GRP75 Modulates Endoplasmic Reticulum-Mitochondria Coupling and Accelerates Ca²⁺-Dependent Endothelial Cell Apoptosis in Diabetic Retinopathy.

ABSTRACT: Endoplasmic reticulum (ER) and mitochondrial dysfunction play fundamental roles in the pathogenesis of diabetic retinopathy (DR). However, the interrelationship between the ER and mitochondria are poorly understood in DR. Here, we established high glucose (HG) or advanced glycosylation end products (AGE)-induced human retinal vascular endothelial cell (RMEC) models in vitro, as well as a streptozotocin (STZ)-induced DR rat model in vivo. Our data demonstrated that there was increased ER-mitochondria coupling in the RMECs, which was accompanied by elevated mitochondrial calcium ions (Ca²⁺) and mitochondrial dysfunction under HG or AGE incubation. Mechanistically, ER-mitochondria coupling was increased through activation of the IP3R1-GRP75-VDAC1 axis, which transferred Ca^2+</

SUBMITTER: Li Y 

PROVIDER: S-EPMC9776029 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature