scholarly journals PRDX6 Protects ARPE-19 Cells from Oxidative Damage via PI3K/AKT Signaling

2015 ◽  
Vol 36 (6) ◽  
pp. 2217-2228 ◽  
Author(s):  
Xu Zha ◽  
Guojiu Wu ◽  
Xueying Zhao ◽  
Liqiong Zhou ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Blue Light ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Annexin V ◽  
Retinal Disease ◽  
Akt Signaling ◽  
The Body ◽  
H2o2 Treatment

Background/Aims: Oxidative stress that damages cells of the retinal pigment epithelium (RPE) can cause the development of hereditary retinal disease (HRD). PRDX6, which is a member of the PRDX family, is essential for removing metabolic free radicals from the body. However, the effect of PRDX6 on oxidative stress in HRD remains unknown. In this study, we sought to investigate the role of PRDX6 in oxidative stress-induced HRD in ARPE-19 cells and the molecular mechanism involved. Methods: ARPE-19 cells were used in the current study. Intracellular ROS levels were determined by flow cytometry. Lipid peroxidation was measured using a commercial MDA assay kit. Cellular variability was determined by MTT assay. Apoptosis was determined using an Annexin V-FITC Apoptosis Detection Kit. mRNA and protein expression levels were detected by real-time PCR and western blot analysis, respectively. Results: We found that H2O2 and blue light could induce significant oxidative stress damage and cell death in ARPE-19 cells. Furthermore, we found that PRDX6 levels significantly decreased after H2O2 treatment. PRDX6 overexpression protected ARPE-19 cells from H2O2- and blue light-induced oxidative damage, while PRDX6 knockdown enhanced oxidative damage in these cells. Mechanistically, we found that PRDX6 prevented oxidative damage and promoted ARPE-19 cell survival through the PI3K/AKT signaling pathway. Conclusions: Collectively, these results suggest that PRDX6 protects ARPE-19 cells from H2O2-induced oxidative stress and apoptosis and that this protection is mediated at least partially through the PI3K/AKT pathway.

scholarly journals Oxidative stress alters transcript localization of disease-causing genes in the retinal pigment epithelium

2021 ◽  
Author(s):  
Tadeusz J Kaczynski ◽  
Elizabeth D Au ◽  
Michael H Farkas
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Induced Pluripotent Stem Cell ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Nuclear Retention ◽  
Age Related

Nuclear retention is a mechanism whereby RNA transcripts are held in the nucleus to maintain a proper nuclear-to-cytoplasmic balance or as a stockpile for use in responding to stimuli. Many mechanisms are employed to determine whether transcripts are retained or exported to the cytoplasm, though the extent to which tissue- or cell-type, stressors, or disease pathogenesis affect this process remains unclear. As the most biochemically active tissue in the body, the retina must mitigate endogenous and exogenous stressors to maintain cell health and tissue function. Oxidative stress, believed to contribute to the pathogenesis, or progression, of age-related macular degeneration (AMD) and inherited retinal dystrophies (IRDs), is produced both internally from biochemical processes, as well as externally from environmental insult. To evaluate the effect of oxidative stress on transcript localization in the retinal pigment epithelium (RPE), we performed poly-A RNA sequencing on nuclear and cytoplasmic fractions from induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE) cells exposed to hydrogen peroxide, as well as untreated controls. Under normal conditions, the number of mRNA transcripts retained in the nucleus exceeded that found in studies of other tissues. Further, the nuclear-to-cytoplasmic ratio of transcripts is altered following oxidative stress, as is the retention of genes associated with AMD, IRDs, and those important for RPE physiology. These results provide a retention catalog of all expressed mRNA in iPSC-RPE under normal conditions and after exposure to hydrogen peroxide, offering insight into one of the potential roles oxidative stress plays in the progression of visual disorders.

scholarly journals Differential Mechanisms of Action and Efficacy of Vitamin E Components in Antioxidant Cytoprotection of Human Retinal Pigment Epithelium

2022 ◽  
Vol 12 ◽  
Author(s):  
R. Scott Duncan ◽  
Daniel T. Hurtado ◽  
Conner W. Hall ◽  
Peter Koulen
Keyword(s):  
Oxidative Stress ◽  
Vitamin E ◽  
Retinal Pigment Epithelium ◽  
Oxidative Damage ◽  
Mechanism Of Action ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Similar Efficacy ◽  
Rpe Cells ◽  
Junction Protein

The purpose of this study was to determine if different vitamin E components exhibit similar efficacy and mechanism of action in protecting Retinal pigment epithelium (RPE) cells from oxidative damage. We hypothesized that α-tocopherol (αT) is unique among vitamin E components in its cytoprotective mechanism of action against oxidative stress in RPE cells and that it requires protein synthesis for optimal antioxidant effect. We used cell viability assays, fluorescent chemical labeling of DNA and actin and immuno-labeling of the antioxidant proteins Nrf2 and Sod2 and of the tight junction protein, ZO-1, and confocal microscopy to determine the effects of αT and γT against oxidative stress in immortalized human RPE cells (hTERT-RPE). Using the four main vitamin E components, αT, γT, δ-tocopherol (δT) and α-tocotrienol (αTr), we ascertained that they exhibit similar, but not identical, antioxidant activity as αT when used at equimolar concentrations. In addition, we determined that the exposure time of RPE cells to α-tocopherol is critical for its ability to protect against oxidative damage. Lastly, we determined that αT, but not γT, partially requires the synthesis of new proteins within a 24-h period and prior to exposure to tBHP for optimal cytoprotection. We conclude that, unlike γT and δT, αT appears to be unique in its requirement for transport and/or signaling for it to be an effective antioxidant. As a result, more focus should be paid to which vitamin E components are used for antioxidant interventions.

scholarly journals The Zinc-Metallothionein Redox System Reduces Oxidative Stress in Retinal Pigment Epithelial Cells

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1874 ◽  
Author(s):  
Sara Rodríguez-Menéndez ◽  
Montserrat García ◽  
Beatriz Fernández ◽  
Lydia Álvarez ◽  
Andrés Fernández-Vega-Cueto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Redox System ◽  
Retinal Pigment Epithelial Cells ◽  
Oxygen Intermediates ◽  
Protective Mechanisms ◽  
Vitro Model

Oxidative stress affects all the structures of the human eye, particularly the retina and its retinal pigment epithelium (RPE). The RPE limits oxidative damage by several protective mechanisms, including the non-enzymatic antioxidant system zinc-metallothionein (Zn-MT). This work aimed to investigate the role of Zn-MT in the protection of RPE from the oxidative damage of reactive oxygen intermediates by analytical and biochemical-based techniques. The Zn-MT system was induced in an in vitro model of RPE cells and determined by elemental mass spectrometry with enriched isotopes and mathematical calculations. Induced-oxidative stress was quantified using fluorescent probes. We observed that 25, 50 or 100 μM of zinc induced Zn-MT synthesis (1.6-, 3.6- and 11.9-fold, respectively), while pre-treated cells with zinc (25, 50, and 100 μM) and subsequent 2,2′-Azobis(2-methylpropionamidine) dihydrochloride (AAPH) treatment increased Zn-MT levels in a lesser extent (0.8-, 2.1-, 6.1-fold, respectively), exerting a stoichiometric transition in the Zn-MT complex. Moreover, AAPH treatment decreased MT levels (0.4-fold), while the stoichiometry remained constant or slightly higher when compared to non-treated cells. Convincingly, induction of Zn-MT significantly attenuated oxidative stress produced by free radicals’ generators. We conclude that the stoichiometry of Zn-MT plays an important role in oxidative stress response, related with cellular metal homeostasis.

scholarly journals Curcumin regulates intracellular calcium release and inhibits oxidative stress parameters, VEGF, and caspase-3/-9 levels in human retinal pigment epithelium cells

2017 ◽  
Vol 104 (4) ◽  
pp. 301-315 ◽  
Author(s):  
H Bardak ◽  
AC Uğuz ◽  
Y Bardak
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment Epithelium ◽  
Intracellular Calcium ◽  
Blue Light ◽  
Caspase 3 ◽  
Calcium Release ◽  
Light Exposure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Expression Levels

In this study, we aimed to observe whether curcumin (cur), a polyphenolic compound derived from the dietary spice turmeric, a yellow substance obtained from the root of the plant Curcuma longa Linn, has any protective effect against blue light irradiation in human retinal pigment epithelium (ARPE-19) cells. For this purpose, we evaluated the intracellular calcium release mechanism, poly ADP ribose polymerase (PARP), procaspase-3/-9 protein expression levels, caspase activation, and reactive oxygen species levels. ARPE-19 cells were divided into four main groups, such as control, cur, blue light, and cur + blue light. Results were evaluated by Kruskal–Wallis and Mann–Whitney U tests as post hoc tests. The cells in cur and cur + blue light samples were incubated with 20 μM cur. Blue light exposure was performed for 24 h in an incubator. Lipid peroxidation and cytosolic-free Ca2+ [Ca2+]i concentrations were higher in the blue light exposure samples than in the control samples; however, their levels were determined as significantly lower in the cur and cur + blue light exposure samples than in the blue light samples alone. PARP and procaspase-3 levels were significantly higher in blue light samples. Cur administration significantly decreased PARP and procaspase-3 expression levels. Reduced glutathione and glutathione peroxidase values were lower in the blue light exposure samples, although they were higher in the cur and cur + blue light exposure samples. Caspase-3 and -9 activities were lower in the cur samples than in the blue light samples. Moreover, vascular endothelial growth factor (VEGF) levels were significantly higher in the blue light exposure samples. In conclusion, cur strongly induced regulatory effects on oxidative stress, intracellular Ca2+ levels, VEGF levels, PARP expression levels, and caspase-3 and -9 values in an experimental oxidative stress model in ARPE-19 cells.

scholarly journals Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Janusz Blasiak ◽  
Goran Petrovski ◽  
Zoltán Veréb ◽  
Andrea Facskó ◽  
Kai Kaarniranta
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Developed Countries ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
The Rich

Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE), Bruch’s membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD.

scholarly journals A Novel HDL-Mimetic Peptide HM-10/10 Protects RPE and Photoreceptors in Murine Models of Retinal Degeneration

2019 ◽  
Vol 20 (19) ◽  
pp. 4807 ◽  
Author(s):  
Feng Su ◽  
Christine Spee ◽  
Eduardo Araujo ◽  
Eric Barron ◽  
Mo Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Retinal Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Disease ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Mimetic Peptide ◽  
Age Related

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD. Oxidative stress plays a key role in the development of AMD. We generated a chimeric high-density lipoprotein (HDL), mimetic peptide named HM-10/10, with anti-oxidant properties and investigated its potential for the treatment of retinal disease using cell culture and animal models of RPE and photoreceptor (PR) degeneration. Treatment with HM-10/10 peptide prevented human fetal RPE cell death caused by tert-Butyl hydroperoxide (tBH)-induced oxidative stress and sodium iodate (NaIO3), which causes RPE atrophy and is a model of geographic atrophy in mice. We also show that HM-10/10 peptide ameliorated photoreceptor cell death and significantly improved retinal function in a mouse model of N-methyl-N-nitrosourea (MNU)-induced PR degeneration. Our results demonstrate that HM-10/10 protects RPE and retina from oxidant injury and can serve as a potential therapeutic agent for the treatment of retinal degeneration.

scholarly journals Protective Effect of Melatonin against Oxidative Stress-Induced Apoptosis and Enhanced Autophagy in Human Retinal Pigment Epithelium Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Chih-Chao Chang ◽  
Tien-Yi Huang ◽  
Hsin-Yuan Chen ◽  
Tsui-Chin Huang ◽  
Li-Chun Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Critical Role ◽  
Age Related Macular Degeneration ◽  
Cell Degeneration ◽  
Rpe Cells ◽  
Age Related ◽  
Human Rpe Cells

Age-related macular degeneration (AMD) affects the retinal macula and results in loss of vision, and AMD is the primary cause of blindness and severe visual impairment among elderly people worldwide. AMD is characterized by the accumulation of drusen in the Bruch’s membrane and dysfunction of retinal pigment epithelial (RPE) cells and photoreceptors. The pathogenesis of AMD remains unclear, and no effective treatment exists. Accumulating evidence indicates that oxidative stress plays a critical role in RPE cell degeneration and AMD. Melatonin is an antioxidant that scavenges free radicals, and it has anti-inflammatory, antitumor, and antiangiogenic effects. This study investigated the antioxidative, antiapoptotic, and autophagic effects of melatonin on oxidative damage to RPE cells. We used hydrogen peroxide (H2O2) to stimulate reactive oxygen species production to cause cell apoptosis in ARPE-19 cell lines. Our findings revealed that treatment with melatonin significantly inhibited H2O2-induced RPE cell damage, decreased the apoptotic rate, increased the mitochondrial membrane potential, and increased the autophagy effect. Furthermore, melatonin reduced the Bax/Bcl-2 ratio and the expression levels of the apoptosis-associated proteins cytochrome c and caspase 7. Additionally, melatonin upregulated the expression of the autophagy-related proteins LC3-II and Beclin-1 and downregulated the expression of p62. Thus, melatonin’s effects on autophagy and apoptosis can protect against H2O2-induced oxidative damage in human RPE cells. Melatonin may have multiple protective effects on human RPE cells against H2O2-induced oxidative damage.

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