Bicyclonucleosides and ring-chain interconversion.

Four types of bicyclonucleosides differing in the easiness of their ring-chain interconversion have been prepared, some exhibited anti-HIV activity and the ratio of their cyclic and open-chain forms could have some bearing on their biological activity.

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

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 level without repercussion at the messenger RNA level. Axotomy induces cell death messenger RNA neosynthesis potentially harmful at long-term despite Bcl-2 over-expression.