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Regulatory role of thioredoxin in homocysteine-induced monocyte chemoattractant protein-1 secretion in monocytes/macrophages |
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| Authors: | Dai Jing Wang Xiaofei Feng Juan Kong Wei Xu Qingbo Shen Xun Wang Xian |
| Affiliation: | a Department of Physiology and Pathophysiology, School of Basic Medical Science, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100083, P.R. China b Cardiovascular Division, The James Black Centre, Kings College London, London SE5 9NU, UK c Institute of Biophysics, Chinese Academy of Sciences, Beijing, P.R. China |
| Abstract: | We have previously shown that homocysteine (Hcy) can induce monocyte chemoattractant protein-1 (MCP-1) secretion via reactive oxygen species (ROS) in human monocytes. Here, we show that Hcy upregulates expression of an important antioxidative protein, thioredoxin (Trx), via NADPH oxidase in human monocytes in vitro. The increase of Trx expression and activity inhibited Hcy-induced ROS production and MCP-1 secretion. Of note, 2-week hyperhomocysteinemia (HHcy) ApoE−/− mice showed accelerated lesion formation and parallel lower Trx expression in macrophages than ApoE−/− mice, suggesting that HHcy-induced sustained oxidative stress in vivo might account for impaired Trx and hence increased ROS production and MCP-1 secretion from macrophages, and subsequently accelerated atherogenesis. |
| Keywords: | Trx, thioredoxin MCP-1, monocyte chemoattractant protein-1 ROS, reactive oxygen species Hcy, homocysteine HHcy, hyperhomocysteinemia |
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