cpp32 messenger RNA neosynthesis is induced by fatal axotomy and is not regulated by athanatal Bcl-2 over-expression

被引:20
作者
Guarin, E
Seuret, P
Nef, S
de Bilbao, F
Nef, P
Dubois-Dauphin, M
机构
[1] Univ Hosp Geneva, Dept Neuropsychiat, CH-1225 Geneva, Switzerland
[2] Ctr Med Univ Geneva, Dept Physiol, CH-1211 Geneva, Switzerland
[3] Univ Geneva, Dept Biochem, CH-1205 Geneva, Switzerland
关键词
apoptosis; axotomy; bax; Bcl-2; Cpp32; motoneurons;
D O I
10.1016/S0306-4522(98)00445-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In vivo, neuronal over-expression of the anti-apoptotic protein Bcl-2 prevents axotomy-induced motoneuron death and prolongs life in a mouse model of familial amyotrophic lateral sclerosis. The mechanism of these protective effects is still unknown. We have examined, in situ, the influence of Bcl-2 over-expression on the messenger RNA level of two pro-apoptotic, bax and cpp32, and one anti-apoptotic, bcl-xl, regulators of neuronal death. In neonates wild-type mice, cpp32 mRNA was increased in axotomized, dying motoneurons. No changes in bax and bcl-xl messenger RNAs expression were detected. A similar course was observed in protected axotomized neonate motoneurons of transgenic mice over-expressing Bcl-2. In adult wild-type mice no motoneuron death was detected one week after axotomy: bax and cpp32 messenger RNAs were increased and bcl-xl messenger RNA was decreased. Four weeks after the lesion, 60% of the lesioned facial motoneurons had disappeared. In the remaining motoneurons only cpp32 messenger RNA expression was superior to control level. In Bcl-2 transgenic mice, no axotomy-induced facial motoneurons death was detected but the course of the neosynthesis of cell death genes messenger RNAs was similar to wild-type mice. Bax, Bcl-x and CPP32 immunoreactivity were increased in facial motoneurons after axotomy. Thus, fatal axotomy induces cell death genes bax and cpp32 messenger RNAs neosynthesis which is not prevented by athanatal Bcl-2 over-expression. This suggests that the protective effect of Bcl-2 results from interactions with Bax and CPP32 at the post-translation lever without repercussion at the messenger RNA level. Axotomy induces cell death messenger RNA neosynthesis potentially harmful at long-term despite Bcl-2 over-expression. (C) 1999 IBRO. Published by Elsevier Science Ltd.
引用
收藏
页码:653 / 664
页数:12
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