Relationships between cholinergic phenotype and acetyl-CoA level in hybrid murine neuroblastoma cells of septal origin.

High susceptibility of cholinergic neurons to neurotoxic signals may result from their utilization of acetyl-CoA for both energy production and acetylcholine synthesis. SN56 cholinergic cells were transfected stably with cDNA for choline acetyltransferase. Transfected cells (SN56ChAT2) expressed choline acetyltransferase activity and acetylcholine content, 17 times and 2 times higher, respectively, than did nontransfected cells. Transfection did not change pyruvate dehydrogenase but decreased the acetyl-CoA level by 62%. Differentiation by cAMP and retinoic acid caused an increase of choline acetyltransferase activity and decrease of acetyl-CoA levels in both cell lines. Negative correlation was found between choline acetyltransferase activity and acetyl-CoA level in these cells. SN56ChAT2 cells were more susceptible to excess NO than were native SN56 cells, as evidenced by the thiazolyl blue reduction assay. Thus, the sensitivity of cholinergic neurons to pathologic conditions may depend on the cholinergic phenotype-dependent availability of acetyl-CoA. Copyright 2003 Wiley-Liss, Inc.