Article (Scientific journals)
Thiamine Deficiency in Cultured Neuroblastoma Cells: Effect on Mitochondrial Function and Peripheral Benzodiazepine Receptors
Bettendorff, Lucien; Goessens, Guy; Sluse, Francis et al.
1995In Journal of Neurochemistry, 64 (5), p. 2013-2021
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Abstract :
[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Bettendorff, Lucien  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Goessens, Guy ;  Université de Liège - ULiège > Services généraux (Faculté des sciences) > Relations académiques et scientifiques (Sciences)
Sluse, Francis ;  Université de Liège - ULiège > Département des sciences de la vie > Bioénergétique et physiologie cellulaire
Wins, Pierre
Bureau, Michel
Laschet, Jacques
Grisar, Thierry ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Language :
English
Title :
Thiamine Deficiency in Cultured Neuroblastoma Cells: Effect on Mitochondrial Function and Peripheral Benzodiazepine Receptors
Publication date :
1995
Journal title :
Journal of Neurochemistry
ISSN :
0022-3042
eISSN :
1471-4159
Publisher :
Blackwell, Oxford, United Kingdom
Volume :
64
Issue :
5
Pages :
2013-2021
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 23 January 2009

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