Transcriptional Regulation of Activating Transcription Factor 4 under Oxidative Stress in Retinal Pigment Epithelial ARPE-19/HPV-16 Cells

2011 ◽  
Vol 52 (3) ◽  
pp. 1226 ◽  
Author(s):  
Naoya Miyamoto ◽  
Hiroto Izumi ◽  
Rie Miyamoto ◽  
Han Bin ◽  
Hiroyuki Kondo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Hpv 16 ◽  
Pigment Epithelial ◽  
Activating Transcription Factor 4 ◽  
Activating Transcription Factor ◽  
Transcription Factor 4

scholarly journals Role of Activating Transcription Factor 4 in Murine Choroidal Neovascularization Model

2021 ◽  
Vol 22 (16) ◽  
pp. 8890
Author(s):  
Hiroto Yasuda ◽  
Miruto Tanaka ◽  
Anri Nishinaka ◽  
Shinsuke Nakamura ◽  
Masamitsu Shimazawa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Er Stress ◽  
Choroidal Neovascularization ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Activating Transcription Factor 4 ◽  
Age Related ◽  
Activating Transcription Factor ◽  
Transcription Factor 4

Neovascular age-related macular degeneration (nAMD) featuring choroidal neovascularization (CNV) is the principal cause of irreversible blindness in elderly people in the world. Integrated stress response (ISR) is one of the intracellular signals to be adapted to various stress conditions including endoplasmic reticulum (ER) stress. ISR signaling results in the upregulation of activating transcription factor 4 (ATF4), which is a mediator of ISR. Although recent studies have suggested ISR contributes to the progression of some age-related disorders, the effects of ATF4 on the development of CNV remain unclear. Here, we performed a murine model of laser-induced CNV and found that ATF4 was highly expressed in endothelial cells of the blood vessels of the CNV lesion site. Exposure to integrated stress inhibitor (ISRIB) reduced CNV formation, vascular leakage, and the upregulation of vascular endothelial growth factor (VEGF) in retinal pigment epithelium (RPE)-choroid-sclera complex. In human retinal microvascular endothelial cells (HRMECs), ISRIB reduced the level of ATF4 and VEGF induced by an ER stress inducer, thapsigargin, and recombinant human VEGF. Moreover, ISRIB decreased the VEGF-induced cell proliferation and migration of HRMECs. Collectively, our findings showed that pro-angiogenic effects of ATF4 in endothelial cells may be a potentially therapeutic target for patients with nAMD.

scholarly journals Sulforaphane Enhances the Ability of Human Retinal Pigment Epithelial Cell against Oxidative Stress, and Its Effect on Gene Expression Profile Evaluated by Microarray Analysis

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Liang Ye ◽  
Ting Yu ◽  
Yanqun Li ◽  
Bingni Chen ◽  
Jinshun Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Microarray Analysis ◽  
Retinal Pigment Epithelial ◽  
Nuclear Translocation ◽  
Retinal Pigment ◽  
Regulation Of Gene Expression ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Pigment Epithelial

To gain further insights into the molecular basis of Sulforaphane (SF) mediated retinal pigment epithelial (RPE) 19 cell against oxidative stress, we investigated the effects of SF on the regulation of gene expression on a global scale and tested whether SF can endow RPE cells with the ability to resist apoptosis. The data revealed that after exposure to H2O2, RPE 19 cell viability was increased in the cells pretreated with SF compared to the cell not treated with SF. Microarray analysis revealed significant changes in the expression of 69 genes in RPE 19 cells after 6 hours of SF treatment. Based on the functional relevance, eight of the SF-responsive genes, that belong to antioxidant redox system, and inflammatory responsive factors were validated. The up-regulating translation of thioredoxin-1 (Trx1) and the nuclear translocation of Nuclear factor-like2 (Nrf2) were demonstrated by immunoblot analysis in SF treated RPE cells. Our data indicate that SF increases the ability of RPE 19 cell against oxidative stress through up-regulating antioxidative enzymes and down-regulating inflammatory mediators and chemokines. The results suggest that the antioxidant, SF, may be a valuable supplement for preventing and retarding the development of Age Related Macular Degeneration.

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