Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway

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 en...

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Autores principales:	Yajuan Lin, Yunpeng Xie, Zhujing Hao, Hailian Bi, Yang Liu, Xiaolei Yang, Yunlong Xia
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/8c37beae5ce74cb686f0c90bff3a6a10
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spelling	oai:doaj.org-article:8c37beae5ce74cb686f0c90bff3a6a102021-11-15T01:20:07ZProtective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway2314-715610.1155/2021/5151168https://doaj.org/article/8c37beae5ce74cb686f0c90bff3a6a102021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/5151168https://doaj.org/toc/2314-7156Uric 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.Yajuan LinYunpeng XieZhujing HaoHailian BiYang LiuXiaolei YangYunlong XiaHindawi LimitedarticleImmunologic diseases. AllergyRC581-607ENJournal of Immunology Research, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607
spellingShingle	Immunologic diseases. Allergy RC581-607 Yajuan Lin Yunpeng Xie Zhujing Hao Hailian Bi Yang Liu Xiaolei Yang Yunlong Xia Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway
description	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.
format	article
author	Yajuan Lin Yunpeng Xie Zhujing Hao Hailian Bi Yang Liu Xiaolei Yang Yunlong Xia
author_facet	Yajuan Lin Yunpeng Xie Zhujing Hao Hailian Bi Yang Liu Xiaolei Yang Yunlong Xia
author_sort	Yajuan Lin
title	Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway
title_short	Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway
title_full	Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway
title_fullStr	Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway
title_full_unstemmed	Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway
title_sort	protective effect of uric acid on ox-ldl-induced huvecs injury via keap1-nrf2-are pathway
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/8c37beae5ce74cb686f0c90bff3a6a10
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Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway

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