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Thiamine Deficiency‐Induced Partial Necrosis and Mitochondrial Uncoupling in Neuroblastoma Cells Are Rapidly Reversed by Addition of Thiamine
Author(s) -
Bettendorff L.,
Sluse F.,
Goessens G.,
Wins P.,
Grisar T.
Publication year - 1995
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 - 10.1046/j.1471-4159.1995.65052178.x
Subject(s) - thiamine , glutamine , biochemistry , citric acid cycle , biology , mitochondrion , succinate dehydrogenase , chemistry , endocrinology , medicine , enzyme , amino acid
Culture of neuroblastoma cells in a medium of low‐thiamine concentration (6 n M ) 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 α‐ketoglutarate dehydrogenase activity is impaired. When thiamine (10 µ M ) is added to the cells, the O 2 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 O 2 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.