Premium
Effects of zinc on SN56 cholinergic neuroblastoma cells
Author(s) -
Ronowska Anna,
GulHinc Sylwia,
Bielarczyk Hanna,
Pawełczyk Tadeusz,
Szutowicz Andrzej
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04786.x
Subject(s) - aconitase , zinc , metabolism , glycolysis , pyruvate dehydrogenase complex , enzyme , biochemistry , chemistry , citric acid cycle , cell , dehydrogenase , cytotoxic t cell , endocrinology , medicine , biology , in vitro , organic chemistry
Zinc is a trace element necessary for proper development and function of brain cells. However, excessive accumulation of zinc exerts several cytotoxic effects in the brain. The aim of this work was to see whether cytotoxic effects of zinc are quantitatively correlated with changes in acetyl‐CoA metabolism. The zinc levels up to 0.20 mmol/L caused concentration‐dependent inhibition of pyruvate dehydrogenase (PDH) activity that correlated with the increase in trypan blue‐positive fraction and the decrease in cultured cell number ( r = 0.96, p = 0.0001). Chronic exposure of cells to 0.15 mmol/L zinc decreased choline acetyltransferase and aconitase activities, cytoplasmic acetyl‐CoA and whole cell ATP level by 38%, 57%, 35%, and 62%, respectively but caused no change in mitochondrial acetyl‐CoA level and activities of other enzymes of glycolytic and tricarboxylic acid cycle. dl ‐α‐lipoamide when added simultaneously with zinc to cultured cells or their homogenates attenuated its chronic or acute suppressive effects. In homogenates of chronically Zn‐treated cells, lipoamide overcame PDH but not aconitase inhibition. Presented data indicate that acute‐transient elevation of zinc caused reversible inhibition of PDH, aconitase activities and acetyl‐CoA metabolism, which when prolonged could lead to irreversible enzyme inactivation yielding decrease in cell viability and secondary suppression of their cholinergic phenotype.