Metabolic Reprogramming of Trophoblast Cells in Response to Hypoxia

E N Knyazev; G S Zakharova; L A Astakhova; I M Tsypina; A G Tonevitsky; G T Sukhikh

doi:10.1007/s10517-019-04342-1

Metabolic Reprogramming of Trophoblast Cells in Response to Hypoxia

Bull Exp Biol Med. 2019 Jan;166(3):321-325. doi: 10.1007/s10517-019-04342-1. Epub 2019 Jan 9.

Authors

E N Knyazev¹, G S Zakharova¹, L A Astakhova¹, I M Tsypina^{1

2}, A G Tonevitsky^{3

4}, G T Sukhikh⁵

Affiliations

¹ BioClinicum Research Center, Solna, Sweden.
² National Research University Higher School of Economics, Moscow, Russia.
³ BioClinicum Research Center, Solna, Sweden. [email protected].
⁴ National Research University Higher School of Economics, Moscow, Russia. [email protected].
⁵ V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Moscow, Russia.

PMID: 30627907
DOI: 10.1007/s10517-019-04342-1

Abstract

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.

Keywords: BeWo b30; barrier; hypoxia; oxyquinoline; placenta.

MeSH terms

Carrier Proteins / antagonists & inhibitors
Carrier Proteins / genetics*
Carrier Proteins / metabolism
Cell Hypoxia / genetics
Cell Line, Tumor
Cellular Reprogramming
Female
Gene Expression Profiling
Gene Expression Regulation
Glycolysis / drug effects
Glycolysis / genetics
Humans
Membrane Proteins / agonists
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Models, Biological
Nitric Oxide Synthase Type III / genetics*
Nitric Oxide Synthase Type III / metabolism
Oxidative Phosphorylation / drug effects
Oxyquinoline / pharmacology*
Pre-Eclampsia / genetics
Pre-Eclampsia / metabolism
Pre-Eclampsia / pathology
Pregnancy
Protein Serine-Threonine Kinases / genetics*
Protein Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins / agonists
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins / metabolism
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
RNA-Binding Proteins
Trophoblasts / drug effects*
Trophoblasts / metabolism
Trophoblasts / pathology

Substances

BNIP3 protein, human
Carrier Proteins
Membrane Proteins
PDK1 protein, human
PPARGC1B protein, human
Proto-Oncogene Proteins
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
RNA-Binding Proteins
Oxyquinoline
NOS3 protein, human
Nitric Oxide Synthase Type III
Protein Serine-Threonine Kinases