ADENOSINE PROTECTS CHICK EMBRYONIC SYMPATHETIC NEURONS FROM APOPTOTICDEATH BY 2'-DEOXYADENOSINE IMPORTANCE OF ATP IN APOPTOSIS

Our past work on nucleoside toxicity in sympathetic neurons has clearl y revealed that adenosine and 2'-deoxyadenosine (dAdo) have different mechanisms of action in inducing apoptotic death. For example, adenosi ne is toxic to neurons only during early phase of growth whereas dAdo kills even mature neurons. In this study, we hypothesize that dAdo-ind uced apoptosis is initiated when ATP concentration of sympathetic neur ons 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 full y prevented by adenosine treatment. Furthermore, we demonstrate that d epletion of ATP caused by dAdo was prevented by pretreatment with aden osine. These data suggest that intracellular accumulation of adenosine could play a neuroprotective role in preventing death associated with reduction in neuronal ATP concentration. (C) 1998 Published by Elsevi er Science Ireland Ltd. All rights reserved.