Effect of hypoxia on mitochondrial enzymes and ultrastructure in the brain cortex of rats with different tolerance to oxygen shortage

Abstract

The mitochondrial structure and the contents of subunits (NDUFV2, SDHA, Cyt b, COX1) of mitochondrial respiratory complexes I–IV as well as of the hypoxia-inducible factor (HIF-1α) in the brain cortex (BC) of rats with high resistance (HR) and low resistance (LR) to hypoxia were studied for the first time depending on the severity of hypoxia. Different regimes of 30-min hypobaric hypoxia (pO2 14, 10, and 8%) were used. It was found that cortical mitochondria responded to 30-min hypobaric hypoxia of different severity with typical and progressing changes in mitochondrial structure and function of mitochondrial enzymes. Under 14 and 10% hypoxia, animals developed compensatory structural and metabolic responses aimed at supporting the cell energy homeostasis. Consequently, these hypoxia regimes can be used for treatment in pressure chambers. At the same time, decreasing the oxygen concentration in the inhaled air to 8% led to the appearance of destructive processes in brain mitochondria. The features of mitochondrial ultrastructure and the function of respiratory enzymes in the BC of HR and LR rats exposed to normoxic and hypoxic conditions suggest that the two types of animals had two essentially distinct functional and metabolic patterns determined by different efficiency of the energy apparatus. The development of adaptive and destructive responses involved different metabolic pathways of the oxidation of energy substrates and different efficiency of the functioning of mitochondrial respiratory carriers.

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Abbreviations

BC:

brain cortex

HBH:

acute hypobaric hypoxia

LR:

low-resistance rats

HR:

high-resistance rats

MC:

mitochondrial enzyme catalytic subunits

NDUFV2:

NADH dehydrogenase [ubiquinone] flavoprotein 2

SDHA:

flavochrome subunit A of succinate dehydrogenase

COX1:

cytochrome c oxidase subunit

HIF-1α:

hypoxia-inducible factor 1 alpha subunit

RDU:

relative densitometric units

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Acknowledgements

The work was supported by the Russian Science Foundation (RSF) (project No. 16-15-00157 to G.D.). The procedure of animal treatment and the work of technicians were supported by the Russian Foundation for Basic Research (RFBR) (project No. 18-34-00297mol_a to N.B.).

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Correspondence to Galina D. Mironova.

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Mironova, G.D., Pavlik, L.L., Kirova, Y.I. et al. Effect of hypoxia on mitochondrial enzymes and ultrastructure in the brain cortex of rats with different tolerance to oxygen shortage. J Bioenerg Biomembr 51, 329–340 (2019). https://doi.org/10.1007/s10863-019-09806-7

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Keywords

  • Hypoxia
  • Mitochondrial ultrastructure
  • Respiratory chain complexes
  • Hypoxia-inducible factor 1α
  • Cytochrome b
  • Resistance to hypoxia