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

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.

Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

“…In human glaucom TMCs, resveratrol has been reported to reduce the expression of proinflamm ER-related oxidative stress has been reported in both TMCs and RGCs in the context of glaucomatous optic neuropathy. Studies on TMCs have demonstrated the involvement of the PERK-eIF2α-ATF4-CHOP cascade in glaucomatous TM, both in human and murine cells, highlighting the activation of this pathway in glaucoma [245][246][247][248]. Similarly, various studies have described the implication of the PERK-eIF2α-ATF4-CHOP pathway in RGC loss [249][250][251][252].…”

Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

“…ER-related oxidative stress has been reported in both TMCs and RGCs in the context of glaucomatous optic neuropathy. Studies on TMCs have demonstrated the involvement of the PERK-eIF2α-ATF4-CHOP cascade in glaucomatous TM, both in human and murine cells, highlighting the activation of this pathway in glaucoma [252][253][254][255]. Similarly, various studies have described the implication of the PERK-eIF2α-ATF4-CHOP pathway in RGC loss [256][257][258][259].…”