CoCl-mimicked Hypoxia Induces the Assembly of Stress Granules in Trophoblast Cells eIF2α Phosphorylation-dependent and - Independent Pathways.

INTRODUCTION

Hypoxia has been implicated in preeclampsia (PE) pathophysiology. Stress granules (SGs) are present in the placenta of patients with PE. However, the pathways that contribute to SG aggregation in PE remain poorly understood.

OBJECTIVE

The objective of the current study is to investigate this issue.

METHODS

We first established an in vitro hypoxia model using human trophoblast cell line HTR-8/SVneo treated with cobalt chloride (CoCl). CCK8 assay and wound healing assay were conducted to assess the viability and migration of HTR-8/SVneo cells after exposure to CoCl-mimicked hypoxia. SG component expression in HTR-8/SVneo cells treated with CoCl alone, or in combination with indicated siRNAs was evaluated by reverse transcription quantitative PCR (RT-qPCR), western blot and immunofluorescence staining.

RESULTS

Our results found CoCl-mimicked hypoxia inhibits the proliferation and migration of HTR-8/SVneo cells. The treatment of CoCl can induce SG assembly in HTR-8/Svneo cells. Mechanistically, both heme-regulated inhibitors (HRI) mediated eukaryotic translation initiation factor (eIF)2α phosphorylation pathway and 4E binding protein 1 (4EBP1) pathway are involved in SG formation under the stress of CoCl- mimicked hypoxia.

CONCLUSION

Hypoxia-induced SGs in trophoblast cells might contribute to the etiology of PE.