Abstract
The primary mechanism of cyanide (CN) intoxication is the inhibition of metabolism in the central nervous system. We determined the effects of CN on several biochemical processes in neuroblastoma x glioma hybrid NG108-15 cells, which possess numerous neuronal properties. These cells were not sensitive to a high concentration (1 mM) of NaCN, but became sensitive in the presence of the anaerobic glycolysis inhibitors sodium iodoacetate (IA) and 2-deoxyglucose (2-DG): cellular metabolic processes (e.g., DNA, RNA and protein synthesis) decreased, to about 40% of control due to treatment with 0.5 mM NaCN+0.05 mM IA and 0.1 mM NaCN+20 mM 2-DG. ATP in cells exposed to 0.01 or 0.1 mM NaCN+20 mM 2-DG was reduced 75% and 100%, respectively within one min. Pretreatment of cells with the CN antidote cobalt (II) chloride (CoCl2) (0.06–0.18 mM) for 5 min prevented the depression of both [3H]leucine incorporation and ATP synthesis due to 1 mM NaCN+20 mM 2-DG in a concentration-dependent manner. A proposed CN antidote alpha-ketoglutaric acid (disodium salt) also prevented the depression of cellular metabolism due to NaCN plus 2-DG. These results indicate that blocking anaerobic glycolysis makes NG108-15 cells sensitive to a low concentration of CN. Thus NG108-15 cells should be useful to study the mechanisms of neurotoxicity of CN and to test antidotes.
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Ray, P., Monroe, F.L., Berman, J.D. et al. Cyanide sensitive and insensitive bioenergetics in a clonal neuroblastoma x glioma hybrid cell line. Neurochem Res 16, 1121–1124 (1991). https://doi.org/10.1007/BF00966589
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DOI: https://doi.org/10.1007/BF00966589