title: Cellular thiamine status is coupled to function of mitochondrial 2-oxoglutarate dehydrogenase.
abstract: Decreased thiamine and reduced activity of thiamine diphosphate (ThDP)-dependent 2-oxoglutarate dehydrogenase (OGDH) cause neurodegeneration. We hypothesized on concerted cell-specific regulation of the thiamine metabolism and ThDP-dependent reactions. We identified a smaller thiamine pool, a lower expression of the mitochondrial ThDP transporter, and a higher expression of OGDH in rat astrocytes versus neuroblastoma N2A. According to the data, the astrocytic OGDH may be up-regulated by an increase in intracellular ThDP, while the neuroblastomal OGDH functions at full ThDP saturation. Indeed, in rat astrocytes and brain cortex, OGDH inhibition by succinyl phosphonate (SP) enlarged the pool of thiamine compounds. Increased ThDP level in response to the OGDH inhibition presumably up-regulated the enzyme to compensate for a decrease in reducing power which occurred in SP-treated astrocytes. Under the same SP treatment of N2A cells, their thiamine pool and reducing power were unchanged, although SP action was evident from accumulation of glutamate. The presented data indicate that functional interplay between OGDH, other proteins of the tricarbocylic acid cycle and proteins of thiamine metabolism is an important determinant of physiology-specific networks and their homeostatic mechanisms.
authors: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskije gori 1, 119992 Moscow, Russia.
authors: G
authors: G
authors: Mkrtchyan
authors: Faculty of Biology, Lomonosov Moscow State University, Leninskije gori 1, 119992 Moscow, Russia; Faculty of Nano-, Bio-, Informational and Cognitive Technologies at Moscow Institute of Physics and Technology, Maximova Street, 123098 Moscow, Russia.
authors: A
authors: A
authors: Graf
authors: GIGA-Neurosciences, University of Liege, Avenue Hippocrate, 15, 4000 Liege, Belgium.
authors: L
authors: L
authors: Bettendorff
authors: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskije gori 1, 119992 Moscow, Russia; A.N.Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskije gori 1, 119992 Moscow, Russia. Electronic address: vbunik@belozersky.msu.ru.
authors: V
authors: V
authors: Bunik
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D063065:Organophosphonates / Q000378:metabolism / Q000494:pharmacology; D013386:Succinates / Q000378:metabolism / Q000494:pharmacology; D013831:Thiamine / Q000378:metabolism*; D013835:Thiamine Pyrophosphate / Q000378:metabolism
chemical_list: D063065:Organophosphonates; D013386:Succinates; C099145:succinyl phosphonate; D018698:Glutamic Acid; D007655:Ketoglutarate Dehydrogenase Complex; D013835:Thiamine Pyrophosphate; D013831:Thiamine
keywords: 2-Oxoglutarate dehydrogenase; Astrocytes; Neuroblastoma; Stress response; Thiamine; Tricarboxylic acid cycle