Uptake and Protective Effects of Ergothioneine in Human Endothelial Cells
Publication in refereed journal

香港中文大學研究人員

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摘要Ergothioneine is a thiourea derivative of histidine found in food, especially mushrooms. Experiments in cell-free systems and chemical assays identified this compound as a powerful antioxidant. Experiments were designed to test the ability of endothelial cells to take up ergothioneine and hence benefit from protection against oxidative stress. Reverse-transcription polymerase chain reaction and Western blotting demonstrated transcription and translation of an ergothioneine transporter in human brain microvascular endothelial cells (HBMECs). Uptake of [H-3] ergothioneine occurred by the organic cation transporter novel type-1 (OCTN-1), was sodium-dependent, and was reduced when expression of OCTN-1 was silenced by small interfering RNA (siRNA). The effect of ergothioneine on the production of reactive oxygen species (ROS) in HBMECs was measured using dichlorodihydrofluorescein and lucigenin, and the effect on cell viability was studied using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay. ROS production and cell death induced by pyrogallol, xanthine oxidase plus xanthine, and high glucose were suppressed by ergothioneine. The antioxidant and cytoprotective effects of ergothioneine were abolished when OCTN-1 was silenced using siRNA. The expression of NADPH oxidase 1 was decreased, and those of glutathione reductase, catalase, and superoxide dismutase enhanced by the compound. In isolated rat basilar arteries, ergothioneine attenuated the reduction in acetylcholine-induced relaxation caused by pyrogallol, xanthine oxidase plus xanthine, or incubation in high glucose. Chronic treatment with the compound improved the response to acetylcholine in arteries of rats with streptozotocin-induced diabetes. In summary, ergothioneine is taken up by endothelial cells via OCTN-1, where the compound then protects against oxidative stress, curtailing endothelial dysfunction.
著者Li RWS, Yang C, Sit ASM, Kwan YW, Lee SMY, Hoi MPM, Chan SW, Hausman M, Vanhoutte PM, Leung GPH
期刊名稱Journal of Pharmacology and Experimental Therapeutics
出版年份2014
月份9
日期1
卷號350
期次3
出版社AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
頁次691 - 700
國際標準期刊號0022-3565
電子國際標準期刊號1521-0103
語言英式英語
Web of Science 學科類別Pharmacology & Pharmacy

上次更新時間 2020-24-11 於 23:05