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Energotropic Effects of Intermittent Hypoxia: Role of Succinate-Dependent Signaling

  • Ludmila D. LukyanovaEmail author
  • Yu I. Kirova
  • Elina L. Germanova
Chapter

Abstract

This chapter focuses on a bioenergetic mechanism for development of urgent and long-term adaptation to hypoxia. Hypoxia induces reprogramming of respiratory chain function and switching from oxidation of NAD-related substrates (complex I) to succinate oxidation (complex II). Transient, reversible, compensatory activation of respiratory chain complex II is a major mechanism of urgent adaptation to hypoxia, which is necessary for (1) succinate-related energy synthesis in the conditions of oxygen shortage and formation of urgent resistance in the body, (2) succinate-related stabilization of HIF-1α and initiation of its transcriptional activity related with formation of long-term adaptation, and (3) succinate-dependent activation of the succinate-specific receptor GPR91. Therefore, succinate is a signaling molecule, and succinate effects in hypoxia occur at three levels, intramitochondrial, intracellular, and intercellular. In these settings, succinate displays antihypoxic and antiradical activities. Suppression of free-radical processes in early phase of hypoxia potentiates effects of succinate and facilitates development of urgent adaptation to hypoxia. The chapter considers tactics and strategy for development of the antihypoxic defense and of antihypoxants with energotropic properties.

Keywords

Hypobaric Hypoxia Hypoxic Exposure Acute Hypoxia Oxygen Shortage Succinate Oxidation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AHBH

Acute hypobaric hypoxia

ATP

Adenosine triphosphate

CD

Conjugated dienes

FAD

Flavin adenine nucleotides

GPR91

Succinate-related guanine nucleotide binding protein-coupled receptor

GSH

Reduced glutathione

GSSG

Oxidized glutathione

HIF

Hypoxia-inducible factor

HR

High-resistance rats

HSP

Heat shock proteins

INH

Interval normobaric hypoxia

LOOH

Lipid hydroperoxides

LP

Lipid peroxidation

LR

Low-resistance rats

NAD

Nicotine adenine nucleotides

NBH

Normobaric hypoxia

PC

Phosphocreatine

ROS

Reactive oxygen species

SDH

Succinate dehydrogenase

TBARS

Thiobarbituric acid reactive substances.

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Copyright information

© Springer-Verlag London 2012

Authors and Affiliations

  • Ludmila D. Lukyanova
    • 1
    Email author
  • Yu I. Kirova
    • 1
  • Elina L. Germanova
    • 1
  1. 1.Institute of General Pathology and Pathophysiology, Russian Academia of Medical SciencesMoscowRussia

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