PHOSPHORYLATION OF INITIATION-FACTOR-2-ALPHA SUBUNIT AND APOPTOSIS INCA2-TREATED CULTURED NEURONAL CELLS( IONOPHORE)

The initial step of protein synthesis is regulated by the eukaryotic i nitiation factor 2 (eIF-2) whose phosphorylation in the a subunit by s pecific kinases, as double-stranded RNA-dependent protein kinase (PKR) , produces an inhibition of the translational rates. Besides, intracel lular Ca2+ mobilization has been associated with an increase in the PK R activity. Our results show, in primary neuronal cultures, that the t reatment with the Ca2+ ionophore A23187 induces an increase in the pho sphorylation of the alpha subunit of eIF-2 (eIF-2 alpha) and inhibitio n of protein synthesis. Those biochemical changes run parallel to the appearance of specific apoptosis characteristics such as cell shrinkag e, segmentation of chromatin into small round bodies, and cleavage of DNA into 180 bp multimers. These results indicate that one of the targ ets during the process of apoptosis induced by the rise in the intrace llular Ca2+, could be eIF-2 factor.