Bulletin of Experimental Biology and Medicine

, Volume 164, Issue 3, pp 298–303 | Cite as

The Role of Succinate in Regulation of Immediate HIF-1α Expression in Hypoxia

  • L. D. Lukyanova
  • Yu. I. Kirova
  • E. L. Germanova
Article

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.

Key Words

succinate HIF-1α GABA shunt hypoxia 

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References

  1. 1.
    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.Google Scholar
  2. 2.
    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.CrossRefPubMedGoogle Scholar
  3. 3.
    Kondrashova MN. Interaction of carbonic acid reamination and oxidation processes at various functional states of tissue. Biochemistry (Moscow). 1991;56(3):388-405.Google Scholar
  4. 4.
    Luk’yanova LD. Bioenergetic hypoxia: Definition, mechanisms, and methods of correction. Bull. Exp. Biol. Med. 1997;124(3):835-843.CrossRefGoogle Scholar
  5. 5.
    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.CrossRefPubMedGoogle Scholar
  6. 6.
    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.CrossRefPubMedGoogle Scholar
  7. 7.
    Modern Problems of Biochemistry. Methods. Chirkin AA, ed. Minsk, 2013. Russian.Google Scholar
  8. 8.
    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.PubMedGoogle Scholar
  9. 9.
    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.CrossRefGoogle Scholar
  10. 10.
    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.PubMedGoogle Scholar
  11. 11.
    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.CrossRefGoogle Scholar
  12. 12.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell. 2012;148(3):399-408.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Semenza GL. Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (Bethesda). 2009;24:97-106.PubMedGoogle Scholar
  15. 15.
    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.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • L. D. Lukyanova
    • 1
  • Yu. I. Kirova
    • 1
  • E. L. Germanova
    • 1
  1. 1.Research Institute of General Pathology and PathophysiologyMoscowRussia

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