Synthesis of specific proteins in trophic factor-deprived neurons undergoing apoptosis.

Apoptosis, also known as programmed cell death, is a mechanism used by different tissues to regulate their cell content. In the nervous system, this process is supposed to adjust the final number of neurons to the number of the target cells they are innervating. The demonstration that, in several systems in vitro and in vivo, neuronal apoptosis can be prevented by inhibiting RNA or protein synthesis suggests that an activation of gene expression is required in the cells that are going to die. The genes involved and their products, named "killer proteins," are not known in the superior vertebrates. In order to identify such proteins, we have used and characterized an in vitro model consisting of neurons derived from 8-day-old embryonic chicken ciliary ganglia. RNA and protein synthesis inhibitors can prevent the death of these neurons when they are deprived of trophic support. Comparing the synthesis of proteins in trophic-supported neurons with that in trophic-deprived neurons by the use of two-dimensional polyacrylamide gel electrophoresis, we have observed that several proteins were overexpressed reproducibly in the apoptotic cells. We found that all these proteins are localized in the nucleus, suggesting that they may be transcription regulators.