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

Kun Ling Tsai, Li Hsin Chen, Shih Hwa Chiou, Guang-Yuh Chiou, Yu Chih Chen, Hsiang Yun Chou, Liang Kung Chen, Hsiao Yun Chen, Tsan Hung Chiu, Chiou Sheng Tsai, Hsiu Chung Ou, Chung Lan Kao*

*Corresponding author for this work

Research output: Contribution to journalArticle

64 Scopus citations

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 24h. 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.

Original languageEnglish
JournalMolecular Nutrition and Food Research
Volume55
Issue numberSUPPL. 2
DOIs
StatePublished - 1 Sep 2011

Keywords

  • AMPK
  • Co Q10
  • Inflammation
  • NADPH oxidase
  • OxLDL

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