scholarly journals Spermidine Attenuates Oxidative Stress-Induced Apoptosis via Blocking Ca2+ Overload in Retinal Pigment Epithelial Cells Independently of ROS

2021 ◽  
Vol 22 (3) ◽  
pp. 1361
Author(s):  
Da Hye Kim ◽  
Jeong-Hwan Kim ◽  
Hyun Hwangbo ◽  
So Young Kim ◽  
Seon Yeong Ji ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Antioxidant Properties ◽  
Retinal Pigment Epithelial Cells ◽  
Cellular Damage ◽  
Mitochondrial Activity ◽  
Rpe Cells ◽  
Pigment Epithelial ◽  
Human Rpe Cells

Retinal pigment epithelial (RPE) cells occupy the outer layer of the retina and perform various biological functions. Oxidative damage to RPE cells is a major risk factor for retinal degeneration that ultimately leads to vision loss. In this study, we investigated the role of spermidine in a hydrogen peroxide (H2O2)-induced oxidative stress model using human RPE cells. Our findings showed that 300 μM H2O2 increased cytotoxicity, apoptosis, and cell cycle arrest in the G2/M phase, whereas these effects were markedly suppressed by 10 μM spermidine. Furthermore, spermidine significantly reduced H2O2-induced mitochondrial dysfunction including mitochondrial membrane potential and mitochondrial activity. Although spermidine displays antioxidant properties, the generation of intracellular reactive oxygen species (ROS) upon H2O2 insult was not regulated by spermidine. Spermidine did suppress the increase in cytosolic Ca2+ levels resulting from endoplasmic reticulum stress in H2O2-stimulated human RPE cells. Treatment with a cytosolic Ca2+ chelator markedly reversed H2O2-induced cellular dysfunction. Overall, spermidine protected against H2O2-induced cellular damage by blocking the increase of intracellular Ca2+ independently of ROS. These results suggest that spermidine protects RPE cells from oxidative stress, which could be a useful treatment for retinal diseases.

The Protective Effect of Genipin on Oxidative Stress Under Hypoxia and Hyperglycemia in Retinal Pigment Epithelial Cells

2021 ◽  
Vol 11 (11) ◽  
pp. 2239-2245
Author(s):  
Daifeng Wu ◽  
Yulin Wang ◽  
Yueyang Wu ◽  
Shujuan Ding
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Cell Viability ◽  
Retinal Pigment Epithelial ◽  
Nuclear Translocation ◽  
Retinal Pigment ◽  
Pi3k Inhibitor ◽  
Retinal Pigment Epithelial Cells ◽  
Rpe Cells ◽  
Pigment Epithelial

We aimed to explore the protective effect of genipin on retinal pigment epithelial (RPE) cells under hypoxia and hyperglycemia. RPE cells were cultured under hyperglycemia and hypoxia mimicking agent DFX. The cells were then exposed to genipin (10–50 μM), genipin + phospha-tidylinositol (3,4,5) trisphosphates (PIP3) as phosphoinositide 3-kinase (PI3K) inhibitor, and genipin+ PI3K agonist, followed by CCK-8 assay to detect the cell viability. Western blot determined PI3K/protein kinase B (AKT) pathway, and apoptosis- and anti-apoptosis-related proteins levels. MitoSOXTM Red kit was conducted to analyze reactive oxygen species (ROS) content. Finally, confocal immunofluorescence staining assessed nuclear translocation of Nuclear factor erythroid-derived 2-like 2 (Nrf2). Hyperglycemia and hypoxia treatment induced injury in RPE cells, with nuclear translocation of Nrf2 and ROS production. Importantly, administration of genipin alleviated the injury, up-regulated Bcl-2 expression, inhibited caspase-3 activity and nuclear translocation of Nrf2, and down-regulated the level of Bax and ROS. In addition, genipin pretreatment obviously increased PI3K and Akt phosphorylation and promoted cell proliferation and viability. On the contrary, PI3K inhibitor inactivated PI3K/AKT and decreased cell viability while PI3K agonist showed the opposite effect. Genipin prevented oxidative stress and apoptosis induced by hyperglycemia and hypoxia through PI3K/Akt signaling pathway.

scholarly journals CFH exerts anti-oxidant effects on retinal pigment epithelial cells independently from protecting against membrane attack complex

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Céline Borras ◽  
Jérémie Canonica ◽  
Sylvie Jorieux ◽  
Toufik Abache ◽  
Mohamed El Sanharawi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Epithelial Cells ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Membrane Attack Complex ◽  
Retinal Pigment Epithelial Cells ◽  
Rpe Cells ◽  
Pigment Epithelial ◽  
Pigment Epithelial Cells

Abstract Age Related Macular Degeneration (AMD) is the first cause of social blindness in people aged over 65 leading to atrophy of retinal pigment epithelial cells (RPE), photoreceptors and choroids, eventually associated with choroidal neovascularization. Accumulation of undigested cellular debris within RPE cells or under the RPE (Drusen), oxidative stress and inflammatory mediators contribute to the RPE cell death. The major risk to develop AMD is the Y402H polymorphism of complement factor H (CFH). CFH interacting with oxidized phospholipids on the RPE membrane modulates the functions of these cells, but the exact role of CFH in RPE cell death and survival remain poorly understood. The aim of this study was to analyze the potential protective mechanism of CFH on RPE cells submitted to oxidative stress. Upon exposure to oxidized lipids 4-HNE (4-hydroxy-2-nonenal) derived from photoreceptors, both the human RPE cell line ARPE-19 and RPE cells derived from human induced pluripotent stem cells were protected from death only in the presence of the full length human recombinant CFH in the culture medium. This protective effect was independent from the membrane attack complex (MAC) formation. CFH maintained RPE cells tight junctions’ structure and regulated the caspase dependent apoptosis process. These results demonstrated the CFH anti-oxidative stress functions independently of its capacity to inhibit MAC formation.

scholarly journals High glucose promotes the migration of retinal pigment epithelial cells through increased oxidative stress and PEDF expression

2016 ◽  
Vol 311 (3) ◽  
pp. C418-C436 ◽  
Author(s):  
Mitra Farnoodian ◽  
Caroline Halbach ◽  
Cassidy Slinger ◽  
Bikash R. Pattnaik ◽  
Christine M. Sorenson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Blood Retinal Barrier ◽  
Rpe Cells ◽  
Pigment Epithelial ◽  
Proliferation And Apoptosis ◽  
The Impact

Defects in the outer blood-retinal barrier have significant impact on the pathogenesis of diabetic retinopathy and macular edema. However, the detailed mechanisms involved remain largely unknown. This is, in part, attributed to the lack of suitable animal and cell culture models, including those of mouse origin. We recently reported a method for the culture of retinal pigment epithelial (RPE) cells from wild-type and transgenic mice. The RPE cells are responsible for maintaining the integrity of the outer blood-retinal barrier whose dysfunction during diabetes has a significant impact on vision. Here we determined the impact of high glucose on the function of RPE cells. We showed that high glucose conditions resulted in enhanced migration and increased the level of oxidative stress in RPE cells, but minimally impacted their rate of proliferation and apoptosis. High glucose also minimally affected the cell-matrix and cell-cell interactions of RPE cells. However, the expression of integrins and extracellular matrix proteins including pigment epithelium-derived factor (PEDF) were altered under high glucose conditions. Incubation of RPE cells with the antioxidant N-acetylcysteine under high glucose conditions restored normal migration and PEDF expression. These cells also exhibited increased nuclear localization of the antioxidant transcription factor Nrf2 and ZO-1, reduced levels of β-catenin and phagocytic activity, and minimal effect on production of vascular endothelial growth factor, inflammatory cytokines, and Akt, MAPK, and Src signaling pathways. Thus high glucose conditions promote RPE cell migration through increased oxidative stress and expression of PEDF without a significant effect on the rate of proliferation and apoptosis.

TAK1 is involved in the autophagy process in retinal pigment epithelial cells

2016 ◽  
Vol 94 (2) ◽  
pp. 188-196 ◽  
Author(s):  
Yaron A. Green ◽  
Keren Ben-Yaakov ◽  
Orit Adir ◽  
Ayala Pollack ◽  
Zeev Dvashi
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment Epithelial ◽  
Transforming Growth Factor ◽  
Retinal Pigment ◽  
Specific Inhibitor ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Pigment Epithelial ◽  
Age Related

Autophagy is an evolutionarily conserved mechanism for degrading long-lived or malfunctioning proteins and organelles, such as those resulting from oxidative stress. Several publications have demonstrated the importance of the autophagy process in the pathophysiology of dry age-related macular degeneration (AMD). Still, the mechanism underlying this process and its involvement in dry AMD are not fully characterized. Investigating the autophagy process in retinal pigment epithelial (RPE) cells, we identified transforming growth factor β activated kinase 1 (TAK1) as a key player in the process. We found increased TAK1 phosphorylation in ARPE-19 and D407 cells treated with different inducers of autophagy, such as oxidative stress and rapamycin. Moreover, utilizing TAK1 specific inhibitor prior to oxidative stress or rapamycin treatment, we found significant reduction in LC3A/B-II expression. These results point at the involvement of TAK1 in the regulation of autophagy in RPE cells. This study suggests that aberrant activity of this kinase impairs autophagy and subsequently leads to alterations in the vitality of RPE cells. Proper activity of TAK1 may be essential for efficient autophagy, and crucial for the ability of RPE cells to respond to stress and dispose of damaged organelles, thus preventing or delaying retinal pathologies.

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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