Neurochemical Journal

, Volume 13, Issue 2, pp 145–155 | Cite as

The Effect of Severe Hypoxia on HIF1- and Nrf2-Mediated Mechanisms of Antioxidant Defense in the Rat Neocortex

  • K. V. SarievaEmail author
  • A. Yu. Lyanguzov
  • O. V. Galkina
  • O. V. Vetrovoy
Experimental Articles


The transcription factor (TF) HIF1 is one of the most important factors of adaptation to chronic cerebral hypoxia. However, under the conditions of acute hypoxia and reoxygenation, the stress response TF (NRF2) becomes important. The interaction between these proteins at the level of regulation of antioxidant defense and glucose metabolism has been shown previously in hypoxia-sensitive cancer tumors. Here, we have studied the effect of severe hypobaric hypoxia (SH) on HIF1- and NRF2-dependent processes in the rat neocortex. We revealed the joint regulation of glutathione-dependent antioxidant systems by these proteins, which influenced the total antiradical activity and the cellular redox status. In particular, HIF1 inhibition prevented the SH-induced oxidative shift 23 h after reoxygenation, which was accompanied by an increase in the content of total glutathione and the activity of glutathione reductase. Both of these effects were NRF2-dependent, which suggests that this transcription factor is activated in response to SH in combination with HIF1 inhibition. The data confirm the previous hypothesis about the maladaptive effect of HIF1 under the conditions of acute hypoxia and reoxygenation and point to the contribution of NRF2 the protective mechanisms in the post-hypoxic period. The hypothesis of interaction between these transcription factors in the (post)hypoxic period requires further verification and may have substantial influence on understanding the molecular pathomechanisms of cerebral hypoxia.


NRF2 HIF1 glutathione glutathione-dependent antioxidant system antioxidant activity redox status neocortex severe hypobaric hypoxia 


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Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • K. V. Sarieva
    • 1
    • 2
    Email author
  • A. Yu. Lyanguzov
    • 3
  • O. V. Galkina
    • 2
  • O. V. Vetrovoy
    • 1
    • 2
  1. 1.Pavlov Institute of PhysiologyRussian Academy of SciencesSt. PetersburgRussia
  2. 2.Chair of BiochemistrySt. Petersburg State University, Faculty of BiologySt. PetersburgRussia
  3. 3.Observatory of Environmental Safety Resource Center, Research ParkSt. Petersburg State UniversitySt. PetersburgRussia

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