Resveratrol Protects Vascular Endothelial Cells from High Glucose–Induced Apoptosis through Inhibition of NADPH Oxidase Activation–Driven Oxidative Stress
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Summary: Introduction: Hyperglycemia‐induced oxidative stress has been implicated in diabetic vascular complications in which NADPH oxidase is a major source of reactive oxygen species ( ROS ) generation. Resveratrol is a naturally occurring polyphenol, which has vasoprotective effects in diabetic animal models and inhibits high glucose ( HG )–induced oxidative stress in endothelial cells. Aims: We aimed to examine whether HG ‐induced NADPH oxidase activation and ROS production contribute to glucotoxicity to endothelial cells and the effect of resveratrol on glucotoxicity. Results: Using a murine brain microvascular endothelial cell line bE nd3, we found that NADPH oxidase inhibitor (apocynin) and resveratrol both inhibited HG ‐induced endothelial cell apoptosis. HG ‐induced elevation of NADPH oxidase activity and production of ROS were inhibited by apocynin, suggesting that HG induces endothelial cell apoptosis through NADPH oxidase–mediated ROS production. Mechanistic studies revealed that HG upregulated NADPH oxidase subunit N ox1 but not N ox2, N ox4, and p22 phox expression through NF ‐κB activation, which resulted in elevation of NADPH oxidase activity and consequent ROS production. Resveratrol prevented HG ‐induced endothelial cell apoptosis through inhibiting HG ‐induced NF ‐κB activation, NADPH oxidase activity elevation, and ROS production. Conclusions: HG induces endothelial cell apoptosis through NF ‐κB/ NADPH oxidase/ ROS pathway, which was inhibited by resveratrol. Our findings provide new potential therapeutic targets against brain vascular complications of diabetes.
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Studies have shown links between high NOX1 levels and hypertension, diabetes, ischemia/reperfusion injury, and coronary artery disease.
“Increased NOX1 activity is associated with vascular disease, and studies have shown links between high NOX1 levels and hypertension (1015), diabetes (163, 380, 1003), ischemia/reperfusion injury (479), and coronary artery disease (393).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [163]
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- ª 2013 John Wiley & Sons Ltd CNS Neuroscience & Therapeutics 19 (2013) 675-681 681
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Retracted
- Authors
- Chen, F., Qian, L., Deng, B., Liu, Z., Zhao, Y., & Le, Y.
- Affiliations
- Second Military Medical University (CN)
- Key Laboratory of Food Safety Research Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China
- Chinese Academy of Sciences (CN)
- Department of Endocrinology Changzheng Hospital Second Military Medical University Shanghai China
- Corresponding author
- Zhao, Ying
- Venue
- CNS Neuroscience & Therapeutics
- Publisher
- Wiley
- Published
- 2013-06-03
- Volume
- 19
- Issue
- 9
- Pages
- 675-681
- ISSN
- 1755-5930 (ISSN-L)
- 1755-5949
- PMC
- PMC6493644
- OpenAlex
- W2054720870
- Cited by
- 101
- References
- 36
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 6 · 2021: 7 · 2020: 13 · 2019: 10 · 2018: 7 · 2017: 11 · 2016: 9 · 2015: 7 · 2014: 9 · 2013: 5
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- CNS Neuroscience & Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- McGill University
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- resveratrol, high glucose, endothelial cell apoptosis, NADPH oxidase, oxidative stress, reactive oxygen species, NF-κB activation, NOX1, apocynin, glucotoxicity, diabetic vascular complications, brain microvascular endothelial cells, polyphenols
- MeSH terms
- NADPH Oxidase 1, Resveratrol, Animals, Cells, Cultured, Enzyme Activation, Glucose, NADH, NADPH Oxidoreductases, Stilbenes, NF-kappa B, Apoptosis, Reactive Oxygen Species, Oxidative Stress, NADPH Oxidases, Endothelial Cells, Mice
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