Hypoxia-induced immediate expression of transcription factor HIF-1α in the brain cortex is regulated by succinate produced in both the tricarbonic acid cycle and GABA shunt reactions and is induced by succinate-containing drugs. These facts prove the existence of succinate-dependent signalling regulation involved in immediate and delayed molecular adaptation and increased body resistance to oxygen deficiency, where succinate acts as a signal molecule. The intensity of this process differs in animals with low and high resistance to hypoxia.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Eshchenko ND. Energy metabolism in the brain. Biochemistry of the Brain. Ashmarin IP, Stukalov PV, Eshchenko ND, eds. St. Petersburg, 1999. P. 124-168. Russian.
Kirova YI, Germanova EL, Lukyanova LD. Phenotypic features of the dynamics of HIF-1α levels in rat neocortex in different hypoxia regimens. Bull. Exp. Biol. Med. 2013;154(6):718-722.
Kondrashova MN. Interaction of carbonic acid reamination and oxidation processes at various functional states of tissue. Biochemistry (Moscow). 1991;56(3):388-405.
Luk’yanova LD. Bioenergetic hypoxia: Definition, mechanisms, and methods of correction. Bull. Exp. Biol. Med. 1997;124(3):835-843.
Lukyanova LD, Germanova EL, Kopaladze RA. Development of resistance of an organism under various conditions of hypoxic preconditioning: role of the hypoxic period and reoxygenation. Bull. Exp. Biol. Med. 2009;147(4):400-404.
Lukyanova LD, Germanova EL, Tsybina TA, Chernobaeva GN. Energotropic effect of succinate-containing derivatives of 3-hydroxypyridine. Bull. Exp. Biol. Med. 2009;148(4):587-591.
Modern Problems of Biochemistry. Methods. Chirkin AA, ed. Minsk, 2013. Russian.
Chilov D, Camenisch G, Kvietikova I, Ziegler U, Gassmann M, Wenger RH. Induction and nuclear translocation of hypoxia-inducible factor-1 (HIF-1): heterodimerization with ARNT is not necessary for nuclear accumulation of HIF-1alpha. J. Cell. Sci. 1999;112(Pt 8):1203-1212.
Hawkins BJ, Levin MD, Doonan PJ, Petrenko NB, Davis CW, Patel VV, Madesh M. Mitochondrial complex II prevents hypoxic but not calcium- and proapoptotic Bcl-2 protein-induced mitochondrial membrane potential loss. J. Biol. Chem. 2010;285(34):26 494-26 505.
Komaromy-Hiller G, Sundquist PD, Jacobsen LJ, Nuttall KL. Serum succinate by capillary zone electrophoresis: marker candidate for hypoxia. Ann. Clin. Lab. Sci. 1997;27(2):163-168.
Lukyanova LD. Mitochondria signaling in adaptation to hypoxia. Int. J. Physiol. Pathophys. 2014;5(4):363-381. doi: https://doi.org/10.1615/IntJPhysPathophys.v5.i4.90.
Lukyanova LD, Kirova YI. Mitochondria-controlled signaling mechanisms of brain protection in hypoxia. Front. Neurosci. 2015;9:320. doi: https://doi.org/10.3389/fnins.2015.00320.
Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell. 2012;148(3):399-408.
Semenza GL. Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (Bethesda). 2009;24:97-106.
Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol. Cell. Biol. 1992;12(12):5447-5454.
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 164, No. 9, pp. 273-279, September, 2017
Rights and permissions
About this article
Cite this article
Lukyanova, L.D., Kirova, Y.I. & Germanova, E.L. The Role of Succinate in Regulation of Immediate HIF-1α Expression in Hypoxia. Bull Exp Biol Med 164, 298–303 (2018). https://doi.org/10.1007/s10517-018-3976-2
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-018-3976-2