首页> 外文期刊>Oxidative Medicine and Cellular Longevity >Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2
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Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2

机译:通过抑制Akt Ser473磷酸化和纤溶酶原激活剂抑制剂-2的下调,诱导巨噬细胞凋亡诱导巨噬细胞凋亡,Apigenin通过诱导巨噬细胞凋亡衰减

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Macrophage survival is believed to be a contributing factor in the development of early atherosclerotic lesions. Dysregulated apoptosis of macrophages is involved in the inflammatory process of atherogenesis. Apigenin is a flavonoid that possesses various clinically relevant properties such as anti-inflammatory, antiplatelet, and antitumor activities. Here we showed that apigenin attenuated atherogenesis inapoE-/-mice in anin vivotest.In vitroexperiments suggested that apigenin induced apoptosis of oxidized low density lipoprotein- (OxLDL-) loaded murine peritoneal macrophages (MPMs). Proteomic analysis showed that apigenin reduced the expression of plasminogen activator inhibitor 2 (PAI-2). PAI-2 has antiapoptotic effects in OxLDL-loaded MPMs. Enhancing PAI-2 expression significantly reduced the proapoptosis effects of apigenin. Molecular docking assay with AutoDock software predicted that residue Ser473 of Akt1 is a potential binding site for apigenin. Lentiviral-mediated overexpression of Akt1 wild type weakened the proapoptosis effect of apigenin in OxLDL-loaded MPMs. Collectively, apigenin executes its anti-atherogenic effects through inducing OxLDL-loaded MPMs apoptosis. The proapoptotic effects of apigenin were at least partly attributed to downregulation of PAI-2 through suppressing phosphorylation of AKT at Ser473.
机译:据信巨噬细胞存活是早期动脉粥样硬化病变的发展中的贡献因素。巨噬细胞的失调凋亡涉及血液发生的炎症过程。 Apigenin是一种类黄酮,具有各种临床相关性质,如抗炎,抗血小板和抗肿瘤活性。在这里,我们展示了AninVivotest中的Apigenin减毒α-/ - 小鼠inapoe-/ - 小鼠。体育实验表明,Apigenin诱导氧化低密度脂蛋白 - (OXLDL-)载荷的鼠腹膜巨噬细胞(MPMS)的凋亡。蛋白质组学分析表明,Apigenin降低了纤溶酶原激活物抑制剂2(PAI-2)的表达。 PAI-2在OXLDL加载的MPM中具有抗涂层效应。增强PAI-2表达显着降低了Apigenin的促凋亡作用。用Autodock软件的分子对接测定预测Akt1的残留物Ser473是磷酸蛋白的潜在结合位点。慢病毒介导的AKT1野生型过表达削弱了oxldl负载MPMS中Apigenin的促凋亡作用。统称,Apigenin通过诱导oxldl加载的MPM凋亡来执行其抗动脉粥样菌。通过在SER473抑制AKT的磷酸化,Apigenin对Pai-2的下调至少部分归因于PAI-2的下调。

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