5,2'-Dibromo-2,4',5'-trihydroxydiphenylmethanone Inhibits LPS-Induced Vascular Inflammation by Targeting the Cav1 Protein.
5,2'-Dibromo-2,4',5'-trihydroxydiphenylmethanone Inhibits LPS-Induced Vascular Inflammation by Targeting the Cav1 Protein.
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DOI：
10.3390/molecules27092884
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发表时间：
2022-04-30
期刊：
影响因子：
4.6
通讯作者：
Li, Qingshan
中科院分区：
文献类型：
--
作者：
Yuan, Hongxia;Hou, Qianyi;Feng, Xiue;Zhang, Yuanlin;Yang, Fan;Ge, Rui;Li, Qingshan
关键词：
血管炎症直接导致动脉粥样硬化。5，2 ′-二溴-2，4 ′，5 ′-三羟基二苯甲酮（TDD）是一种合成的溴苯酚衍生物，具有抗动脉粥样硬化和抗炎作用。然而，潜在的途径尚不清楚。在这项研究中，我们首先研究了TDD对Toll样受体-4（TLR 4）活性的影响，即脂多糖（LPS）的信号受体，发现TDD在体内不抑制LPS诱导的EA.hy926细胞和血管壁中TLR 4的表达。接下来，我们研究了全局蛋白质的变化和TDD在LPS处理的EA.hy926细胞中的作用机制，使用同量异位素标签进行相对和绝对定量技术。Western blot分析显示，TDD通过调节IκBα的磷酸化和随后的降解来抑制NF-κB的活化。在差异表达的蛋白质中，TDD浓度依赖性地抑制Caveolin 1（Cav 1）的表达。采用生物膜干涉法、紫外-可见吸收光谱、荧光光谱和分子对接等方法研究了Cav 1与TDD的相互作用。我们发现TDD可以通过氢键和货车范德华力直接与Cav 1结合。总之，我们的结果表明，TDD抑制LPS诱导的血管炎症和NF-κB信号通路特异性靶向Cav 1蛋白。TDD可能是一种新的抗炎化合物，特别是用于治疗动脉粥样硬化。
Vascular inflammation is directly responsible for atherosclerosis. 5,2′-Dibromo-2,4′,5′-trihydroxydiphenylmethanone (TDD), a synthetic bromophenol derivative, exhibits anti-atherosclerosis and anti-inflammatory effects. However, the underlying pathways are not yet clear. In this study, we first examined the effects of TDD on toll-like receptor-4 (TLR4) activity, the signaling receptor for lipopolysaccharide (LPS), and found that TDD does not inhibit LPS-induced TLR4 expression in EA.hy926 cells and the vascular wall in vivo. Next, we investigated the global protein alterations and the mechanisms underlying the action of TDD in LPS-treated EA.hy926 cells using an isobaric tag for the relative and absolute quantification technique. Western blot analysis revealed that TDD inhibited NF-κB activation by regulating the phosphorylation and subsequent degradation IκBα. Among the differentially expressed proteins, TDD concentration-dependently inhibited Caveolin 1(Cav1) expression. The interaction between Cav1 and TDD was determined by using biolayer interference assay, UV-vis absorption spectra, fluorescence spectrum, and molecular docking. We found that TDD can directly bind to Cav1 through hydrogen bonds and van der Waals forces. In conclusion, our results showed that TDD inhibited LPS-induced vascular inflammation and the NF-κB signaling pathway by specifically targeting the Cav1 protein. TDD may be a novel anti-inflammatory compound, especially for the treatment of atherosclerosis.
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影响因子：
29
作者：
Fernández-Hernando C;Yu J;Suárez Y;Rahner C;Dávalos A;Lasunción MA;Sessa WC
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影响因子：
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10.8
作者：
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9.8
作者：
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