Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways

• Published in: Journal of diabetes research 2016-01, Vol.2016 (2016), p.1-14
• Main Authors: Lin, Shing-Jong, Lin, Feng-Yen, Chen, Jia-Shiong, Li, Szu-Yuan, Huang, Po-Hsun, Lin, Chih-Pei, Tsai, Hsiao-Ya, Chen, J.-W.
• Format: Article
• Language: English
• Subjects: AMP-Activated Protein Kinases - metabolism; Apoptosis; Apoptosis - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Diabetes; Disease; Endothelial Progenitor Cells - drug effects; Endothelial Progenitor Cells - metabolism; Glucose; Glucose - pharmacology; Growth factors; Humans; Ischemia; Kinases; Laboratory animals; Lectins; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Metabolism; Mitochondria - metabolism; Nitric Oxide - metabolism; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Senescence; Signal Transduction - drug effects; Ubiquinone - analogs & derivatives; Ubiquinone - pharmacology
• ISSN: 2314-6745; 2314-6753
• DOI: 10.1155/2016/6384759

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) enviroment 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.