Characterization of the hepatic cellular uptake of α_1-acid glycoprotein (AGP), Part 2 : Involvement of the hemoglobin β-chain on plasma membranes in the uptake of human AGP by liver parenchymal cells
Characterization of the hepatic cellular uptake of α_1-acid glycoprotein (AGP), Part 2 : Involvement of the hemoglobin β-chain on plasma membranes in the uptake of human AGP by liver parenchymal cells
复制标题
肝细胞摄取 α_1-酸性糖蛋白 (AGP) 的特征，第 2 部分：质膜上的血红蛋白 β 链参与肝实质细胞摄取人 AGP
DOI：
10.1002/jps.22804
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发表时间：
2011
影响因子：
3.8
通讯作者：
小森久和
中科院分区：
文献类型：
--
作者：
西弘二;小森久和;小森久和
人α1-酸性糖蛋白（AGP）是一种血清糖蛋白，已知具有抗炎活性。我们最近报道，AGP主要通过受体介导的途径被纳入小鼠的肝脏，尽管其机制在很大程度上是未知的。本研究的目的是鉴定识别AGP肽部分的特异性细胞表面蛋白。111 In-AGP和111 In-重组聚糖缺陷型AGP（rAGP）在小鼠体内的药代动力学研究表明，两种AGP主要分布于肝脏和肾脏，但rAGP的肝脏和肾脏摄取清除率高于AGP。rAGP的肝脏摄取被抑制在存在下的100倍过量的未标记的AGP，表明rAGP的肝脏摄取共享一个共同的途径与AGP，它承认的肽部分的AGP。在使用小鼠肝脏的粗细胞膜部分的配体印迹分析中，观察到对应于16 kDa蛋白质的条带与两种AGP结合。有趣的是，基质辅助激光解吸电离飞行时间质谱MALDI-TOF-MS和蛋白质印迹分析表明，这16 kDa的蛋白质是血红蛋白β链（HBB）。因此，六溴代二苯似乎通过与其肽部分的直接相互作用与肝摄取AGP有关。
Humanα1-acid glycoprotein (AGP), a serum glycoprotein, is known to have anti-inflammatory activity. We recently reported that AGP was mainly incorporated into the liver in mice via a receptor-mediated pathway, although the mechanism for this was largely unknown. The objective of this study was to identify the specific cellular surface protein that recognizes the peptide moiety of AGP. Pharmacokinetic studies of111In–AGP and111In –recombinant glycan-deficient AGP (rAGP) in mice demonstrated that both AGPs are mainly distributed to the liver and kidney, but hepatic and renal uptake clearance of rAGP was higher than that for AGP. Hepatic uptake of rAGP was inhibited in the presence of 100-fold excess of unlabeled AGP, indicating that the hepatic uptake of rAGP shared a common route with that of AGP and that it recognized the peptide moiety of AGPs. In ligand blotting analyses using crude cellular membrane fraction of mice liver, a band corresponding to a 16 kDa protein was observed to bind to both AGPs. Interestingly, matrix-assisted laser desorption ionization–time-of-flight mass spectrometry MALDI–TOF-MS and western blotting analyses indicated that this 16 kDa protein is the hemoglobinβ-chain (HBB). It, therefore, appears that HBB is associated with the hepatic uptake of AGP via a direct interaction with its peptide moiety.