BACKGROUND AND AIMS: Excess of zinc ions and intermittent hypoxia both cause neurodegeneration by disruption in energy metabolism and oxidative stress, resulting in diminished pyruvate dehydrogenase complex (PDHC) and aconitase activity and consequent shortages in acetyl-CoA. This deficiency may be particularly dangerous for cholinergic neurons as they consume acetyl-CoA in additional pathway of acetylcholine synthesis apart from energy production. Aim of our study was to investigate effect of hypoxia on acetylCoA metabolism in neuronal cells under cytotoxic conditions. METHODS: The SH-SY5Y neuroblastoma cells were recognized as an in vitro model of brain cholinergic neurons after differentiating with all-trans-retinoic acid and cAMP. Hypoxic conditions were induced by 24 h (chronic) exposition of SH-SY5Y cells to cobalt ions (Co). Zinc (Zn) ions were used to evoke cytotoxicity. RESULTS: Chronic exposition of SH-SY5Y NC to 0.2 mM and 0.5 mM Co decreased cells number by 22% and 53%, respectively. The activities of PDHC and aconitase were reduced by 70% (0.2 mM Co) and over 75% (0.5 mM Co). IDH activity, in both concentrations, was decreased by 18%. The level of acetyl-CoA in SH-SY5Y NC was 28.4 pmol/mg of protein and chronic exposition of SH-SY5Y to 0.5 mM Co decreased acetyl-CoA level by about 60%. Chronic exposure of SH-SY5Y DC to 0.2 mM and 0.5 mM Co decreased number of cells by 28 and 60%, respectively, reduced activities of PDHC by 52% (0.2 mM) and 31% (0.5 mM Co). Aconitase activity was decreased by 77 and 90%, respectively. Activity of NADP-IDH and level of acetyl-CoA were also diminished regardless of the cobalt concentration by approximately 28% and 30%, respectively. In both groups addition of 0.1 mM Zn-aggravated cells mortality. CONCLUSION: Presented data indicate that hypoxia enhance cytotoxic effects of Zn in highly differentiated cholinergic cells. Supported by Ministry of Research and Higher Education projects: MN 01-0058/08 and ST-57, IP 2011046071.
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