Knockdown of GCN2 inhibits high glucose-induced oxidative stress and apoptosis in retinal pigment epithelial cells.

Abstract

Increasing evidence suggests that general control nonderepressible 2 (GCN2) is a critical regulator of oxidative stress and cell apoptosis in response to various stimuli. However, the role of GCN2 in diabetic retinopathy remains unclear. The aim of the present study was to investigate the effects of GCN2 on oxidative stress and apoptosis in ARPE-19 cells exposed to high glucose. The results showed that GCN2 was highly expressed in high glucose-induced ARPE-19 cells. Moreover, knockdown of GCN2 greatly improved ARPE-19 cell viability in response to high glucose. In addition, GCN2 knockdown significantly suppressed the production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased superoxide dismutase (SOD) activity in high glucose-stimulated ARPE-19 cells. Furthermore, GCN2 knockdown reduced cell apoptosis and enhanced the activation of nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway in high glucose-stimulated ARPE-19 cells. However, knockdown of Nrf2 reversed the effects of GCN2 on oxidative stress and cell apoptosis. Taken together, our findings suggest that knockdown of GCN2 inhibits high glucose-induced oxidative stress and apoptosis in ARPE-19 cells through activation of the Nrf2/HO-1 pathway.