S100 protein translocation in response to extracellular S100 is mediated by receptor for advanced glycation endproducts in human endothelial cells
S100 protein translocation in response to extracellular S100 is mediated by receptor for advanced glycation endproducts in human endothelial cells
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DOI：
10.1016/j.bbrc.2004.02.135
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发表时间：
2004-04-09
影响因子：
3.1
通讯作者：
Heizmann, CW
中科院分区：
文献类型：
--
作者：
Hsieh, HL;Schäfer, BW;Heizmann, CW
近年来，这100种蛋白的细胞外功能引起了越来越多的关注。s100蛋白是一组钙结合蛋白，具有细胞和组织特异性表达，在不同病理条件下观察到该家族成员的不同表达水平。已报道的S100蛋白的细胞外功能包括增强神经突生长、参与炎症和肿瘤细胞运动的能力。在我们之前的研究中，我们报道了S100A13易位，以响应血管紧张素II诱导的细胞内钙水平升高。为了研究细胞外S100A13的潜在作用，本研究使用重组S100A13刺激人内皮细胞。向细胞中添加细胞外S100A13可导致内源性蛋白质易位和从细胞外空间摄取蛋白质。为了测试这种效应的特异性，还添加了各种其他S100蛋白。有趣的是，只有当细胞受到相同的细胞外S100蛋白刺激时，才会观察到特定S100蛋白的易位。由于晚期糖基化终产物受体（RAGE）被认为是S100蛋白的细胞表面受体，并参与多种信号转导途径，我们接下来研究了受体与细胞外S100蛋白之间的相互作用。我们在这里表明，在RAGE介导的转导途径中，作为下游调节因子的NF-kappaB可以通过添加细胞外S100蛋白而被激活，并且S100蛋白的易位被可溶性RAGE抑制。这些实验表明，尽管细胞外S100蛋白诱导的细胞内易位是特异性的，但内皮细胞上的S100蛋白有一个共同的细胞表面受体。(C) 2004爱思唯尔公司版权所有。
The extracellular functions of's 100 proteins have attracted more attention in recent years. S 100 proteins are a group of calcium-binding proteins which exhibit cell- and tissue-specific expression, and different expression levels of members from this family have been observed in various pathological conditions. The reported extracellular functions of S100 proteins include the ability to enhance neurite outgrowth, involvement in inflammation, and motility of tumour cells. In our previous study, we reported translocation of S100A13 in response to the elevated intracellular calcium levels induced by angiotensin II. In order to investigate potential effects of extracellular S100A13, recombinant S100A13 was used here to stimulate human endothelial cells. Addition of extracellular S100A13 to the cells resulted in both endogenous protein translocation and protein uptake from the extracellular space. To test specificity of this effect, addition of various other S100 proteins was also performed. Interestingly, translocation of specific S100 proteins was only observed when the cells were stimulated with the same extracellular S100 protein. Since the receptor for advanced glycation end products (RAGE) is a putative cell Surface receptor for S100 proteins and is involved in various signal transduction pathways, we next investigated the interaction between the receptor and extracellular S100 proteins. We show here that NF-kappaB which is a downstream regulator in RAGE-mediated transduction pathways can be activated by addition of extracellular S100 proteins, and translocation of S100 proteins was inhibited by soluble RAGE. These experiments suggest a common cell surface receptor for S100 proteins on endothelial cells even though intracellular translocation induced by extracellular S100 proteins is specific. (C) 2004 Elsevier Inc. All rights reserved.