mechanisms of Neural Cell Death and Neuroprotective Interventions in Parkinson's Disease , 2003, Annals of the New York Academy of Sciences.

[9]  J. Dichgans,et al.  Protection by Synergistic Effects of Adenovirus-Mediated X-Chromosome-Linked Inhibitor of Apoptosis and Glial Cell Line-Derived Neurotrophic Factor Gene Transfer in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Model of Parkinson's Disease , 2000, The Journal of Neuroscience.

[10]  Baohong Chen,et al.  Relative timing of redistribution of cytochrome c and Smac/DIABLO from mitochondria during apoptosis assessed by double immunocytochemistry on mammalian cells. , 2006, Experimental cell research.

[11]  J. Bilsland,et al.  Caspase Inhibitors Attenuate 1-Methyl-4-Phenylpyridinium Toxicity in Primary Cultures of Mesencephalic Dopaminergic Neurons , 2002, The Journal of Neuroscience.

[12]  Todd B. Sherer,et al.  Chronic systemic pesticide exposure reproduces features of Parkinson's disease , 2000, Nature Neuroscience.

[13]  Jun Chen,et al.  Apoptosis inducing factor mediates caspase‐independent 1‐methyl‐4‐phenylpyridinium toxicity in dopaminergic cells , 2005, Journal of neurochemistry.

[14]  Robert M. Silva,et al.  CHOP/GADD153 is a mediator of apoptotic death in substantia nigra dopamine neurons in an in vivo neurotoxin model of parkinsonism , 2005, Journal of neurochemistry.

[15]  E. Schon,et al.  Neuronal degeneration and mitochondrial dysfunction. , 2003, The Journal of clinical investigation.

[16]  Keith Hyland,et al.  Distinct Mechanisms of Neurodegeneration Induced by Chronic Complex I Inhibition in Dopaminergic and Non-dopaminergic Cells* , 2004, Journal of Biological Chemistry.

[17]  Y. Oh,et al.  Caspase-Dependent and -Independent Cell Death Pathways in Primary Cultures of Mesencephalic Dopaminergic Neurons after Neurotoxin Treatment , 2003, The Journal of Neuroscience.

[18]  P. Nicotera,et al.  Energy Requirement for Caspase Activation and Neuronal Cell Death , 2000, Brain pathology.

[19]  S. Korsmeyer,et al.  Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[20]  V. Dawson,et al.  Role of AIF in caspase-dependent and caspase-independent cell death , 2004, Oncogene.

[21]  Malcolm K Horne,et al.  Dietary polyphenols protect dopamine neurons from oxidative insults and apoptosis: investigations in primary rat mesencephalic cultures. , 2005, Biochemical pharmacology.

[22]  T. Sherer,et al.  Mechanistic Approaches to Parkinson's Disease Pathogenesis , 2002, Brain pathology.

[23]  T. Dawson,et al.  Molecular Pathways of Neurodegeneration in Parkinson's Disease , 2003, Science.

[24]  G. Fiskum,et al.  Mitochondrial mechanisms of neural cell apoptosis , 2004, Journal of neurochemistry.