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.

中文翻译：

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ABCG1 通过抑制 NADPH 氧化酶和上调 Nrf2 介导的内皮细胞抗氧化防御来减弱 H2O2 诱导的氧化应激

总结。氧化应激是与内皮功能障碍相关的重要因素。已发现 ATP 结合盒转运蛋白 G1 (ABCG1) 是细胞内胆固醇流出的调节剂，可防止血管壁中的内皮活化。为了探索 ABCG1 在内皮细胞氧化应激产生中的作用，将 HUAECs 暴露于 H ₂ O ₂并用特定的 ABCG1 siRNA 或 ABCG1 过表达质粒转染。结果表明，ABCG1质粒或肝X受体（LXR）激动剂T0901317处理过表达ABCG1可抑制H ₂ O ₂诱导的ROS产生和MDA含量在 HUAEC。此外，ABCG1 上调减弱了促氧化 NADPH 氧化酶的活性和 NADPH 氧化酶亚基之一 Nox4 的表达。此外，在 ABCG1 上调的 HUAEC 中检测到 Nrf2 从细胞质到细胞核的迁移增加和抗氧化剂 HO-1 的表达。相反，ABCG1 siRNA 对 ABCG1 的下调增加了 NADPH 氧化酶活性和 Nox4 表达，并消除了 Nrf2 核蛋白水平的增加。此外，细胞内胆固醇负荷干扰了 NADPH 氧化酶活性和 HO-1 表达之间的平衡。表明ABCG1减弱了H ₂ O ₂诱导的氧化应激 在内皮细胞中，这可能通过调节细胞内胆固醇积累参与降低 NADPH 氧化酶活性和增加 Nrf2/OH-1 抗氧化防御信号之间的平衡。