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Title: Compensatory caspase activation in MPP+-induced cell death in dopaminergic neurons
Authors: Chee, J.L.Y.
Guan, X.L.
Lee, J.Y. 
Dong, B.
Leong, S.M. 
Ong, E.H.
Liou, A.K.F.
Lim, T.M. 
Keywords: AIF
Cytochrome c
Dopaminergic neuron
Parkinson's disease
Issue Date: Jan-2005
Citation: Chee, J.L.Y., Guan, X.L., Lee, J.Y., Dong, B., Leong, S.M., Ong, E.H., Liou, A.K.F., Lim, T.M. (2005-01). Compensatory caspase activation in MPP+-induced cell death in dopaminergic neurons. Cellular and Molecular Life Sciences 62 (2) : 227-238. ScholarBank@NUS Repository.
Abstract: Many have hypothesized that cell death in Parkinson's disease is via apoptosis and, specifically, by the mitochondrial-mediated apoptotic pathway. We tested this hypothesis using a mouse dopaminergic cell line of mesencephalic origin, MN9D, challenged with the Parkinsonism-causing neurotoxin MPP + (1-methyl-4-phenylpyridinium ion). Apoptosis was the main mode of cell death when the cells were subjected to MPP+ treatment under serum-free conditions for 24 h. Caspase-3 and caspase-9, however, were not activated, thus indicating the existence of alternate or compensatory cell death pathway(s) in dopaminergic neuronal cells. Using caspase inhibitors, we demonstrated that these pathways involve caspase-2, -8, -6 and -7. A time-course study indicated that activation of caspase-2 and -8 occurred up-stream of caspase-6 and caspase-7. Upon MPP+ challenge, the apoptosis-inducing factor was translocated from the mitochondria into the MN9D cytosol and nucleus. These results suggest the existence of alternative apoptotic pathways in dopaminergic neurons.
Source Title: Cellular and Molecular Life Sciences
ISSN: 1420682X
DOI: 10.1007/s00018-004-4413-4
Appears in Collections:Staff Publications

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