Selimi F, Campana A, Weitzman J, Vogel M W, Mariani J
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.
C R Acad Sci III. 2000 Nov;323(11):967-73. doi: 10.1016/s0764-4469(00)01243-9.
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.
杂合型Lurcher（Grid2Lc/+）小鼠的浦肯野细胞固有死亡伴随着颗粒细胞和橄榄核神经元的靶相关死亡。在Grid2Lc/+浦肯野细胞中，前半胱天冬酶-3的表达增加，并且在所有三种细胞类型死亡之前都检测到活化的半胱天冬酶-3。Grid2Lc/+突变体中Bax失活可挽救颗粒细胞，但不能挽救浦肯野细胞。在这里，我们表明，虽然Bax失活抑制了两种细胞类型中的半胱天冬酶-3活化，但p53失活并不影响Grid2Lc/+小鼠中的半胱天冬酶-3活化和神经元丢失。Grid2Lc/+浦肯野细胞中前半胱天冬酶-3的上调独立于Bax和p53。这些结果表明，Grid2Lc/+颗粒细胞死亡依赖于Bax和半胱天冬酶-3活化，而几种途径可以介导Grid2Lc/+浦肯野细胞死亡。
