title: Cyanide sensitive and insensitive bioenergetics in a clonal neuroblastoma x glioma hybrid cell line.
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.
authors.affiliation: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
authors.forename: P
authors.initials: P
authors.lastname: Ray
authors.forename: F L
authors.initials: FL
authors.lastname: Monroe
authors.forename: J D
authors.initials: JD
authors.lastname: Berman
authors.forename: J
authors.initials: J
authors.lastname: Fiedler
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002999:Clone Cells; D003035:Cobalt / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D005910:Glioma; D006822:Hybrid Cells / Q000187:drug effects / Q000378:metabolism; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis; D012966:Sodium Cyanide / Q000494:pharmacology*
chemical_list: D007461:Iodoacetates; D003035:Cobalt; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; C018021:cobaltous chloride; D007930:Leucine; D012966:Sodium Cyanide; D019807:Iodoacetic Acid