期刊
CNS NEUROSCIENCE & THERAPEUTICS
卷 19, 期 9, 页码 675-681出版社
WILEY-BLACKWELL
DOI: 10.1111/cns.12131
关键词
Apoptosis; Hyperglycemia; NADPH oxidase; Resveratrol; Vascular endothelial cells
资金
- National Basic Research Program of China (973 Program) [2011CB504002]
- Knowledge Innovation Program of the Chinese Academy of Sciences [KSCX2-EW-R-10]
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 bEnd3, 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 Nox1 but not Nox2, Nox4, and p22(phox) expression through NF-B 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-B activation, NADPH oxidase activity elevation, and ROS production. Conclusions HG induces endothelial cell apoptosis through NF-B/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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