MIND4-17 protects retinal pigment epithelium cells and retinal ganglion cells from UV.

Citation data:

Oncotarget, ISSN: 1949-2553, Vol: 8, Issue: 52, Page: 89793-89801

Publication Year:
2017
Captures 12
Readers 12
Citations 4
Citation Indexes 4
PMID:
29163788; 26883112
DOI:
10.18632/oncotarget.21131; 10.18632/oncotarget.7373
PMCID:
PMC4924696
Author(s):
Khammanivong, Ali; Sorenson, Brent S; Ross, Karen F; Dickerson, Erin B; Hasina, Rifat; Lingen, Mark W; Herzberg, Mark C
Publisher(s):
Impact Journals, LLC
Tags:
Medicine
article description
Nrf2 activation would efficiently protect retinal cells from UV radiation (UVR). Recent studies have developed a Nrf2-targeting thiazole-containing compound MIND4-17, which activates Nrf2 through blocking its association with Keap1. In the current study, we demonstrated that pretreatment with MIND4-17 efficiently protected retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs) from UVR. UVR-induced apoptosis in the retinal cells was also largely attenuated by MIND4-17 pretreatment. MIND4-17 presumably separated Nrf2 from Keap1, allowing its stabilization and accumulation in retinal cells, which then translocated to cell nuclei and promoted transcription of ARE-dependent anti-oxidant genes, including , and . Significantly, shRNA-mediated knockdown of Nrf2 almost completely abolished MIND4-17-induced cytoprotection against UVR. Further studies showed that MIND4-17 largely ameliorated UVR-induced ROS production, lipid peroxidation and DNA damages in RPEs and RGCs. Together, MIND4-17 protects retinal cells from UVR by activating Nrf2 signaling.