Advanced oxidation protein products activate vascular endothelial cells via a RAGE-mediated signaling pathway
Advanced oxidation protein products activate vascular endothelial cells via a RAGE-mediated signaling pathway
复制标题
高级氧化蛋白产品通过 RAGE 介导的信号通路激活血管内皮细胞
DOI：
10.1089/ars.2007.1999
复制
发表时间：
2008-10-01
影响因子：
6.6
通讯作者：
Zhang, Xun
中科院分区：
文献类型：
--
作者：
Guo, Zhi Jian;Niu, Hong Xin;Zhang, Xun
晚期氧化蛋白产物（AOPPs）的积累与糖尿病、慢性肾功能不全和动脉粥样硬化中的血管病变有关。然而，参与aopps诱导的内皮细胞（ECs）扰动的信号通路是未知的，并进行了研究。AOPPs修饰的人血清白蛋白（AOPPs- hsa）以剂量依赖和饱和的方式与晚期糖基化终产物（RAGE）受体结合。AOPPs-HSA竞争性地抑制可溶性RAGE （sRAGE）与其优先配体晚期糖基化终产物（AGEs）的结合。体外制备或从尿毒症血清中分离的AOPPs与人脐静脉ECs孵育，诱导超氧化物的产生、NAD(P) H氧化酶、ERK 1/2和p38的激活以及NF-kappa b的核易位。AOPPs-ECs相互作用激活信号通路，导致VCAM-1和ICAM-1在基因和蛋白水平上过表达。这种由aopps引发的ECs生化级联反应可以通过抗RAGE IgG或过量的sRAGE阻断RAGE来阻止，但不受中和性抗age IgG的影响。这些数据提示AOPPs可能是内皮RAGE的新配体。AOPPs-HSA通过rage介导的信号激活血管内皮细胞。
The accumulation of advanced oxidation protein products (AOPPs) has been linked to vascular lesions in diabetes, chronic renal insufficiency, and atherosclerosis. However, the signaling pathway involved in AOPPs-induced endothelial cells (ECs) perturbation is unknown and was investigated. AOPPs modified human serum albumin (AOPPs-HSA) bound to the receptor for advanced glycation end products (RAGE) in a dose-dependent and saturable manner. AOPPs-HSA competitively inhibited the binding of soluble RAGE (sRAGE) with its preferential ligands advanced glycation end products (AGEs). Incubation of AOPPs, either prepared in vitro or isolated from uremic serum, with human umbilical vein ECs induced superoxide generation, activation of NAD(P) H oxidase, ERK 1/2 and p38, and nuclear translocation of NF-kappa B. Activation of signaling pathway by AOPPs-ECs interaction resulted in overexpression of VCAM-1 and ICAM-1 at both gene and protein levels. This AOPPs-triggered biochemical cascade in ECs was prevented by blocking RAGE with either anti-RAGE IgG or excess sRAGE, but was not affected by the neutralizing anti-AGEs IgG. These data suggested that AOPPs might be new ligands of endothelial RAGE. AOPPs-HSA activates vascular ECs via RAGE-mediated signals.