The role of reactive oxygen species in TNFα-dependent expression of the receptor for advanced glycation end products in human umbilical vein endothelial cells
The role of reactive oxygen species in TNFα-dependent expression of the receptor for advanced glycation end products in human umbilical vein endothelial cells
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DOI：
10.1016/j.bbamcr.2005.03.007
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发表时间：
2005-06-30
影响因子：
5.1
通讯作者：
Hoidal, JR
中科院分区：
文献类型：
--
作者：
Mukherjee, TK;Mukhopadhyay, S;Hoidal, JR
晚期糖基化终末产物受体（receptor for advanced glycation end products，RECEPTOR）通过其信号转导配体参与动脉粥样硬化的发生和发展。TNF α是一种促炎细胞因子，是内皮细胞中TNF α表达的有效诱导剂。在本研究中，我们证明了由TNF α刺激的人脐静脉内皮细胞（HUVECs）产生的活性氧（ROS）诱导TNF α表达。线粒体呼吸链复合体III似乎是ROS的主要来源。NADPH氧化酶的gp 91 phox亚基似乎是ROS的来源，其诱导TNF α依赖性线粒体ROS产生和随后的TNF α表达。我们还证明ROS介导的炎症诱导是通过激活NF-κ B（一种促炎转录因子）而发生的。因此，TNF α刺激HUVEC会引发以下事件顺序：刺激NADPH氧化酶-->产生活性氧-->激活线粒体呼吸链-->刺激NF-κ B活性-->诱导RAGE表达。(C)2005 Elsevier B. V.保留所有权利。
Engagement of the receptor for advanced glycation end products (RAGE) by its signal transduction ligands is implicated in the development and progression of atherosclerosis. TNF alpha, a proinflammatory cytokine, is a potent inducer of RAGE expression in endothelial cells. In the present study, we demonstrate that reactive oxygen species (ROS) generated by TNF alpha stimulated human umbilical vein endothelial cells (HUVECs) induce RAGE expression. The complex III of mitochondrial respiratory chain appears to be the primary source of ROS. The gp91phox subunit of NADPH oxidase appears to be the source of ROS that induces TNF alpha-dependent mitochondrial ROS generation and subsequent RAGE expression. We also demonstrate that the ROS-mediated RAGE induction occurs via activation of NF-kappa B, a proinflammatory transcription factor. Thus, stimulation of HUVECs by TNF alpha evokes the following sequence of events: stimulation of NADPH oxidase --> generation of ROS --> activation of the mitochondrial respiratory chain --> stimulation of NF-kappa B activity --> induction of RAGE expression. (C) 2005 Elsevier B.V.All rights reserved.