title: Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways.
abstract: Coenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) environment for 3 days, followed by treatment with CoQ10 (10 μM) for 24 hr. Cell proliferation, nitric oxide (NO) production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsiao-Ya
authors.initials: HY
authors.lastname: Tsai
authors.affiliation: Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan ; Department of Biotechnology and Laboratory Science in Medicine and Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chih-Pei
authors.initials: CP
authors.lastname: Lin
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan ; Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan ; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Huang
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan ; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Szu-Yuan
authors.initials: SY
authors.lastname: Li
authors.affiliation: Institute and Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jia-Shiong
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Feng-Yen
authors.initials: FY
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan ; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan ; Institute and Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan ; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan ; Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan ; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan ; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D014451:Ubiquinone; D009569:Nitric Oxide; D055372:AMP-Activated Protein Kinases; C024989:coenzyme Q10; D005947:Glucose