Knyazev E N, Zakharova G S, Astakhova L A, Tsypina I M, Tonevitsky A G, Sukhikh G T
BioClinicum Research Center, Solna, Sweden.
National Research University Higher School of Economics, Moscow, Russia.
Bull Exp Biol Med. 2019 Jan;166(3):321-325. doi: 10.1007/s10517-019-04342-1. Epub 2019 Jan 9.
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.
滋养层细胞缺氧是胎盘正常发育的重要调节因素。然而，一些与缺氧相关的病理状态，如先兆子痫，会损害胎盘细胞的功能。氧喹啉衍生物通过稳定HIF-1转录复合体来抑制HIF-脯氨酰羟化酶，从而模拟细胞对缺氧的反应。在人绒毛膜癌细胞BeWo b30（滋养层模型）中，氧喹啉增加了核心缺氧反应基因的表达，同时上调了NOS3、PDK1和BNIP3基因，并下调了PPARGC1B基因。表达谱的这些变化证明了代谢细胞重编程机制的激活，该机制旨在通过使有氧葡萄糖代谢转变为无氧葡萄糖代谢以及线粒体数量相应减少来降低氧消耗。文中讨论了氧喹啉衍生物治疗特性的实际应用可能性。
