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学科主题: 基础医学
题名:
Role of redox factor-1 in hyperhomocysteinemia-accelerated atherosclerosis
作者: Dai, Jing1; Li, Wenjing1; Chang, Lina1; Zhang, Zhenmin1; Tang, Chaoshu1; Wang, Nanping1; Zhu, Yi1; Wang, Xian1
关键词: homocysteine ; redox factor-1 ; monocytes ; atherosclerosis ; MCP-1
刊名: FREE RADICAL BIOLOGY AND MEDICINE
发表日期: 2006-11-15
DOI: 10.1016/j.freeradbiomed.2006.08.020
卷: 41, 期:10, 页:1566-1577
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Endocrinology & Metabolism
研究领域[WOS]: Biochemistry & Molecular Biology ; Endocrinology & Metabolism
关键词[WOS]: DNA-BINDING ACTIVITY ; MONOCYTE CHEMOATTRACTANT PROTEIN-1 ; VASCULAR SMOOTH-MUSCLE ; FACTOR-KAPPA-B ; OXIDATIVE STRESS ; DEFICIENT MICE ; NITRIC-OXIDE ; ENDOTHELIAL-CELLS ; EPITHELIAL-CELLS ; NAD(P)H OXIDASE
英文摘要:

Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. We have previously shown that homocysteine can induce monocyte chemoattractant protein-1 (MCP-1) secretion via reactive oxygen species (ROS) in human monocytes in vitro. In the present study, we investigated whether redox factor-1 (Ref-1) is involved in HHcy-accelerated atherosclerosis. We used a mild HHcy animal model, aortic roots and peritoneal macrophages were isolated for immunohistochemistry and Western blotting, from apoE(-/-) and C57BL/6J mice fed a high Hcy diet (1.8 g/L) for 4 or 12 weeks. Four-week HHcy apoE(-/-) mice showed more plaques and significantly increased immunostaining of Ref-1 and MCPI in foam cells, and HHcy mice showed enhanced Ref-1 expression in peritoneal macrophages. To explore the mediating mechanism, incubation with Hcy (100 mu M) increased Ref-1 protein level and translocation in human monocytes in vitro. In addition, Hcy-induced NADPH oxidase activity mediated the upregulation of Ref-1. Furthermore, overexpressed Ref-1 upregulated NF-kappa B and MCP-1 promoter activity, and antisense Ref-1 reduced Hcy-induced NF-kappa B DNA-binding activity and MCP-1 secretion. These data indicate that Hcy-induced ROS upregulate the expression and translocation of Ref-1 via NADPH oxidase, and then Ref-1 increases NF-kappa B activity and MCP-1 secretion in human monocytes/macrophages, which may accelerate the development of atherosclerosis. (c) 2006 Elsevier Inc. All rights reserved.

语种: 英语
WOS记录号: WOS:000241563000007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52686
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100083, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100083, Peoples R China

Recommended Citation:
Dai, Jing,Li, Wenjing,Chang, Lina,et al. Role of redox factor-1 in hyperhomocysteinemia-accelerated atherosclerosis[J]. FREE RADICAL BIOLOGY AND MEDICINE,2006,41(10):1566-1577.
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