Phosphorylation of initiation factor 2 alpha subunit and apoptosis in Ca2+ ionophore-treated cultured neuronal cells.
The initial step of protein synthesis is regulated by the eukaryotic initiation factor 2 (eIF-2) whose phosphorylation in the alpha subunit by specific kinases, as double-stranded RNA-dependent protein kinase (PKR), produces an inhibition of the translational rates. Besides, intracellular Ca2+ mobilization has been associated with an increase in the PKR activity. Our results show, in primary neuronal cultures, that the treatment with the Ca2+ ionophore A23187 induces an increase in the phosphorylation of the alpha subunit of eIF-2 (eIF-2 alpha) and inhibition of protein synthesis. Those biochemical changes run parallel to the appearance of specific apoptosis characteristics such as cell shrinkage, segmentation of chromatin into small round bodies, and cleavage of DNA into 180 bp multimers. These results indicate that one of the targets during the process of apoptosis induced by the rise in the intracellular Ca2+, could be eIF-2 factor.
Alcázar
A
A
Dpto. Investigación, Hospital Ramón y Cajal, Madrid, Spain.
Bazán
E
E
Rivera
J
J
Salinas
M
M
D000818:Animals; D017209:Apoptosis; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D004586:Electrophoresis; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D019892:eIF-2 Kinase
D015852:Eukaryotic Initiation Factor-2; D000001:Calcimycin; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D002118:Calcium