PMID- 33344146 OWN - NLM STAT- MEDLINE DCOM- 20210826 LR - 20210826 IS - 2210-7185 (Electronic) IS - 2210-7177 (Print) IS - 2210-7177 (Linking) VI - 2020 DP - 2020 TI - ABCG1 Attenuates Oxidative Stress Induced by H(2)O(2) through the Inhibition of NADPH Oxidase and the Upregulation of Nrf2-Mediated Antioxidant Defense in Endothelial Cells. PG - 2095645 LID - 10.1155/2020/2095645 [doi] LID - 2095645 AB - 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 H(2)O(2) 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 H(2)O(2) 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 H(2)O(2) 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. CI - Copyright (c) 2020 Jiahong Xue et al. FAU - Xue, Jiahong AU - Xue J AUID- ORCID: 0000-0003-1079-4767 AD - Department of Cardiovascular Medicine, Second Affiliated Hospital of Xi'an Jiaotong University, 157 West Five Road, Xi'an, Shaanxi 710004, China. FAU - Fan, Jiali AU - Fan J AD - Department of Cardiovascular Medicine, Second Affiliated Hospital of Xi'an Jiaotong University, 157 West Five Road, Xi'an, Shaanxi 710004, China. FAU - Li, Yuan AU - Li Y AD - Department of Cardiovascular Medicine, Second Affiliated Hospital of Xi'an Jiaotong University, 157 West Five Road, Xi'an, Shaanxi 710004, China. FAU - Wu, Wenhuan AU - Wu W AD - Department of Cardiovascular Medicine, Second Affiliated Hospital of Xi'an Jiaotong University, 157 West Five Road, Xi'an, Shaanxi 710004, China. FAU - Yan, Qing AU - Yan Q AD - Department of Cardiovascular Medicine, Second Affiliated Hospital of Xi'an Jiaotong University, 157 West Five Road, Xi'an, Shaanxi 710004, China. FAU - Zheng, Qiangsun AU - Zheng Q AUID- ORCID: 0000-0003-2344-4627 AD - Department of Cardiovascular Medicine, Second Affiliated Hospital of Xi'an Jiaotong University, 157 West Five Road, Xi'an, Shaanxi 710004, China. LA - eng PT - Journal Article DEP - 20201203 PL - United States TA - Anal Cell Pathol (Amst) JT - Analytical cellular pathology (Amsterdam) JID - 101541993 RN - 0 (ABCG1 protein, human) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (Antioxidants) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Protein Subunits) RN - 97C5T2UQ7J (Cholesterol) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.6.3.- (NADPH Oxidases) SB - IM MH - ATP Binding Cassette Transporter, Subfamily G, Member 1/*metabolism MH - Antioxidants/*metabolism MH - Cholesterol/metabolism MH - Endothelial Cells/drug effects/*metabolism MH - Heme Oxygenase-1/metabolism MH - Humans MH - Hydrogen Peroxide/*toxicity MH - NADPH Oxidases/*metabolism MH - NF-E2-Related Factor 2/*metabolism MH - Oxidation-Reduction/drug effects MH - *Oxidative Stress/drug effects MH - Protein Subunits/metabolism MH - Umbilical Arteries/pathology MH - *Up-Regulation/drug effects PMC - PMC7732382 COIS- There are no conflicts to declare for this submission. EDAT- 2020/12/22 06:00 MHDA- 2021/08/27 06:00 PMCR- 2020/12/03 CRDT- 2020/12/21 06:07 PHST- 2020/07/13 00:00 [received] PHST- 2020/10/23 00:00 [accepted] PHST- 2020/12/21 06:07 [entrez] PHST- 2020/12/22 06:00 [pubmed] PHST- 2021/08/27 06:00 [medline] PHST- 2020/12/03 00:00 [pmc-release] AID - 10.1155/2020/2095645 [doi] PST - epublish SO - Anal Cell Pathol (Amst). 2020 Dec 3;2020:2095645. doi: 10.1155/2020/2095645. eCollection 2020.