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

Chaopeng Li; Kang Yan; Wenqi Wang; Qing Bai; Changming Dai; Xiaofeng Li; Darui Huang

doi:10.18632/oncotarget.21131

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Research Papers:

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

Chaopeng Li, Kang Yan, Wenqi Wang, Qing Bai, Changming Dai _, Xiaofeng Li and Darui Huang

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Oncotarget. 2017; 8:89793-89801. https://doi.org/10.18632/oncotarget.21131

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Abstract

Chaopeng Li1,*, Kang Yan2,*, Wenqi Wang1, Qing Bai1, Changming Dai1, Xiaofeng Li1 and Darui Huang1

1Department of Ophthalmology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

2Department of Ultrasound, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

*These authors share co-first authorship

Correspondence to:

Changming Dai, email: [email protected]

Keywords: UV radiation, Nrf2, MIND4-17, retinal pigment epithelium cells, retinal ganglion cells

Received: August 18, 2017 Accepted: September 03, 2017 Published: September 21, 2017

ABSTRACT

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 HO1, NQO1 and GCLM. 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.

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Research Papers:

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

Abstract