Inhibitory effect of GSPE on RAGE expression induced by advanced glycation end products in endothelial cells.
Advanced glycation end products' (AGEs) engagement of a cell-surface receptor for AGEs (RAGE) has been causally implicated in the pathogenesis of diabetic vascular complications via induction of reactive oxygen species (ROS) and subsequent alteration of many gene expressions, including RAGE itself. Grapeseed proanthocyanidin extract (GSPE), which is a naturally occurring polyphenolic compound, has been reported to possess potent radical-scavenging and antioxidant properties and to display significant cardiovascular protective action. In this study, we investigated whether GSPE could inhibit AGE-induced RAGE expression through interference with ROS generation in human umbilical-vein endothelial cells (HUVECs). AGE-modified bovine serum albumin (AGE-BSA) was prepared by incubating BSA with high-concentration glucose. Stimulation of cultured HUVECs with 200 microg/mL of AGE-BSA significantly enhanced intracellular ROS formation and subsequently upregulated the protein and mRNA expression of RAGE; unmodified BSA and GSPE alone had no effect. However, GSPE preincubation markedly downregulated AGE-induced surface expression of RAGE in a time- and concentration-dependent manner. In AGE-stimulated HUVECs, GSPE also dose-dependently decreased RAGE mRNA levels and inhibited AGE-induced ROS generation at defined time periods. These results demonstrate that GSPE can inhibit enhanced RAGE expression in AGE-exposed endothelial cells by suppressing ROS generation, thereby limiting the AGE-RAGE interaction. Hence, GSPE may have therapeutic potential in the prevention and treatment of vascular complications in diabetic patients.
Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, China.
Feng-Lei
FL
Zhang
Hai-Qing
HQ
Gao
Lin
L
Shen
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D056604:Grape Seed Extract; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D000975:Antioxidants; D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D010936:Plant Extracts; D044945:Proanthocyanidins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine