TRB3, upregulated by ox-LDL, mediates human monocyte-derived macrophage apoptosis

Authors

  • Yuan-yuan Shang,

    1.  Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Ji’nan, China
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    • These authors contributed equally to this paper

  • Zhi-hao Wang,

    1.  Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Ji’nan, China
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    • These authors contributed equally to this paper

  • Li-ping Zhang,

    1.  Department of Anatomy, School of Medicine, Shandong University, Ji’nan, China
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  • Ming Zhong,

    1.  Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Ji’nan, China
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  • Yun Zhang,

    1.  Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Ji’nan, China
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  • Jing-ti Deng,

    1.  Department of Anatomy, School of Medicine, Shandong University, Ji’nan, China
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  • Wei Zhang

    1.  Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Ji’nan, China
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W. Zhang, Department of Cardiology, Qilu Hospital of Shandong University, Ji’nan 250012, China
Fax: +86 531 86169356
Tel: +86 531 82169339
E-mail: zhangweisdu@gmail.com
J.-t. Deng, Department of Anatomy, School of Medicine of Shandong University, Ji’nan 250012, China
Fax: +86 531 86169356
Tel: +86 531 88382093
E-mail: jingtideng@hotmail.com

Abstract

Tribble3 (TRB3), a mammalian homolog of Drosophila tribbles, slows cell-cycle progression, and its expression is increased in response to various stresses. The aim of this study was to investigate the role of the TRB3 gene in macrophage apoptosis induced by oxidized low-density lipoprotein (ox-LDL). We found that, in human monocyte-derived macrophages, TRB3 is upregulated by ox-LDL in a dose- and time-dependent manner. The cell viability of TRB3-overexpressing macrophages was decreased, but apoptosis was increased and the level of activated caspase-3 increased. Factorial analyses revealed no significant interaction between TRB3 overexpression and ox-LDL stimulation with respect to macrophage apoptosis. Furthermore, TRB3-silenced macrophages showed decreased apoptosis, and TRB3-silenced cells treated with ox-LDL showed significantly increased apoptosis. Silencing of TRB3 and ox-LDL stimulation showed significant interaction for macrophage apoptosis, suggesting that TRB3 knockdown resisted the macrophage apoptosis induced by ox-LDL. Therefore, TRB3 in part mediates the macrophage apoptosis induced by ox-LDL, which suggests that TRB3 might be involved in vulnerable atherosclerotic plaque progression.

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