Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway.
Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway.
复制标题
尿酸通过 Keap1-Nrf2-ARE 通路对 ox-LDL 诱导的 HUVEC 损伤的保护作用
DOI：
10.1155/2021/5151168
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发表时间：
2021
影响因子：
4.1
通讯作者：
Xia Y
中科院分区：
文献类型：
--
作者：
Lin Y;Xie Y;Hao Z;Bi H;Liu Y;Yang X;Xia Y
尿酸是一种有效的抗氧化剂。氧化低密度脂蛋白(OX-LDL)来源于循环中的低密度脂蛋白，促进动脉粥样硬化。Keap1-Nrf2-ARE途径是机体抵御内外氧化损伤的关键途径。尿酸在氧化低密度脂蛋白损伤血管内皮细胞功能中的作用及其对Keap1-Nrf2-ARE通路的影响尚未得到充分的研究。体外用不同浓度的尿酸和氧化低密度脂蛋白处理人脐静脉内皮细胞，观察尿酸对血管内皮细胞的影响。用流式细胞仪和Western印迹法检测细胞表型。免疫荧光法测定Nrf2的核转位。免疫共沉淀法测定Nrf2泛素化水平。用微流控装置模拟体内血管环境，用RT-PCR法检测炎症因子的mRNA水平。本研究的结果表明，适当的尿酸可以显著减轻ox-LDL引起的内皮损伤，如氧化应激、炎症和粘附性增加。此外，尿酸减少了Nrf2的泛素化，增加了Nrf2蛋白的核转位，从而激活了Keap1-Nrf2-ARE途径，起到了保护作用。有趣的是，UA的作用被给予Nrf2的抑制剂布鲁塞尔醇显著抑制。综上所述，适当浓度的尿酸可以通过Nrf2核转位减轻内皮细胞的氧化应激水平，进一步保护细胞免受损伤。
Uric acid is an effective antioxidant. Oxidized low-density lipoprotein (ox-LDL) is derived from circulating LDL and promotes atherosclerosis. The Keap1-Nrf2-ARE pathway is a key body pathway involved in protection against internal and external oxidative damages. The role of uric acid on vascular endothelial function damaged by ox-LDL, and its effect on the Keap1-Nrf2-ARE pathway has not been fully explored. HUVECs were treated with different concentrations of uric acid and ox-LDL to explore the effect of uric acid in vitro. Cell phenotype was determined by cytometry and Western blot. Nuclear translocation of Nrf2 was determined by immunofluorescence. Coimmunoprecipitation was used to determine the level of Nrf2 ubiquitination. A microfluidic device was used to mimic the vascular environment in the body, and the level of mRNA levels of inflammatory factors was determined by RT-PCR. The findings of this study show that suitable uric acid can significantly reduce endothelial damage caused by ox-LDL, such as oxidative stress, inflammation, and increased adhesion. In addition, uric acid reduced Nrf2 ubiquitination and increased nuclear translocation of Nrf2 protein, thus activating the Keap1-Nrf2-ARE pathway and playing a protective role. Interestingly, the effects of UA were significantly inhibited by administration of Brusatol, an inhibitor of Nrf2. In summary, suitable concentrations of uric acid can alleviate the oxidative stress level of endothelial cells through Nrf2 nuclear translocation and further protect cells from damage.
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影响因子：
--
作者：
Mao, Huimin;Tao, Tianqi;Shi, Dazhuo
通讯作者：
Shi, Dazhuo
影响因子：
3.5
作者：
Kuwabara, Masanari;Niwa, Koichiro;Hisatome, Ichiro
通讯作者：
Hisatome, Ichiro
DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P
影响因子：
3.5
作者：
Cheng Di;Du Rui;Lu Jie Li
通讯作者：
Lu Jie Li
影响因子：
2.8
作者：
Mannarino, Elmo;Pirro, Matteo
通讯作者：
Pirro, Matteo