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Open AccessArticle

Hypoxic Adaptation of Mitochondrial Metabolism in Rat Cerebellum Decreases in Pregnancy

1
Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
2
Faculty of Nano-, Bio-, Informational and Cognitive and Socio-humanistic Sciences and Technologies at Moscow Institute of Physics and Technology, 123098 Moscow, Russia
3
A.N. Belozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia
4
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia
5
Вiochemistry Department, Sechenov University, 119048 Moscow, Russia
*
Author to whom correspondence should be addressed.
Cells 2020, 9(1), 139; https://doi.org/10.3390/cells9010139 (registering DOI)
Received: 29 November 2019 / Revised: 29 December 2019 / Accepted: 2 January 2020 / Published: 7 January 2020
(This article belongs to the Special Issue Mitochondria in Health and Diseases)
Function of brain amino acids as neurotransmitters or their precursors implies changes in the amino acid levels and/or metabolism in response to physiological and environmental challenges. Modelling such challenges by pregnancy and/or hypoxia, we characterize the amino acid pool in the rat cerebellum, quantifying the levels and correlations of 15 amino acids and activity of 2-oxoglutarate dehydrogenase complex (OGDHC). The parameters are systemic indicators of metabolism because OGDHC limits the flux through mitochondrial TCA cycle, where amino acids are degraded and their precursors synthesized. Compared to non-pregnant state, pregnancy increases the cerebellar content of glutamate and tryptophan, decreasing interdependence between the quantified components of amino acid metabolism. In response to hypoxia, the dependence of cerebellar amino acid pool on OGDHC and the average levels of arginine, glutamate, lysine, methionine, serine, phenylalanine, and tryptophan increase in non-pregnant rats only. This is accompanied by a higher hypoxic resistance of the non-pregnant vs. pregnant rats, pointing to adaptive significance of the hypoxia-induced changes in the cerebellar amino acid metabolism. These adaptive mechanisms are not effective in the pregnancy-changed metabolic network. Thus, the cerebellar amino acid levels and OGDHC activity provide sensitive markers of the physiology-dependent organization of metabolic network and its stress adaptations. View Full-Text
Keywords: amino acid neurotransmitter; cerebellar amino acid metabolism; hypoxia; 2-oxoglutarate dehydrogenase; tricarboxylic acid cycle amino acid neurotransmitter; cerebellar amino acid metabolism; hypoxia; 2-oxoglutarate dehydrogenase; tricarboxylic acid cycle
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MDPI and ACS Style

Graf, A.; Trofimova, L.; Ksenofontov, A.; Baratova, L.; Bunik, V. Hypoxic Adaptation of Mitochondrial Metabolism in Rat Cerebellum Decreases in Pregnancy. Cells 2020, 9, 139.

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