ABCG1 Attenuates Oxidative Stress Induced by H2O2 through the Inhibition of NADPH Oxidase and the Upregulation of Nrf2-Mediated Antioxidant Defense in Endothelial Cells
Summary. Oxidative stress is an important factor that is related to endothelial dysfunction. ATP-binding cassette transporter G1 (ABCG1), a regulator of intracellular cholesterol efflux, has been found to prevent endothelial activation in vessel walls. To explore the role of ABCG1 in oxidative stres...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2020/2095645 |
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| author | Jiahong Xue Jiali Fan Yuan Li Wenhuan Wu Qing Yan Qiangsun Zheng |
| author_facet | Jiahong Xue Jiali Fan Yuan Li Wenhuan Wu Qing Yan Qiangsun Zheng |
| author_sort | Jiahong Xue |
| collection | DOAJ |
| description | Summary. Oxidative stress is an important factor that is related to endothelial dysfunction. ATP-binding cassette transporter G1 (ABCG1), a regulator of intracellular cholesterol efflux, has been found to prevent endothelial activation in vessel walls. To explore the role of ABCG1 in oxidative stress production in endothelial cells, HUAECs were exposed to H2O2 and transfected with the specific ABCG1 siRNA or ABCG1 overexpression plasmid. The results showed that overexpression of ABCG1 by ABCG1 plasmid or liver X receptor (LXR) agonist T0901317 treatment inhibited ROS production and MDA content induced by H2O2 in HUAECs. Furthermore, ABCG1 upregulation blunted the activity of prooxidant NADPH oxidase and the expression of Nox4, one of the NADPH oxidase subunits. Moreover, the increased migration of Nrf2 from the cytoplasm to the nucleus and antioxidant HO-1 expression were detected in HUAECs with upregulation of ABCG1. Conversely, ABCG1 downregulation by ABCG1 siRNA increased NADPH oxidase activity and Nox4 expression and abrogated the increase at Nrf2 nuclear protein levels. In addition, intracellular cholesterol load interfered with the balance between NADPH oxidase activity and HO-1 expression. It was suggested that ABCG1 attenuated oxidative stress induced by H2O2 in endothelial cells, which might be involved in the balance between decreased NADPH oxidase activity and increased Nrf2/OH-1 antioxidant defense signaling via its regulation for intracellular cholesterol accumulation. |
| format | Article |
| id | doaj-art-ce3998be6bd6406f9dbf5d7275bcfd8e |
| institution | DOAJ |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-ce3998be6bd6406f9dbf5d7275bcfd8e2025-08-20T03:19:39ZengWileyAnalytical Cellular Pathology2210-71772210-71852020-01-01202010.1155/2020/20956452095645ABCG1 Attenuates Oxidative Stress Induced by H2O2 through the Inhibition of NADPH Oxidase and the Upregulation of Nrf2-Mediated Antioxidant Defense in Endothelial CellsJiahong Xue0Jiali Fan1Yuan Li2Wenhuan Wu3Qing Yan4Qiangsun Zheng5Department of Cardiovascular Medicine, Second Affiliated Hospital of Xi’an Jiaotong University, 157 West Five Road, Xi’an, Shaanxi 710004, ChinaDepartment of Cardiovascular Medicine, Second Affiliated Hospital of Xi’an Jiaotong University, 157 West Five Road, Xi’an, Shaanxi 710004, ChinaDepartment of Cardiovascular Medicine, Second Affiliated Hospital of Xi’an Jiaotong University, 157 West Five Road, Xi’an, Shaanxi 710004, ChinaDepartment of Cardiovascular Medicine, Second Affiliated Hospital of Xi’an Jiaotong University, 157 West Five Road, Xi’an, Shaanxi 710004, ChinaDepartment of Cardiovascular Medicine, Second Affiliated Hospital of Xi’an Jiaotong University, 157 West Five Road, Xi’an, Shaanxi 710004, ChinaDepartment of Cardiovascular Medicine, Second Affiliated Hospital of Xi’an Jiaotong University, 157 West Five Road, Xi’an, Shaanxi 710004, ChinaSummary. Oxidative stress is an important factor that is related to endothelial dysfunction. ATP-binding cassette transporter G1 (ABCG1), a regulator of intracellular cholesterol efflux, has been found to prevent endothelial activation in vessel walls. To explore the role of ABCG1 in oxidative stress production in endothelial cells, HUAECs were exposed to H2O2 and transfected with the specific ABCG1 siRNA or ABCG1 overexpression plasmid. The results showed that overexpression of ABCG1 by ABCG1 plasmid or liver X receptor (LXR) agonist T0901317 treatment inhibited ROS production and MDA content induced by H2O2 in HUAECs. Furthermore, ABCG1 upregulation blunted the activity of prooxidant NADPH oxidase and the expression of Nox4, one of the NADPH oxidase subunits. Moreover, the increased migration of Nrf2 from the cytoplasm to the nucleus and antioxidant HO-1 expression were detected in HUAECs with upregulation of ABCG1. Conversely, ABCG1 downregulation by ABCG1 siRNA increased NADPH oxidase activity and Nox4 expression and abrogated the increase at Nrf2 nuclear protein levels. In addition, intracellular cholesterol load interfered with the balance between NADPH oxidase activity and HO-1 expression. It was suggested that ABCG1 attenuated oxidative stress induced by H2O2 in endothelial cells, which might be involved in the balance between decreased NADPH oxidase activity and increased Nrf2/OH-1 antioxidant defense signaling via its regulation for intracellular cholesterol accumulation.http://dx.doi.org/10.1155/2020/2095645 |
| spellingShingle | Jiahong Xue Jiali Fan Yuan Li Wenhuan Wu Qing Yan Qiangsun Zheng ABCG1 Attenuates Oxidative Stress Induced by H2O2 through the Inhibition of NADPH Oxidase and the Upregulation of Nrf2-Mediated Antioxidant Defense in Endothelial Cells Analytical Cellular Pathology |
| title | ABCG1 Attenuates Oxidative Stress Induced by H2O2 through the Inhibition of NADPH Oxidase and the Upregulation of Nrf2-Mediated Antioxidant Defense in Endothelial Cells |
| title_full | ABCG1 Attenuates Oxidative Stress Induced by H2O2 through the Inhibition of NADPH Oxidase and the Upregulation of Nrf2-Mediated Antioxidant Defense in Endothelial Cells |
| title_fullStr | ABCG1 Attenuates Oxidative Stress Induced by H2O2 through the Inhibition of NADPH Oxidase and the Upregulation of Nrf2-Mediated Antioxidant Defense in Endothelial Cells |
| title_full_unstemmed | ABCG1 Attenuates Oxidative Stress Induced by H2O2 through the Inhibition of NADPH Oxidase and the Upregulation of Nrf2-Mediated Antioxidant Defense in Endothelial Cells |
| title_short | ABCG1 Attenuates Oxidative Stress Induced by H2O2 through the Inhibition of NADPH Oxidase and the Upregulation of Nrf2-Mediated Antioxidant Defense in Endothelial Cells |
| title_sort | abcg1 attenuates oxidative stress induced by h2o2 through the inhibition of nadph oxidase and the upregulation of nrf2 mediated antioxidant defense in endothelial cells |
| url | http://dx.doi.org/10.1155/2020/2095645 |
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