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Coenzyme Q10 suppresses oxLDL-induced endothelial oxidative injuries by the modulation of LOX-1-mediated ROS generation via the AMPK/PKC/NADPH oxidase signaling pathway

Authors

  • Kun-Ling Tsai,

    1. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
    2. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan
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  • Li-Hsin Chen,

    1. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan
    2. Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan
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  • Shih-Hwa Chiou,

    1. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
    2. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan
    3. Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan
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  • Guang-Yuh Chiou,

    1. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan
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  • Yu-Chih Chen,

    1. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan
    2. Insitute and Hospital and Health Care administration, National Yang-Ming Unicersity, Taipei, Taiwan
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  • Hsiang-Yun Chou,

    1. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan
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  • Liang-Kung Chen,

    1. Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan
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  • Hsiao-Yun Chen,

    1. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
    2. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan
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  • Tsan-Hung Chiu,

    1. Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan
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  • Chiou-Sheng Tsai,

    1. Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
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  • Hsiu-Chung Ou,

    1. Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan
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    • These authors contributed equally to this work.

  • Chung-Lan Kao

    Corresponding author
    1. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
    2. Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan
    • Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 11217, Taiwan Fax: +886-2-28757359
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    • These authors contributed equally to this work.


Abstract

Scope: The lectin-like oxidized low-density lipoprotein receptor (LOX-1) is one pivot receptor for oxidized low-density lipoprotein (oxLDL) in human endothelial cells. Co-enzyme Q10 (Co Q10) has been widely used in clinical intervention. However, the molecular mechanisms underlying its protective effects against oxidative stress in endothelial cells are still largely unknown. This study was designed to test the hypothesis that Co Q10 mitigates oxLDL-induced endothelial oxidative injuries via modulation of LOX-1-mediated reactive oxygen species (ROS) generation and explored the role of AMP-activated protein kinase (AMPK), a negative regulator of NADPH oxidase.

Methods and results: Human umbilical vein endothelial cells (HUVECs) were pretreated with Co Q10 and then incubated with oxLDL for 24 h. Co Q10 attenuated oxLDL-elicited LOX-1 expression and ROS generation by suppression of NADPH oxidase activation. Co Q10 rescued dephosphorylation of AMPK caused by oxLDL that in turn led to an activation of NADPH oxidase by PKC. The results were confirmed using AMPK siRNA. Moreover, oxLDL-suppressed Akt/eNOS and enhanced p38 phosphorylation, which in turn activated NF-κB pathway. These detrimental events were ameliorated by Co Q10.

Conclusion: These results provide new highlight onto the possible molecular mechanisms of how Q10 suppresses oxLDL-induced endothelial oxidative injuries by the modulation of LOX-1-mediated ROS generation via the AMPK/PKC/NADPH oxidase signaling pathway.

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