title: (-)-Epicatechin-induced recovery of mitochondria from simulated diabetes: Potential role of endothelial nitric oxide synthase.
abstract: (-)-Epicatechin increases indicators associated with mitochondrial biogenesis in endothelial cells and myocardium. We investigated endothelial nitric oxide synthase involvement on (-)-epicatechin-induced increases in indicators associated with mitochondrial biogenesis in human coronary artery endothelial cells cultured in normal-glucose and high-glucose media, as well as to restore indicators of cardiac mitochondria from the effects of simulated diabetes. Here, we demonstrate the role of endothelial nitric oxide synthase on (-)-epicatechin-induced increases in mitochondrial proteins, transcription factors and sirtuin 1 under normal-glucose conditions. In simulated diabetes endothelial nitric oxide synthase function, mitochondrial function-associated and biogenesis-associated indicators were adversely impacted by high glucose, effects that were reverted by (-)-epicatechin. As an animal model of type 2 diabetes, 2-month old C57BL/6 mice were fed a high-fat diet for 16 weeks. Fasting and fed blood glucose levels were increased and NO plasma levels decreased. High-fat-diet-fed mice myocardium revealed endothelial nitric oxide synthase dysfunction, reduced mitochondrial activity and markers of mitochondrial biogenesis. The administration of 1 mg/kg (-)-epicatechin for 15 days by oral gavage shifted these endpoints towards control mice values. Results suggest that endothelial nitric oxide synthase mediates (-)-epicatechin-induced increases of indicators associated with mitochondrial biogenesis in endothelial cells. (-)-Epicatechin also counteracts the negative effects that high glucose or simulated type 2 diabetes has on endothelial nitric oxide synthase function.
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México D.F., Mexico Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Israel
authors.initials: I
authors.lastname: Ramírez-Sánchez
authors.affiliation: Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Alonso
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México D.F., Mexico Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Aldo
authors.initials: A
authors.lastname: Moreno-Ulloa
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México D.F., Mexico.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ceballos
authors.affiliation: Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA fvillarr@ucsd.edu.
authors.forename: Francisco
authors.initials: F
authors.lastname: Villarreal
mesh_terms: D000818:Animals; D002392:Catechin / Q000494:pharmacology*; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001678:Organelle Biogenesis; D010766:Phosphorylation; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D002392:Catechin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: (-)-Epicatechin; cardiomyocytes; diabetes; endothelial cells; endothelial nitric oxide synthase