Regulatory role of thioredoxin in homocysteine-induced monocyte chemoattractant protein-1 secretion in monocytes/macrophages

Dai, Jing; Wang, Xiaofei; Feng, Juan; Kong, Wei; Xu, Qingbo; Shen, Xun; Wang, Xian

doi:10.1016/j.febslet.2008.10.030

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Volume 582, Issue 28 , Pages 3893-3898, 26 November 2008

Regulatory role of thioredoxin in homocysteine-induced monocyte chemoattractant protein-1 secretion in monocytes/macrophages

Edited by Stuart Ferguson

Jing Dai
- 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
- J. Dai and X. Wang contributed equally to this work.
- Present address: Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Xiaofei Wang
- 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
- J. Dai and X. Wang contributed equally to this work.
Juan Feng
- 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
Wei Kong
- 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
Qingbo Xu
- Cardiovascular Division, The James Black Centre, Kings College London, London SE5 9NU, UK
Xun Shen
- Institute of Biophysics, Chinese Academy of Sciences, Beijing, P.R. China
Xian Wang
- 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
- Corresponding author. Fax: +86 10 82801443.

Received 7 October 2008; received in revised form 17 October 2008; accepted 17 October 2008. published online 29 October 2008.

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.

Abbreviations: Trx, thioredoxin, MCP-1, monocyte chemoattractant protein-1, ROS, reactive oxygen species, Hcy, homocysteine, HHcy, hyperhomocysteinemia