title: 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.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kun-Ling
authors.initials: KL
authors.lastname: Tsai
authors.forename: Li-Hsin
authors.initials: LH
authors.lastname: Chen
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.forename: Guang-Yuh
authors.initials: GY
authors.lastname: Chiou
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Chen
authors.forename: Hsiang-Yun
authors.initials: HY
authors.lastname: Chou
authors.forename: Liang-Kung
authors.initials: LK
authors.lastname: Chen
authors.forename: Hsiao-Yun
authors.initials: HY
authors.lastname: Chen
authors.forename: Tsan-Hung
authors.initials: TH
authors.lastname: Chiu
authors.forename: Chiou-Sheng
authors.initials: CS
authors.lastname: Tsai
authors.forename: Hsiu-Chung
authors.initials: HC
authors.lastname: Ou
authors.forename: Chung-Lan
authors.initials: CL
authors.lastname: Kao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D008077:Lipoproteins, LDL; D016328:NF-kappa B; C495137:OLR1 protein, human; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D014451:Ubiquinone; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D055372:AMP-Activated Protein Kinases; C024989:coenzyme Q10