title: Cyanidin-3-O-glucoside modulates intracellular redox status and prevents HIF-1 stabilization in endothelial cells in vitro exposed to chronic hypoxia.
abstract: The term hypoxia refers to conditions characterized by a relative restriction of oxygen supply. It is usually associated to a paradoxical overproduction of reactive oxygen species (ROS) and to the activation of several transcription factors, including HIF-1α, which in turn trigger angiogenic and apoptotic response. In this study we have investigated the mechanisms by which the anthocyanin cyanidin-3-O-glucoside (C3G) modulates hypoxia induced response in human endothelial cells (HUVECs). In fact, hypoxia induces an increase of ROS generation in HUVECs paralleled by a loss of antioxidant cellular capacity. According to the observed increase of HO-1 mRNA expression, pretreatment of C3G to HUVEC reduces the entity of oxidative stress thanks to the activation of cellular antioxidant response. C3G also attenuates HIF-1α protein accumulation conditions supporting the hypothesis of a major role of oxidative stress in the presence of low oxygen. Furthermore, the increased expression of angiogenesis and apoptosis markers (MMP-2 and caspase-3) due to HIF-1α activation by hypoxia is reduced in C3G pretreated cells. Overall, our data suggest that the modulation of intracellular redox status induced by C3G may be an important protective mechanism against endothelial damage in hypoxic conditions.
authors: Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors: S
authors: S
authors: Anwar
authors: Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors: A
authors: A
authors: Speciale
authors: Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors: D
authors: D
authors: Fratantonio
authors: Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors: M
authors: M
authors: Cristani
authors: Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors: A
authors: A
authors: Saija
authors: Agricultural Research Council - Food and Nutrition Research Centre (C.R.A. - NUT), Via Ardeatina 546, 00178 Rome, Italy.
authors: F
authors: F
authors: Virgili
authors: Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy. Electronic address: fcimino@unime.it.
authors: F
authors: F
authors: Cimino
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D055550:Protein Stability; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D000975:Antioxidants; D005960:Glucosides; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; C462279:cyanidin-3-O-beta-glucopyranoside; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C505407:CASP3 protein, human; D053148:Caspase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Cellular adaptive response; Cyanidin; Endothelial dysfunction; Hypoxia; Nrf2; Oxidative stress