Effects of lead on cholinergic SN56 neuroblastoma cells.
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 micromol/L lead or 0.01 mmol/L amyloid-beta1-42, increased fraction of nonviable cells to about 2%. Suppression of choline acetyltransferase activity occurred only in the presence of fresh amyloid-beta1-42, 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.
Jankowska-Kulawy
Agnieszka
A
Department of Laboratory Medicine, Medical University of Gdańsk, Gdańsk, Poland.
Gul-Hinc
Sylwia
S
Bielarczyk
Hanna
H
Suszkiw
Janusz B
JB
Pawełczyk
Tadeusz
T
Dyś
Aleksandra
A
Szutowicz
Andrzej
A
D000105:Acetyl Coenzyme A / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity; D001932:Brain Neoplasms / Q000473:pathology; D002452:Cell Count; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D007854:Lead / Q000633:toxicity; D020263:Lead Poisoning, Nervous System / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D010275:Parasympathetic Nervous System / Q000473:pathology*; D014343:Trypan Blue
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D007854:Lead; D000105:Acetyl Coenzyme A; D014343:Trypan Blue