Abstract
Intrinsic Purkinje cell death in heterozygous Lurcher (Grid2Lc/+) mice is accompanied by the target-related death of granule cells and olivary neurons. The expression of pro-caspase-3 is increased in Grid2Lc/+ Purkinje cells and activated caspase-3 is detected in all three cell types before their death. Bax inactivation in Grid2Lc/+ mutants rescues granule cells but not Purkinje cells. Here, we show that, while Bax inactivation inhibits caspase-3 activation in both cell types, p53 inactivation does not affect caspase-3 activation and neuronal loss in Grid2Lc/+ mice. The up-regulation of pro-caspase-3 in Grid2Lc/+ Purkinje cells is Bax and p53 independent. These results suggest that Grid2Lc/+ granule cell death is dependent on Bax and caspase-3 activation, whereas several pathways can mediate Grid2Lc/+ Purkinje cell death.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis
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Brain / pathology*
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Brain / physiopathology
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Caspase 3
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Caspases / genetics*
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Caspases / metabolism*
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Crosses, Genetic
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Gene Expression Regulation, Enzymologic
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Mice
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Mice, Knockout
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Mice, Neurologic Mutants
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Nerve Degeneration / genetics
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Nerve Degeneration / pathology
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Nerve Degeneration / physiopathology*
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Neurons / pathology
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Neurons / physiology*
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-bcl-2*
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Purkinje Cells / pathology
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Purkinje Cells / physiology
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Receptors, Glutamate / genetics
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Receptors, Glutamate / physiology
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Tumor Suppressor Protein p53 / deficiency
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / physiology*
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bcl-2-Associated X Protein
Substances
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Bax protein, mouse
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Glutamate
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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glutamate receptor delta 2
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Casp3 protein, mouse
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Caspase 3
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Caspases