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Thiamine Deficiency-Induced Partial Necrosis and Mitochondrial Uncoupling in Neuroblastoma Cells Are Rapidly Reversed by Addition of Thiamine (1995)

Bettendorff, L. ; Sluse, F. ; Goessens, G. ; [et al.]

Oxford, UK : Blackwell Science Ltd

Journal of neurochemistry 65 (1995), S. 0

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ISSN: 1471-4159

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Medicine

Notes: 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 α-ketoglutarate dehydrogenase activity is impaired. When thiamine (10 µM) 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.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1046/j.1471-4159.1995.65052178.x

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Thiamine, Thiamine Phosphates, and Their Metabolizing Enzymes in Human Brain (1996)

Bettendorff, L. ; Mastrogiacomo, F. ; Kish, S. J. ; [et al.]

Oxford, UK : Blackwell Science Ltd

Journal of neurochemistry 66 (1996), S. 0

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ISSN: 1471-4159

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Medicine

Notes: Abstract: Total thiamine (the sum of thiamine and its phosphate esters) concentrations are two- to fourfold lower in human brain than in the brain of other mammals. There were no differences in the total thiamine content between biopsied and autopsied human brain, except that in the latter, thiamine triphosphate was undetectable. The main thiamine phosphate-metabolizing enzymes could be detected in autopsied brain, and the kinetic parameters were comparable to those reported in other species. Thiamine diphosphate levels were lowest in hippocampus (15 ± 4 pmol/mg of protein) and highest in mammillary bodies (24 ± 4 pmol/mg of protein). Maximal levels of thiamine and its phosphate ester were found to be present at birth. In parietal cortex and globus pallidus, mean levels of total thiamine in the oldest age group (77–103 years) were, respectively, 21 and 26% lower than those in the middle age group (40–55 years). Unlike cerebral cortex, the globus pallidus showed a sharp drop in thiamine diphosphate levels during infancy, with concentrations in the oldest group being only ∼50% of the levels present during the first 4 months of life. These data, consistent with previous observations conducted in blood, suggest a tendency toward decreased thiamine status in older people.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1046/j.1471-4159.1996.66010250.x

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Thiamine Deficiency in Cultured Neuroblastoma Cells: Effect on Mitochondrial Function and Peripheral Benzodiazepine Receptors (1995)

Bettendorff, L. ; Goessens, G. ; Sluse, F. ; [et al.]

Oxford, UK : Blackwell Science Ltd

Journal of neurochemistry 64 (1995), S. 0

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ISSN: 1471-4159

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Medicine

Notes: Abstract: When neuroblastoma cells were transferred to a medium of low (6 nM) thiamine concentration, a 16-fold decrease in total intracellular thiamine content occurred within 8 days. Respiration and ATP levels were only slightly affected, but addition of a thiamine transport inhibitor (amprolium) decreased ATP content and increased lactate production. Oxygen consumption became low and insensitive to oligomycin and uncouplers. At least 25% of mitochondria were swollen and electron translucent. Cell mortality increased to 75% within 5 days. [3H]PK 11195, a specific ligand of peripheral benzodiazepine receptors (located in the outer mitochondrial membrane) binds to the cells with high affinity (KD = 1.4 ± 0.2 nM). Thiamine deficiency leads to an increase in both Bmax and KD. Changes in binding parameters for peripheral benzodiazepine receptors may be related to structural or permeability changes in mitochondrial outer membranes. In addition to the high-affinity (nanomolar range) binding site for peripheral benzodiazepine ligands, there is a low-affinity (micromolar range) saturable binding for PK 11195. At micromolar concentrations, peripheral benzodiazepines inhibit thiamine uptake by the cells. Altogether, our results suggest that impairment of oxidative metabolism, followed by mitochondrial swelling and disorganization of cristae, is the main cause of cell mortality in severely thiamine-deficient neuroblastoma cells.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1046/j.1471-4159.1995.64052013.x

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Low Thiamine Diphosphate Levels in Brains of Patients with Frontal Lobe Degeneration of the Non-Alzheimer's Type (1997)

Bettendorff, L. ; Mastrogiacomo, F. ; Wins, P. ; [et al.]

Oxford, UK : Blackwell Science Ltd

Journal of neurochemistry 69 (1997), S. 0

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ISSN: 1471-4159

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Medicine

Notes: Abstract: We compared the thiamine and thiamine phosphate contents in the frontal, temporal, parietal, and occipital cortex of six patients with frontal lobe degeneration of the non-Alzheimer's type (FNAD) or frontotemporal dementia with five age-, postmortem delay-, and agonal status-matched control subjects. Our results reveal a 40–50% decrease in thiamine diphosphate (TDP) in the cortex of FNAD patients, whereas thiamine monophosphate was increased 49–119%. TDP synthesizing and hydrolyzing enzymes were unaffected. The activity of citrate synthase, a mitochondrial marker enzyme, was decreased in the frontal cortex of patients with FNAD, but no correlation with TDP content was found. These results suggest that decreased contents of TDP, which is essentially mitochondrial, is a specific feature of FNAD. As TDP is an essential cofactor for oxidative metabolism and neurotransmitter synthesis, and because low thiamine status (compared with other species) is a constant feature in humans, a nearly 50% decrease in cortical TDP content may contribute significantly to the clinical symptoms observed in FNAD. This study also provides a basis for a trial of thiamine, to improve the cognitive status of the patients.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1046/j.1471-4159.1997.69052005.x

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