The role of GRP78 in oxidative stress induced by tunicamycin in trabecular meshwork cells

  • Fang Chai 1Department of Ophthalmology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; 2Department of Ophthalmology, Xi’an People’s Hospital (Xi’an Fourth Hospital), Shaanxi Eye Hospital, Affiliated Guangren Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710004, China
  • Hong Yan Department of Ophthalmology, Xi’an People’s Hospital (Xi’an Fourth Hospital), Shaanxi Eye Hospital, Affiliated Guangren Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710004, China
  • Xiquan Zhao Department of Ophthalmology, Xi’an People’s Hospital (Xi’an Fourth Hospital), Shaanxi Eye Hospital, Affiliated Guangren Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710004, China
  • Juan Li Department of Ophthalmology, Xi’an People’s Hospital (Xi’an Fourth Hospital), Shaanxi Eye Hospital, Affiliated Guangren Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710004, China
  • Cheng Pei Department of Ophthalmology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China

Abstract

Objective: To clarify the regulatory effect of GRP-78 induced by tunicamycin on endoplasmic reticulum (ER) stress. Methods: Tunicamycin was used to induce ER stress in trabecular meshwork cells (HTMC and GTM3). Cell apoptosis and ROS content were detected by flow cytometry to reveal the effect of tunicamycin on trabecular meshwork cells. Results: Tunicamycin could significantly increase the ROS content and the apoptosis rate in HTMC and GTM3 (p<0.01). The results showed that tunicamycin could increase the Ca2+ flow in cells. Tunicamycin can also increase expression levels of GRP78,VDAC1, ATF4, PERK, eIF2a, and CHOP (p<0.01). Overexpression of GRP78 protected cells from ER stress. Co-IP test showed that GRP78 directly bound to eIF2. These results suggest that GRP78 may play a regulatory role by regulating eIF2. Conclusion: Tunicamycin induces oxidative stress in trabecular meshwork cells, and the increase in GRP78 expression can protect the cells during ER stress by regulating eIF2.

Published
2022-03-02
Section
Articles