Effects of lead on cholinergic SN56 neuroblastoma cells

Abstract

Age-dependent accumulation of lead in brain has been implicated in the pathomechanisms of Alzheimer.s disease. The aim of this work was to investigate whether cholinotoxic effects of lead may result from alterations in acetyl-CoA metabolism. One day exposure of differentiated SN56 cholinergic neuroblastoma cells to 0.5 μ mol/L lead or 0.01 mmol/L amyloid-β1-42 increased fraction of nonviable cells to about 20%. Suppression of choline acetyltransferase activity occurred only in the presence of fresh amyloid-β1-42, whereas lead was ineffective. All agents in combination caused suppression of acetyl-CoA in cytoplasm and mitochondria down to 19% and 34% of controls, respectively. Inverse correlation was observed between whole cell acetyl-CoA level and fraction of nonviable cells at different combinations of lead and other neurotoxic compounds. It indicates that lead had no primary suppressive effect on cholinergic phenotype but, at least in part, exerted cytotoxic influence on cholinergic neurons through the decrease of their acetyl-CoA. © 2008 by Polish Neuroscience Society - PTBUN, Nencki Institute of Experimental Biology.