Bax and p53 are differentially involved in the regulation of caspase-3 expression and activation during neurodegeneration in Lurcher mice |
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| Authors: | Selimi F Campana A Weitzman J Vogel M W Mariani J |
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| Institution: | 1. Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA;2. Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel;1. Institute of Medical Microbiology and Hygiene, Ulm University Hospital, Ulm, Germany;2. Department of Clinical Chemistry, Ulm University Hospital, Ulm, Germany;3. Central Facility for Electron Microscopy, Ulm University, Ulm, Germany |
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| 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. |
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