Adenosine protects chick embryonic sympathetic neurons from apoptotic death by 2′-deoxyadenosine - importance of ATP in apoptosis

• Published in: Neuroscience letters 1998-08, Vol.252 (3), p.163-166
• Main Authors: Wakade, Arun R, Wakade, Taruna D, Kulkarni, Jayant S
• Format: Article
• Language: English
• Subjects: Adenosine - pharmacology; Adenosine kinase; Animals; Apoptosis - drug effects; Apotosis; Biological and medical sciences; Chick Embryo; Deoxyadenosines - antagonists & inhibitors; Deoxyadenosines - toxicity; deoxyATP; Drug Evaluation, Preclinical; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - drug effects; Ganglia, Spinal - pathology; Neurons - drug effects; Neurons - pathology; Nucleoside toxicity; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; Program cell death; Sympathetic Nervous System - cytology; Sympathetic Nervous System - drug effects; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(98)00553-9

Our past work on nucleoside toxicity in sympathetic neurons has clearly revealed that adenosine and 2′-deoxyadenosine (dAdo) have different mechanisms of action in inducing apoptotic death. For example, adenosine is toxic to neurons only during early phase of growth whereas dAdo kills even mature neurons. In this study, we hypothesize that dAdo-induced apoptosis is initiated when ATP concentration of sympathetic neurons decreases below a critical level. To prove our hypothesis we used adenosine as a tool to replenish ATP levels of sympathetic neurons. We demonstrate that dAdo toxicity in mature sympathetic neurons was fully prevented by adenosine treatment. Furthermore, we demonstrate that depletion of ATP caused by dAdo was prevented by pretreatment with adenosine. These data suggest that intracellular accumulation of adenosine could play a neuroprotective role in preventing death associated with reduction in neuronal ATP concentration.