Idebenone Prevents Oxidative Stress, Cell Death and Senescence of Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio

Arend, Nicole; Wertheimer, Christian; Laubichler, Peter; Wolf, Armin; Kernt, Marcus

doi:10.1159/000381726

Cited by 39 publications

(26 citation statements)

References 49 publications

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“…Arend et al . treated ARPE 19 cells with hydrogen peroxide for 2 hours (400 to 2000 MCM) and found no change in cell viability at 400 MCM [8]. This is contrary to our results in the present study showing a significant decrease in cell viability at 300, 400 and 800 MCM Fig.…”

Section: Discussioncontrasting

confidence: 99%

“…In another study, Yu et al . treated primary cultures of human retinal pigment epithelial cells (at low passages P3-P5) with low hydrogen peroxide concentrations (50-150 MCM) [8]. In comparison to our study using a different cell line (ARPE19 with senescent-related changes), a direct comparison of results between our studies is not readily relevant.…”

Section: Discussionmentioning

confidence: 85%

“…Furthermore, hydrogen peroxide treatment also inhibited cell proliferation. Considering that our study focuses only on acute exposure to hydrogen peroxide, it clearly indicates that oxidative stress could possibly play a role in the pathogenesis of AMD [7, 8]. Additional studies such as inhibition of oxidative damage and supplementation with antioxidants will further validate this premise and shed more light on the nature of AMD development [10, 11].…”

Section: Resultsmentioning

confidence: 99%

“…Others have reported oxidative stress on human retinal pigment epithelial cells in culture [8, 9]. Arend et al .…”

Section: Discussionmentioning

confidence: 99%

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Oxidative Stress Induces Senescence in Cultured RPE Cells

Aryan¹,

Betts-Obregon²,

Perry³

et al. 2016

TONEUJ

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The aim of this research is to determine whether oxidative stress induces cellular senescence in human retinal pigment epithelial cells. Cultured ARPE19 cells were subjected to different concentrations of hydrogen peroxide to induce oxidative stress. Cells were seeded into 24-well plates with hydrogen peroxide added to cell medium and incubated at 37°C + 5% CO2 for a 90-minute period at 0, 300, 400 and 800 micromolar (MCM) hydrogen peroxide. The number of viable ARPE19 cells were recorded using the Trypan Blue Dye Exclusion Method and cell senescence was measured by positive staining for senescence-associated beta-galactosidase (SA-beta-Gal) protein. Without hydrogen peroxide treatment, the number of viable ARPE19 cells increased significantly from 50,000 cells/well to 197,000 within 72 hours. Treatment with hydrogen peroxide reduced this level of cell proliferation significantly (to 52,167 cells at 400 MCM; to 49,263 cells at 800 MCM). Meanwhile, a high level of positive senescence-indicator SA-Beta-Gal staining was induced by hydrogen peroxide treatment (from a baseline level of 12% to 80% at 400 and 800 MCM). Our data suggest that oxidative stress from hydrogen peroxide treatment inhibited ARPE19 cell proliferation and induced cellular senescence.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

“…Others have reported oxidative stress on human retinal pigment epithelial cells in culture [8, 9]. Arend et al .…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Oxidative Stress Induces Senescence in Cultured RPE Cells

Aryan¹,

Betts-Obregon²,

Perry³

et al. 2016

TONEUJ

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“…Finally, we investigated the effect of RSV on f‐LSCs. It is known that RVS and other polyphenols have beneficial effects on several anterior eye cells‐based diseases and promote differentiation in vitro culture . Our findings show that RSV treatment does not affect f‐LSCs viability, whereas it outlines a limbal epithelial progenitor‐like molecular profile characterised by expression of sox17, pax6, ΔNp63α, CK15 and emphasises involvement of profilin‐1, integrin‐β1 and nanog.…”

Section: Discussionmentioning

confidence: 56%

PFN1 and integrin‐β1/mTOR axis involvement in cornea differentiation of fibroblast limbal stem cells

Tomasello

Coppola

Pitrone

et al. 2019

J Cellular Molecular Medi

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Ex vivo limbal stem cell transplantation is the main therapeutic approach to address a complete and functional re‐epithelialization in corneal blindness, the second most common eye disorder. Although important key points were defined, the molecular mechanisms involved in the epithelial phenotype determination are unclear. Our previous studies have demonstrated the pluripotency and immune‐modulatory of fibroblast limbal stem cells (f‐LSCs), isolated from the corneal limbus. We defined a proteomic profile especially enriched in wound healing and cytoskeleton‐remodelling proteins, including Profilin‐1 (PFN1). In this study we postulate that pfn‐1 knock down promotes epithelial lineage by inhibiting the integrin‐β1(CD29)/mTOR pathway and subsequent NANOG down‐expression. We showed that it is possible modulate pfn1 expression levels by treating f‐LSCs with Resveratrol (RSV), a natural compound: pfn1 decline is accompanied with up‐regulation of the specific differentiation epithelial genes pax6 (paired‐box 6), sox17 (sex determining region Y‐box 17) and ΔNp63‐α (p63 splice variant), consistent with drop‐down of the principle stem gene levels. These results contribute to understand the molecular biology of corneal epithelium development and suggest that pfn1 is a potential molecular target for the treatment of corneal blindness based on epithelial cell dysfunction.

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Improved Mitochondrial Metabolism and Reduced Inflammation Following Attenuation of Murine Lupus With Coenzyme Q10 Analog Idebenone

Blanco

Pedersen

Wang

et al. 2020

Arthritis & Rheumatology

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Objective A role for mitochondrial dysfunction has been proposed in the immune dysregulation and organ damage characteristic of systemic lupus erythematosus (SLE). Idebenone is a coenzyme Q10 synthetic quinone analog and an antioxidant that has been used in humans to treat diverse diseases in which mitochondrial function is impaired. This study was undertaken to assess whether idebenone ameliorates lupus in murine models. Methods Idebenone was administered orally to MRL/lpr mice at 2 different doses (1 gm/kg or 1.5 gm/kg idebenone‐containing diet) for 8 weeks. At peak disease activity, clinical, immunologic, and metabolic parameters were analyzed and compared to those in untreated mice (n = 10 per treatment group). Results were confirmed in the lupus‐prone NZM2328 mouse model. Results In MRL/lpr mice, idebenone‐treated mice showed a significant reduction in mortality incidence (P < 0.01 versus untreated mice), and the treatment attenuated several disease features, including glomerular inflammation and fibrosis (each P < 0.05 versus untreated mice), and improved renal function in association with decreased renal expression of interleukin‐17A (IL‐17A) and mature IL‐18. Levels of splenic proinflammatory cytokines and inflammasome‐related genes were significantly decreased (at least P < 0.05 and some with higher significance) in mice treated with idebenone, while no obvious drug toxicity was observed. Idebenone inhibited neutrophil extracellular trap formation in neutrophils from lupus‐prone mice (P < 0.05) and human patients with SLE. Idebenone also improved mitochondrial metabolism (30% increase in basal respiration and ATP production), reduced the extent of heart lipid peroxidation (by one‐half that of untreated mice), and significantly improved endothelium‐dependent vasorelaxation (P < 0.001). NZM2328 mice exposed to idebenone also displayed improvements in renal and systemic inflammation, reducing the kidney pathology score (P < 0.05), IgG/C3 deposition (P < 0.05), and the gene expression of interferon, proinflammatory, and inflammasome‐related genes (at least P < 0.05 and some with higher significance). Conclusion Idebenone ameliorates murine lupus disease activity and the severity of organ damage, supporting the hypothesis that agents that modulate mitochondrial biologic processes may have a therapeutic role in human SLE.

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Idebenone Prevents Oxidative Stress, Cell Death and Senescence of Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio

Cited by 39 publications

References 49 publications

Oxidative Stress Induces Senescence in Cultured RPE Cells

Oxidative Stress Induces Senescence in Cultured RPE Cells

PFN1 and integrin‐β1/mTOR axis involvement in cornea differentiation of fibroblast limbal stem cells

Improved Mitochondrial Metabolism and Reduced Inflammation Following Attenuation of Murine Lupus With Coenzyme Q10 Analog Idebenone

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