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Neuroligin-3 protects retinal cells from H2O2-induced cell death via activation of Nrf2 signaling

Author:
Li, Xiu-miao, Huang, Dan, Yu, Qing, Yang, Jian, Yao, Jin
Source:
Biochemical and biophysical research communications 2018 v.502 no.1 pp. 166-172
ISSN:
0006-291X
Subject:
DNA damage, apoptosis, enzymes, epithelium, ganglia, gene expression, humans, hydrogen peroxide, lipid peroxidation, messenger RNA, oxidative stress, retina
Abstract:
Intensified oxidative stress can cause severe damage to human retinal pigment epithelium (RPE) cells and retinal ganglion cells (RGCs). The potential effect of neuroligin-3 (NLGN3) against the process is studied here. Our results show that NLGN3 efficiently inhibited hydrogen peroxide (H2O2)-induced death and apoptosis in human RPE cells and RGCs. H2O2-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage in retinal cells were alleviated by NLGN3. NLGN3 activated nuclear-factor-E2-related factor 2 (Nrf2) signaling, enabling Nrf2 protein stabilization, nuclear translocation and expression of key anti-oxidant enzymes (HO1, NOQ1 and GCLC) in RPE cells and RGCs. Further results demonstrate that NLGN3 activated Akt-mTORC1 signaling in retinal cells. Conversely, Akt-mTORC1 inhibitors (RAD001 and LY294002) reduced NLGN3-induced HO1, NOQ1 and GCLC mRNA expression. Significantly, Nrf2 silencing by targeted shRNAs reversed NLGN3-induced retinal cytoprotection against H2O2. We conclude that NLGN3 activates Nrf2 signaling to protect human retinal cells from H2O2. NLGN3 could be further tested as a valuable retinal protection agent.
Agid:
5969839