Adenosine induces apoptosis by inhibiting mRNA and protein synthesis in chick embryonic sympathetic neurons.
Our previous work has established that adenosine is toxic to chick embryonic sympathetic neurons and kills freshly plated neurons by a process of apoptosis. Although the exact mechanism remains unknown, we found that phosphorylation of adenosine was essential to the toxicity. Using markers for RNA ([3H]uridine) and protein ([35S]methionine) synthesis we demonstrate here that in freshly plated sympathetic neurons adenosine inhibits RNA and protein synthesis by about 50%. The inhibitory 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 protein 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.
Kulkarni
J S
JS
Department of Pharmacology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
Przywara
D A
DA
Wakade
T D
TD
Wakade
A R
AR
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011742:Pyrimidine Nucleotides / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D011506:Proteins; D011742:Pyrimidine Nucleotides; D012333:RNA, Messenger; D000241:Adenosine