title: The roles of hyperglycaemia and oxidative stress in the rise and collapse of the natural protective mechanism against vascular endothelial cell dysfunction in diabetes.
abstract: Vascular endothelial cell (VEC) dysfunction in diabetes has been associated with hyperglycaemia-induced intra- and extracellular glycation of proteins and to overproduction of glucose-derived free radicals. VEC protect their intracellular environment against an increased influx of glucose in face of hyperglycaemia by reducing the expression and plasma membrane abundance of their glucose transporter-1 (GLUT-1). We investigated the hypothesis that glucose-derived free radicals induce this down-regulatory mechanism in VEC, but proved the contrary. In fact, pro-oxidants significantly increased the expression and plasma membrane abundance of GLUT-1 and the rate of glucose transport in VEC while abolishing high-glucose-induced down-regulation of the hexose transport system. The resulting uncontrolled influx of glucose followed by overproduction of glucose-derived ROS further up-regulates the rate of glucose transport, and vice versa. This perpetuating glycoxidative stress finally leads to the collapse of the auto-regulatory protective mechanism and accelerates the development of dysfunctional endothelium in blood vessels.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Cohen
authors.forename: Y
authors.initials: Y
authors.lastname: Riahi
authors.forename: E
authors.initials: E
authors.lastname: Alpert
authors.forename: A
authors.initials: A
authors.lastname: Gruzman
authors.forename: S
authors.initials: S
authors.lastname: Sasson
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D003920:Diabetes Mellitus / Q000473:pathology* / Q000503:physiopathology*; D042783:Endothelial Cells / Q000473:pathology*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species