Resveratrol Protects Against Hydroquinone-Induced Oxidative Threat in Retinal Pigment Epithelial Cells.

Abstract

Purpose

Oxidative stress in retinal pigment epithelial (RPE) cells is associated with age-related macular degeneration (AMD). Resveratrol exerts a range of protective biologic effects, but its mechanism(s) are not well understood. The aim of this study was to investigate how resveratrol could affect biologic pathways in oxidatively stressed RPE cells.

Methods

Cultured human RPE cells were treated with hydroquinone (HQ) in the presence or absence of resveratrol. Cell viability was determined with WST-1 reagent and trypan blue exclusion. Mitochondrial function was measured with the XFe24 Extracellular Flux Analyzer. Expression of heme oxygenase-1 (HO-1) and glutamate cysteine ligase catalytic subunit was evaluated by qPCR. Endoplasmic reticulum stress protein expression was measured by Western blot. Potential reactions between HQ and resveratrol were investigated using high-performance liquid chromatography mass spectrometry with resveratrol and additional oxidants for comparison.

Results

RPE cells treated with the combination of resveratrol and HQ had significantly increased cell viability and improved mitochondrial function when compared with HQ-treated cells alone. Resveratrol in combination with HQ significantly upregulated HO-1 mRNA expression above that of HQ-treated cells alone. Resveratrol in combination with HQ upregulated C/EBP homologous protein and spliced X-box binding protein 1. Additionally, new compounds were formed from resveratrol and HQ coincubation.

Conclusions

Resveratrol can ameliorate HQ-induced toxicity in RPE cells through improved mitochondrial bioenergetics, upregulated antioxidant genes, stimulated unfolded protein response, and direct oxidant interaction. This study provides insight into pathways through which resveratrol can protect RPE cells from oxidative damage, a factor thought to contribute to AMD pathogenesis.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1167/iovs.61.4.32

Publication Info

Neal, Samantha E, Kristen L Buehne, Nicholas A Besley, Ping Yang, Peter Silinski, Jiyong Hong, Ian T Ryde, Joel N Meyer, et al. (2020). Resveratrol Protects Against Hydroquinone-Induced Oxidative Threat in Retinal Pigment Epithelial Cells. Investigative ophthalmology & visual science, 61(4). p. 32. 10.1167/iovs.61.4.32 Retrieved from https://hdl.handle.net/10161/30149.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Silinski

Peter Silinski

Research Associate, Senior

Director, Chemistry Shared Instrumentation Facility

The Duke Chemistry Shared Instrumentation Facility houses modern and diverse instrumentation for a range of analytical needs, including mass spectrometry, nuclear magnetic resonance, and a variety of supporting instruments. Most shared instruments are available for walk-up use by Duke researchers once they have received the required training.

Hong

Jiyong Hong

Professor of Chemistry

Research in the Hong group focuses on using chemical tools, in particular small molecules, to understand the signaling pathways in biology. We synthesize biologically interesting natural products and screen small molecule libraries to identify modulators of biological processes. Then, we explore their modes of action in order to investigate intracellular signaling pathways and identify novel targets for drug design. In addition, we design and develop unique and efficient synthetic strategies that will allow rapid access to molecular complexity and structural diversity. Through multidisciplinary approaches, including organic synthesis, molecular biology, and cell biology, the cellular components and molecular events that embody cancer, immune response, and GPCR signaling have systematically been explored. Compounds employed in these studies could also advance the development of novel therapeutics for the treatment of human diseases.

  1. Synthesis of Natural Products and Study of Mode of Action: We synthesize biologically interesting natural products and explore the modes of action in order to investigate intracellular signaling pathways and identify novel targets for drug design. Completed target molecules include largazole (a marine natural product with HDAC inhibitory activity), brasilibactin A (a cytotoxic siderophore), manassantins A and B (natural products with anti-HIF-1 activity), and subglutinols A and B (natural products with immunosuppressive activity).
  2. Development of Novel Synthetic Methodology: We design and develop unique and efficient synthetic strategies which will allow rapid access to molecular complexity and structural diversity. A specific area of interest includes the development of novel methods for the stereoselective synthesis of substituted tetrahydrofurans and tetrahydropyrans.
  3. Screen of Small Molecule Libraries for Identification of Small Molecule Modulators of Biological Processes: With the advent of combinatorial chemistry and other synthetic technologies, it is feasible to prepare large collections of synthetic organic molecules. These libraries are useful in providing molecules that can be used to probe relevant biological pathways. We are interested in identification of modulators of biological processes, including drug abuse and neurodegenerative diseases.

Through multidisciplinary approaches, the cellular components and molecular events that embody cancer, immune response, and neurodegenerative diseases are systematically explored. Compounds employed in these studies could also advance the development of novel therapeutics for the treatment of human diseases.
Meyer

Joel Meyer

Professor of Environmental Genomics in the Division of Environmental Sciences and Policy

Dr. Meyer studies the effects of toxic agents and stressors on human and wildlife health. He is particularly interested in understanding the mechanisms by which environmental agents cause DNA damage, the molecular processes that organisms employ to protect prevent and repair DNA damage, and genetic differences that may lead to increased or decreased sensitivity to DNA damage. Mitochondrial DNA damage and repair, as well as mitochondrial function in general, are a particular focus. He studies these effects in the nematode Caenorhabditis elegans, in cell culture, and collaboratively in other laboratory model organisms as well as in human populations in the USA and globally.


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