title: Nanomolar Caffeic Acid Decreases Glucose Uptake and the Effects of High Glucose in Endothelial Cells.
abstract: Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG). In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels. Moreover, caffeic acid countered HG-induced loss of barrier integrity, reducing actin rearrangement and FITC-dextran passage. The decreased flux of glucose associated to caffeic acid affected HG induced apoptosis by down-regulating the expression of initiator (caspase 8 and 9) and effector caspases (caspase 7 and 3) and by increasing the levels of phosphorylated Bcl-2. We also observed that caffeic acid in HG condition was associated to a reduction of p65 subunit nuclear levels with respect to HG alone. NF-κB activation has been shown to lead to apoptosis in HG treated cells and the analysis of the expression of a panel of about 90 genes related to NF-κB signaling pathway revealed that caffeic acid significantly influenced gene expression changes induced by HG. In conclusion, our results suggest that caffeic acid, decreasing the metabolic stress induced by HG, allows the activation of survival mechanisms mediated by a different modulation of NF-κB-related signaling pathways and to the activation of anti-apoptotic proteins.
authors.affiliation: Council for Agricultural Research and Economics, Food and Nutrition Research Centre, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Natarelli
authors.affiliation: Council for Agricultural Research and Economics, Food and Nutrition Research Centre, Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ranaldi
authors.affiliation: Department of Physics, Sapienza University of Rome, Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Leoni
authors.affiliation: Council for Agricultural Research and Economics, Food and Nutrition Research Centre, Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Roselli
authors.affiliation: Council for Agricultural Research and Economics, Food and Nutrition Research Centre, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Guantario
authors.affiliation: Council for Agricultural Research and Economics, Food and Nutrition Research Centre, Rome, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Comitato
authors.affiliation: Council for Agricultural Research and Economics, Food and Nutrition Research Centre, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ambra
authors.affiliation: Department of Drug Sciences and Health Products, University of Messina, Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cimino
authors.affiliation: Department of Drug Sciences and Health Products, University of Messina, Messina, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Speciale
authors.affiliation: Council for Agricultural Research and Economics, Food and Nutrition Research Centre, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Virgili
authors.affiliation: Council for Agricultural Research and Economics, Food and Nutrition Research Centre, Rome, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Canali
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D051272:Glucose Transporter Type 1; D016328:NF-kappa B; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; D005947:Glucose; C040048:caffeic acid