Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal; I3S, Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.
Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal; CINTESIS, Center for Health Technology and Services Research, University of Porto, Porto, Portugal.
Eur J Pharmacol. 2018 Aug 15;833:16-24. doi: 10.1016/j.ejphar.2018.05.038. Epub 2018 May 25.
Our aim was to investigate the effect of two xenobiotics to which pregnant woman may be exposed, the drug of abuse ethanol (EtOH) (and its metabolite acetaldehyde (ACA)) and the therapeutic agent metformin (METF), on placentation-related processes in an extravillous trophoblastic (EVTs) cell line (HTR-8/SVneo cells). EtOH, ACA and METF (24 h) significantly reduced cell proliferation rates, culture growth, viability and migratory capacity of HTR-8/SVneo cells. Moreover, both EtOH (100 μM) and METF (1 mM) increased the apoptosis index and inhibited H-deoxy-D-glucose (H-DG) and H-folic acid (H-FA) uptake. mTOR, JNK and PI3K intracellular signaling pathways were involved in the effect of EtOH upon H-FA uptake and in the effect of METF upon cell viability, and mTOR and JNK in the effect of EtOH upon cell viability and H-DG uptake. We show that EtOH and METF have a detrimental effect in placentation-related processes of HTR-8/SVneo cells. Moreover, mTOR, JNK and PI3K appear to mediate some of these negative effects.
我们的目的是研究两种孕妇可能接触到的外源性物质对胎盘相关过程的影响，即药物滥用乙醇（EtOH）（及其代谢物乙醛（ACA））和治疗药物二甲双胍（METF）。在体外绒毛滋养层（EVTs）细胞系（HTR-8/SVneo 细胞）中，EtOH、ACA 和 METF（24 小时）显著降低了细胞增殖率、培养物生长、活力和迁移能力。此外，EtOH（100μM）和 METF（1mM）均增加了细胞凋亡指数，并抑制了 H-脱氧-D-葡萄糖（H-DG）和 H-叶酸（H-FA）摄取。mTOR、JNK 和 PI3K 细胞内信号通路参与了 EtOH 对 H-FA 摄取的影响以及 METF 对细胞活力的影响，并且 mTOR 和 JNK 参与了 EtOH 对细胞活力和 H-DG 摄取的影响。我们表明，EtOH 和 METF 对 HTR-8/SVneo 细胞的胎盘相关过程有不良影响。此外，mTOR、JNK 和 PI3K 似乎介导了其中一些负面效应。
