title: Dehydroepiandrosterone inhibits the activation and dysfunction of endothelial cells induced by high glucose concentration.
abstract: Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes; however, its mechanisms of action are unknown. Here, we focus on the effect of DHEA on the activation of endothelial cells induced by a high concentration of glucose. Adhesion on U937 cells, expression of adhesion molecules, production of ROS and NO, expression of eNOS, and translocation of NF-κB were evaluated in human umbilical vein endothelial cells (HUVEC) treated with high concentrations of glucose, DHEA, or both. High concentrations of glucose (>20mM) induced an increase in adhesion, an increment in mainly E-selectin and PECAM-1 expression, as well as in ROS and NO production, eNOS expression, translocation of NF-κB, and degradation of its inhibitor IκB-α. DHEA abolished adhesion and the increase of E-selectin, ICAM-1, VCAM-1, and PECAM-1 induced by glucose. In addition, DHEA completely blocked oxidative stress and decreased translocation of NF-κB and the degradation of IκB-α induced by glucose. These results suggest that DHEA protects against the activation of endothelial cells induced by high concentrations of glucose, indicating that DHEA could be useful in the treatment of hyperglycemia and diabetes.
authors.affiliation: Departamento de Biología Celular, Instituto Nacional de Cardiología Ignacio Chávez, Mexico DF, Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Huerta-García
authors.forename: José Luis
authors.initials: JL
authors.lastname: Ventura-Gallegos
authors.forename: Maria Elena Crescencio
authors.initials: ME
authors.lastname: Victoriano
authors.forename: Angélica
authors.initials: A
authors.lastname: Montiél-Dávalos
authors.forename: Gerardo
authors.initials: G
authors.lastname: Tinoco-Jaramillo
authors.forename: Rebeca
authors.initials: R
authors.lastname: López-Marure
mesh_terms: D002448:Cell Adhesion; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D019040:E-Selectin / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005947:Glucose / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D019040:E-Selectin; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017382:Reactive Oxygen Species; C546936:SELE protein, human; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D003687:Dehydroepiandrosterone; D005947:Glucose