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Метаболическое перепрограммирование трофобласта при моделировании ответа на гипоксию

Князев Е. Н., Захарова Г. С., Астахова Л. А., Цыпина И. М., Тоневицкий А. Г.

Hypoxia of trophoblast cells is an important regulating factor in the process of normal placenta development. However, the effect of hypoxia on the placenta in a number of pathological conditions, such as preeclampsia, leads to impaired cellular functions. A oxyquinoline derivative is capable of inhibiting HIF-prolyl hydroxylases, thereby stabilizing the transcription complex of HIF-1 and activating the cell response to hypoxia. BeWo b30 human choriocarcinoma cells are used to model trophoblast, which forms the basis for placenta barrier. Oxyquinoline effect leads both to an increased expression of a number of the genes that form the core response to hypoxia, and upregulated expression of NOS3, PDK1, and BNIP3 genes and downregulated expression of the PPARGC1B gene. This indicates the activation of mechanisms of metabolic cell reprogramming aimed at reducing oxygen consumption by reducing the number of mitochondria and switching from aerobic glucose metabolism to anaerobic. Possible applications of the obtained results is under discussion.