title: Thiamine deficiency--induced partial necrosis and mitochondrial uncoupling in neuroblastoma cells are rapidly reversed by addition of thiamine.
abstract: Culture of neuroblastoma cells in a medium of low-thiamine concentration (6 nM) and in the presence of the transport inhibitor amprolium leads to the appearance of overt signs of necrosis; i.e., the chromatin condenses in dark patches, the oxygen consumption decreases, mitochondria are uncoupled, and their cristae are disorganized. Glutamate formed from glutamine is no longer oxidized and accumulates, suggesting that the thiamine diphosphate-dependent alpha-ketoglutarate dehydrogenase activity is impaired. When thiamine (10 microM) is added to the cells, the O2 consumption increases, respiratory control is restored, and normal cell and mitochondrial morphology is recovered within 1 h. Succinate, which is oxidized via the thiamine diphosphate-independent succinate dehydrogenase, is also able to restore a normal O2 consumption (with respiratory control) in digitonin-permeabilized thiamine-deficient cells. Our results therefore suggest that the slowing of the citric acid cycle is the main cause of the biochemical lesion induced by thiamine deficiency as observed in Wernicke's encephalopathy.
authors.affiliation: Laboratory of Bioenergetics, University of Liège, Sart-Tilman, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Bettendorff
authors.forename: F
authors.initials: F
authors.lastname: Sluse
authors.forename: G
authors.initials: G
authors.lastname: Goessens
authors.forename: P
authors.initials: P
authors.lastname: Wins
authors.forename: T
authors.initials: T
authors.lastname: Grisar
mesh_terms: D000670:Amprolium / Q000494:pharmacology; D008854:Microscopy, Electron; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure; D009336:Necrosis; D009447:Neuroblastoma / Q000473:pathology* / Q000503:physiopathology*; D013831:Thiamine / Q000494:pharmacology*; D013832:Thiamine Deficiency / Q000473:pathology* / Q000503:physiopathology*; D014407:Tumor Cells, Cultured
chemical_list: D000670:Amprolium; D013831:Thiamine