Acute and chronic effects of aluminum on acetyl-CoA and acetylcholine metabolism in differentiated and nondifferentiated SN56 cholinergic cells

Mechanisms of preferential loss of cholinergic neurons in the course of neu rodegenerative diseases are unknown. Therefore, we investigated whether dif ferentiation-evoked changes in acetyl-CoA and acetylcholine metabolism cont ribute to the susceptibility of cholinergic neuroblastoma to cytotoxic effe cts of Al. In SN56 cells differentiated with retinoic acid and dibutyryl cA MP (DC), pyruvate utilization and acetyl-CoA content were lower and acetylc holine level higher than in nondifferentiated cells (NC), respectively. In DC Al and Ca accumulations were 50% and 100%, respectively higher than in N C. Acute Al addition caused inhibition, whereas its chronic application had no effect on pyruvate utilization both in NC and in DC. On the other hand, in both experiments, Al evoked a greater decrease of acetyl-CoA level in D C than in NC. Acute addition of Al depressed acetylcholine release from DC to two times lower values than in NC. On the other hand, chronic addition o f Al increased ACh release from DC over twofold, being without effect on it s release from NC. These findings indicate that higher accumulation of Ca, along with low levels of acetyl-CoA, could make DC more susceptible to neur otoxic inputs than NC. Excessive acetylcholine release, evoked by Al, is li kely to increase acetyl-CoA utilization for resynthesis of the neurotransmi tter pool and cause deficit of this metabolite in DC. On the other hand, NC , owing to lower Ca accumulation, slower ACh metabolism, and higher level o f acetyl-CoA, would be less prone to these harmful conditions. (C) 2000 Wil ey-Liss, Inc.