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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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/5151168 |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-8c37beae5ce74cb686f0c90bff3a6a10 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-8c37beae5ce74cb686f0c90bff3a6a102025-02-03T06:46:24ZengWileyJournal of Immunology Research2314-71562021-01-01202110.1155/2021/5151168Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE PathwayYajuan Lin0Yunpeng Xie1Zhujing Hao2Hailian Bi3Yang Liu4Xiaolei Yang5Yunlong Xia6Department of CardiologyDepartment of CardiologyDepartment of CardiologyDepartment of CardiologyDepartment of CardiologyDepartment of CardiologyDepartment of CardiologyUric 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.http://dx.doi.org/10.1155/2021/5151168 |
| spellingShingle | 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 Journal of Immunology Research |
| title | 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_short | 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 |
| url | http://dx.doi.org/10.1155/2021/5151168 |
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