Purification and characterization of mouse soluble receptor for advanced glycation end products (sRAGE)

Purification and characterization of mouse soluble receptor for advanced glycation end products (sRAGE)
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DOI:
10.1074/jbc.m409782200
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发表时间:
2004-11-26
影响因子:
4.8
通讯作者:
Oury, TD
Oury, TD
中科院分区:
生物学2区
文献类型:
--
作者:
Hanford, LE;Enghild, JJ;Oury, TD

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晚期糖基化终产物受体(receptor for advanced glycation end products,AGEs)是细胞表面蛋白免疫球蛋白超家族的一员,在从慢性炎症到癌症再到阿尔茨海默病的许多病理状态中起着进展因子的作用。在这种情况下,细菌会促进致病过程。其分泌的同种型,可溶性β-淀粉样蛋白或可溶性β-淀粉样蛋白,具有通过充当诱饵来阻止β-淀粉样蛋白信号传导的能力。Sodium已成功地用于一系列疾病的动物模型中,以拮抗RAGE介导的病理过程。在人类中,sleep是由sleep mRNA的选择性剪接引起的。本研究的目的是确定是否同样适用于小鼠safening,此外,生化表征小鼠safening。检查的生化特征包括糖基化和二硫键模式。此外,发现sodium结合肝素,这可能介导其在细胞外基质和组织细胞表面的分布。最后,我们的数据表明,在小鼠中的剪接可能是由羧基末端截短,在人类中报道的选择性剪接机制相反。
The receptor for advanced glycation end products ( RAGE) is a member of the immunoglobulin superfamily of cell surface proteins that has been implicated as a progression factor in a number of pathologic conditions from chronic inflammation to cancer to Alzheimer's disease. In such conditions, RAGE acts to facilitate pathogenic processes. Its secreted isoform, soluble RAGE or sRAGE, has the ability to prevent RAGE signaling by acting as a decoy. sRAGE has been used successfully in animal models of a range of diseases to antagonize RAGE-mediated pathologic processes. In humans, sRAGE results from alternative splicing of RAGE mRNA. This study was aimed to determine whether the same holds true for mouse sRAGE and, in addition, to biochemically characterize mouse sRAGE. The biochemical characteristics examined include glycosylation and disulfide patterns. In addition, sRAGE was found to bind heparin, which may mediate its distribution in the extracellular matrix and cell surfaces of tissues. Finally, our data indicated that sRAGE in the mouse is likely produced by carboxyl-terminal truncation, in contrast to the alternative splicing mechanism reported in humans.