Bax and p53 are differentially involved in the regulation of caspase-3 expression and activation during neurodegeneration in Lurcher mice.
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.
Selimi
F
F
Laboratoire Développement et vieillissement du système nerveux, Institut des neurosciences, CNRS-UMR7624, université Pierre-et-Marie-Curie, boîte 14, 9, quai Saint-Bernard, 75005 Paris, France. Fekrije.Selimi@snv.jussieu.fr
Campana
A
A
Weitzman
J
J
Vogel
M W
MW
Mariani
J
J
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D053148:Caspase 3; D020169:Caspases / Q000235:genetics* / Q000378:metabolism*; D003433:Crosses, Genetic; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D011689:Purkinje Cells / Q000473:pathology / Q000502:physiology; D017470:Receptors, Glutamate / Q000235:genetics / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017470:Receptors, Glutamate; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C107913:glutamate receptor delta 2; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases