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Metabolic Reprogramming of Trophoblast Cells in Response to Hypoxia

  • E. N. Knyazev
  • G. S. Zakharova
  • L. A. Astakhova
  • I. M. Tsypina
  • A. G. TonevitskyEmail author
  • G. T. Sukhikh
Article

Hypoxia of trophoblast cells is an important regulator of normal development of the placenta. However, some pathological states associated with hypoxia, e.g. preeclampsia, impair the functions of placental cells. Oxyquinoline derivative inhibits HIF-prolyl hydroxylase by stabilizing HIF-1 transcription complex, thus modeling cell response to hypoxia. In human choriocarcinoma cells BeWo b30 (trophoblast model), oxyquinoline increased the expression of a core hypoxia response genes along with up-regulation of NOS3, PDK1, and BNIP3 genes and down-regulation of the PPARGC1B gene. These changes in the expression profile attest to activation of the metabolic cell reprogramming mechanisms aimed at reducing oxygen consumption by enabling the switch from aerobic to anaerobic glucose metabolism and the respective decrease in number of mitochondria. The possibility of practical use of the therapeutic properties of oxyquinoline derivatives is discussed.

Key Words

BeWo b30 placenta hypoxia oxyquinoline barrier 

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • E. N. Knyazev
    • 1
  • G. S. Zakharova
    • 1
  • L. A. Astakhova
    • 1
  • I. M. Tsypina
    • 1
    • 2
  • A. G. Tonevitsky
    • 1
    • 2
    Email author
  • G. T. Sukhikh
    • 3
  1. 1.BioClinicum Research CenterSolnaSweden
  2. 2.National Research University Higher School of EconomicsMoscowRussia
  3. 3.V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and PerinatologyMoscowRussia

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