Hypermethylation of endoplasmic reticulum disulfide oxidase 1α leads to trophoblast cell apoptosis through endoplasmic reticulum stress in preeclampsia

Research output: Contribution to journalArticle

Abstract

Abnormal trophoblast cell apoptosis is implicated in the pathogenesis of pregnancy-related disorders including preeclampsia (PE), and endoplasmic reticulum (ER) stress has been considered as a novel pathway in the regulation of cell apoptosis. In this study, we observed that both apoptosis and ER stress are triggered in trophoblast cells under hypoxia as well as in the placenta of PE rats. Quantitative polymerase chain reaction and Western blot analysis showed that the expression of endoplasmic reticulum disulfide oxidase 1α (ERO1α) is suppressed in trophoblast cells under hypoxia due to the hypermethylation of the ERO1α promoter region, and the inhibition of ERO1α expression plays an important role in ER stress and trophoblast cell apoptosis. Furthermore, we found that DNA methyltransferase 1 (DNMT1) is a key methyltransferase for DNA methylation in the regulation of ERO1α expression, and the binding level of DNMT1 to the ERO1α promoter is markedly elevated under hypoxia although DNMT1 expression is inhibited by hypoxia, suggesting that the binding level of DNMT1 to the ERO1α promoter region rather than the DNMT1 expression level contributes to the hypermethylation of ERO1α. Taken together, these results demonstrate that the hypermethylation of ERO1α mediated by increased binding of DNMT1 to the ERO1α promoter leads to trophoblast cell apoptosis through ER stress in the placenta of PE rats, which shed insight into the etiology of PE and might present a validated therapeutic target for the treatment of PE.

Details

Authors
  • Jiantuan Xiong
  • Ning Ding
  • Tingting Gao
  • Yanhua Wang
  • Wei Guo
  • Hui Zhang
  • Xiaoli Ma
  • Fan Li
  • Jianmin Sun
  • Xiaoling Yang
  • Kai Wu
  • Huiping Zhang
  • Yideng Jiang
Organisations
External organisations
  • Ningxia Medical University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
  • Cancer and Oncology

Keywords

  • Apoptosis, DNA methylation, DNA methyltransferase (DNMT), Endoplasmic reticulum (ER) stress, Endoplasmic reticulum oxidoreductin 1α (ERO1α)
Original languageEnglish
Pages (from-to)8588-8599
JournalJournal of Cellular Biochemistry
Volume119
Issue number10
Early online date2018 Jul 30
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes