ADENOSINE INDUCES APOPTOSIS BY INHIBITING MESSENGER-RNA AND PROTEIN-SYNTHESIS IN CHICK EMBRYONIC SYMPATHETIC NEURONS

Our previous work has established that adenosine is toxic to chick emb ryonic sympathetic neurons and kills freshly plated neurons by a proce ss of apoptosis. Although the exact mechanism remains unknown, we foun d that phosphorylation of adenosine was essential to the toxicity. Usi ng markers for RNA ([H-3]uridine) and protein ([S-35]methionine) synth esis we demonstrate here that in freshly plated sympathetic neurons ad enosine inhibits RNA and protein synthesis by about 50%. The inhibitor y effects of adenosine on RNA and protein synthesis, and increased ATP synthesis were blocked by adenosine kinase inhibitor, suggesting that phosphorylated products are responsible for inhibition of RNA and pro tein synthesis and cell death. Adenosine-induced inhibition of RNA and protein synthesis in neuronal cells provides a new role for adenosine in the regulation of cell function. (C) 1998 Published by Elsevier Sc ience Ireland Ltd. All rights reserved.