scholarly journals PRMT1 and PRMT4 Regulate Oxidative Stress-Induced Retinal Pigment Epithelial Cell Damage in SIRT1-Dependent and SIRT1-Independent Manners

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Dong-Il Kim ◽  
Min-Jung Park ◽  
Joo-Hee Choi ◽  
In-Seon Kim ◽  
Ho-Jae Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Retinal Pigment Epithelial ◽  
Cell Damage ◽  
Retinal Pigment ◽  
Arginine Methylation ◽  
Type I ◽  
Dependent Manner ◽  
Sirt1 Expression ◽  
Pigment Epithelial

Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is involved in the progression of diabetic retinopathy. Arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) has emerged as an important histone modification involved in diverse diseases. Sirtuin (SIRT1) is a protein deacetylase implicated in the onset of metabolic diseases. Therefore, we examined the roles of type I PRMTs and their relationship with SIRT1 in human RPE cells under H2O2-induced oxidative stress. H2O2treatment increased PRMT1 and PRMT4 expression but decreased SIRT1 expression. Similar to H2O2treatment, PRMT1 or PRMT4 overexpression increased RPE cell damage. Moreover, the H2O2-induced RPE cell damage was attenuated by PRMT1 or PRMT4 knockdown and SIRT1 overexpression. In this study, we revealed that SIRT1 expression was regulated by PRMT1 but not by PRMT4. Finally, we found that PRMT1 and PRMT4 expression is increased in the RPE layer of streptozotocin-treated rats. Taken together, we demonstrated that oxidative stress induces apoptosis both via PRMT1 in a SIRT1-dependent manner and via PRMT4 in a SIRT1-independent manner. The inhibition of the expression of type I PRMTs, especially PRMT1 and PRMT4, and increased SIRT1 could be therapeutic approaches for diabetic retinopathy.

scholarly journals Protective effects of delphinidin against H2O2–induced oxidative injuries in human retinal pigment epithelial cells

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Timin Ni ◽  
Wanju Yang ◽  
Yiqiao Xing
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Ros Generation ◽  
Dependent Manner ◽  
Pigment Epithelial ◽  
Age Related

Abstract Age-related macular degeneration (AMD) is now one of the leading causes of blindness in the elderly population and oxidative stress-induced damage to retinal pigment epithelial (RPE) cells occurs as part of the pathogenesis of AMD. In the present study, we evaluated the protective effect of delphinidin (2-(3,4,5-trihydroxyphenyl) chromenylium-3,5,7-triol) against hydrogen peroxide (H2O2)-induced toxicity in human ARPE-19 cells and its molecular mechanism. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry demonstrated that pretreatment of ARPE-19 cells with delphinidin (25, 50, and 100 μg/ml) significantly increased cell viability and reduced the apoptosis from H2O2 (0.5 mM)-induced oxidative stress in a concentration-dependent manner, which was achieved by the inhibition of Bax, cytochrome c, and caspase-3 protein expression and enhancement of Bcl-2 protein. The same tendency was observed in ARPE-19 cells pre-treated with 15 mM of N-acetylcysteine (NAC) before the addition of H2O2. Furthermore, pre-incubation of ARPE-19 cells with delphinidin markedly inhibited the intracellular reactive oxygen species (ROS) generation and Nox1 protein expression induced by H2O2. Moreover, the decreased antioxidant enzymes activities of superoxide dismutase (SOD), catalase (CAT), and glutathione-peroxidase (GSH-PX) and elevated (MDA) level in H2O2-treated cells were reversed to the normal standard by the addition of delphinidin, which was regulated by increasing nuclear Nrf2 protein expression in ARPE-19 cells. Our results suggest that delphinidin effectively protects human ARPE-19 cells from H2O2-induced oxidative damage via anti-apoptotic and antioxidant effects.

Changes in Mitochondrial Morphology and Mitochondrial Fission/Fusion Gene Expression in Retinal Pigment Epithelial Cells During Oxidative Stress

2020 ◽  
Vol 12 (10) ◽  
pp. 1192-1199
Author(s):  
Zhi Ji ◽  
Xu Liu ◽  
Xia Wang ◽  
Yuan Ren ◽  
Ying Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Retinal Pigment Epithelial ◽  
Fusion Gene ◽  
Cell Damage ◽  
Retinal Pigment ◽  
Mitochondrial Morphology ◽  
Pigment Epithelial

Age-related macular degeneration (AMD) represents a serious impairment for the elderly. Because the pathogenesis of AMD has not been completely defined, the available therapeutic treatments are not ideal. Retinal pigment epithelial (RPE) cells are essential for photoreceptor cell maintenance and survival; however, the mechanisms underlying RPE cell damage and AMD remains to be elucidated. It is known that abnormal mitochondrial gene expression causes mitochondrial dysfunction, induces cell damage, and results in disease. In this study, ARPE-19 cells were treated with different concentrations of H2O2. It was found that excessive H2O2 concentration resulted in significant contraction of ARPE-19 cells and increased cell death, and destruction of mitochondrial structure as well as membrane and crest. RT-PCR results showed that decreased expression of the Fis1 gene was evident in H2O2-treated cells. There were no significant differences observed among the different H2O2 concentration groups. The expression of the fission genes, MTP18 and Dnmp1, and the fusion genes, Mnf1 and Mnf2, was not significantly different. Real-time PCR results revealed that the expression of the Fis1 gene decreased concomitantly with different concentrations of H2O2, whereas the expression of the Mfn2 gene increased by treatment with 200 μMH2O2. There were no significant differences in the expression of the other genes. These results indicate that abnormal expression of the mitochondrial Fis1 fission gene, and the Mfn2 fusion gene caused mitochondrial dysfunction in ARPE-19 cells. This indicates that the imbalance of mitochondrial dynamics may contribute to cell death in an oxidative stress environment.

scholarly journals Sauchinone inhibits high glucose-induced oxidative stress and apoptosis in retinal pigment epithelial cells

RSC Advances ◽  
2019 ◽  
Vol 9 (30) ◽  
pp. 17065-17071
Author(s):  
Yang Shi ◽  
Yongzhou Zhang ◽  
Yan Li ◽  
Chenjun Tong
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Common Complication ◽  
Pigment Epithelial ◽  
Working Age ◽  
Pigment Epithelial Cells

Diabetic retinopathy (DR) is a common complication of diabetes mellitus and results in acquired blindness among working-age adults.

scholarly journals Sulforaphane Alleviates Particulate Matter-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Hyunchae Sim ◽  
Wonhwa Lee ◽  
Samyeol Choo ◽  
Eui Kyun Park ◽  
Moon-Chang Baek ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Particulate Matter ◽  
Oxidative Damage ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Dependent Manner ◽  
Rpe Cells ◽  
Pigment Epithelial ◽  
Dose Dependent ◽  
Antioxidant Effects

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly, and oxidative damage to retinal pigment epithelial (RPE) cells plays a major role in the pathogenesis of AMD. Exposure to high levels of atmospheric particulate matter (PM) with an aerodynamic diameter of <2.5 μm (PM2.5) causes respiratory injury, primarily due to oxidative stress. Recently, a large community-based cohort study in the UK reported a positive correlation between PM2.5 exposure and AMD. Sulforaphane (SFN), a natural isothiocyanate found in cruciferous vegetables, has known antioxidant effects. However, the protective effects of SNF in the eye, especially in the context of AMD, have not been evaluated. In the present study, we evaluated the effect of SFN against PM2.5-induced toxicity in human RPE cells (ARPE-19) and elucidated the molecular mechanism of action. Exposure to PM2.5 decreased cell viability in ARPE-19 cells in a time- and dose-dependent manner, potentially due to elevated intracellular reactive oxygen species (ROS). SFN treatment increased ARPE-19 cell viability and decreased PM2.5-induced oxidative stress in a dose-dependent manner. PM2.5-induced downregulation of serum- and glucocorticoid-inducible kinase 1 (SGK1), a cell survival factor, was recovered by SFN. PM2.5 treatment decreased the enzymatic activities of the antioxidant enzymes including superoxide dismutase and catalase, which were restored by SFN treatment. Taken together, these findings suggest that SFN effectively alleviates PM2.5-induced oxidative damage in human ARPE-19 cells via its antioxidant effects, and that SFN can potentially be used as a therapeutic agent for AMD, particularly in cases related to PM2.5 exposure.

scholarly journals Casein Kinase 2-Interacting Protein-1 Alleviates High Glucose-Reduced Autophagy, Oxidative Stress, and Apoptosis in Retinal Pigment Epithelial Cells via Activating the p62/KEAP1/NRF2 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xia Zhao ◽  
Jing Wang ◽  
Pei Li ◽  
Liying Tang ◽  
Yuzhi Bai
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
High Glucose ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Interacting Protein ◽  
Rpe Cells ◽  
Pigment Epithelial

Background. Casein kinase 2-interacting protein-1 (CKIP-1) has been proved to be associated with complications of diabetes. Diabetic retinopathy is a main diabetic complication which usually leads to blindness. The current study aims to investigate the role of CKIP-1 in high glucose-treated retinal pigment epithelial (RPE) cells which is a component of blood-retinal barriers. Methods. The RPE cells, ARPE-19, are treated with high glucose to mimic the diabetic stimulation. CKIP-1 was overexpressed in ARPE-19 cells to evaluate its effects on autophagy, oxidative stress, and apoptosis induced by high glucose treatment, using Western blot, immunofluorescence, and flow cytometry assays, respectively. Results. CKIP-1 was expressed at a lower level in high glucose-treated cells than in normal glucose cells. Overexpression of CKIP-1 enhanced the Nrf2 translocation to the nucleus. Furthermore, high glucose-induced autophagy, oxidative stress, and apoptosis were inhibited after overexpression of CKIP-1. Also, CKIP-1 regulates the p62/Keap1/Nrf2 signaling, which might be the potential mechanism in this model. Conclusion. In conclusion, CKIP-1 may be a potential therapeutic target that protects RPE cells from injury and subsequent diabetic retinopathy induced by high glucose.

scholarly journals Relative Contribution of Different Mitochondrial Oxidative Phosphorylation Components to the Retinal Pigment Epithelium Barrier Function: Implications for RPE-Related Retinal Diseases

2021 ◽  
Vol 22 (15) ◽  
pp. 8130
Author(s):  
Michael H. Guerra ◽  
Thangal Yumnamcha ◽  
Lalit P. Singh ◽  
Ahmed S. Ibrahim
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Barrier Function ◽  
Complex I ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Diseases ◽  
Dependent Manner ◽  
Pigment Epithelial ◽  
Dose Dependent

Disruption of retinal pigment epithelial (RPE) barrier integrity is involved in the pathology of several blinding retinal diseases including age-related macular degeneration (AMD) and diabetic retinopathy (DR), but the underlying causes and pathophysiology are not completely well-defined. Mitochondria dysfunction has often been considered as a potential candidate implicated in such a process. In this study, we aimed to dissect the role of different mitochondrial components; specifically, those of oxidative phosphorylation (OxPhos), in maintaining the barrier functionality of RPE. Electric cell-substrate impedance sensing (ECIS) technology was used to collect multi-frequency electrical impedance data to assess in real-time the barrier formation of the RPE cells. For this purpose, the human retinal pigment epithelial cell line—ARPE-19—was used and treated with varying concentrations of specific mitochondrial inhibitors that target different steps in OxPhos: Rotenone for complex I (the largest protein complex in the electron transport chain (ETC)); oligomycin for ATP synthase; and carbonyl cyanide-p-trifluoromethoxyphenyl hydrazone (FCCP) for uncoupling ATP synthesis from the accompanying ETC. Furthermore, data were modeled using the ECIS-Zθ software to investigate in depth the effects of these inhibitors on three separate barrier parameters: cell–cell interactions (Rb), cell–matrix interactions (α), and the cell membrane capacitance (Cm). The viability of ARPE-19 cells was determined by lactate dehydrogenase (LDH) Cytotoxicity Assay. The ECIS program’s modeling demonstrated that FCCP and thus OxPhos uncoupling disrupt the barrier function in the ARPE-19 cells across all three components of the total resistance (Rb, α, and Cm) in a dose-dependent manner. On the other hand, oligomycin and thus ATP synthase inhibition mostly affects the ARPE-19 cells' attachment to their substrate evident by a significant decrease in α resistance in a dose-dependent manner, both at the end and throughout the duration of the experiment. On the contrary, rotenone and complex I inhibition mostly affect the ARPE-19 paracellular resistance Rb in a dose-dependent manner compared to basolateral resistance α or Cm. Our results clearly demonstrate differential roles for different mitochondrial components in maintaining RPE cell functionality in which uncoupling of OxPhos is a major contributing factor to the disruption barrier function. Such differences can be used in investigating gene expression as well as for screening of selective agents that improve the OxPhos coupling efficiency to be used in the therapeutic approach for treating RPE-related retinal diseases.

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