title: N-Epsilon-(carboxymethyl)lysine is unable to induce endothelial dysfunction but is able to attenuate Ages-induced endothelium damage in human umbilical vein endothelial cells.
abstract: N-Epsilon-carboxymethyllysine (CML), one of the main compounds in advanced glycation end products (AGEs), has been thought to be a high bioaffinity ligand of the receptor for AGEs (RAGE), and is involved in the pathogenesis in endothelial dysfunction in diabetic vascular complications. However, some researchers believed that CML was unable to bind to RAGE and could not induce endothelium damage. In our present experiment, the role of CML in inducing endothelial dysfunction, preventing AGEs-induced damage and binding to RAGE was explored in human umbilical vein endothelial cells (HUVECs). The treatment with CML could not induce the endothelial dysfunction by itself, including upregulation on transforming growth factor-betai (TGF-beta1), intercellular adhesion molecule-1 (ICAM-1) and RAGE proteins expressions, apoptosis and cell viability in HUVECs. However, pretreatment with CML could attenuate AGEs-induced endothelial dysfunction. Fluorescence polarization assay showed that CML had a bioaffinity to RAGE. The IC50 of CML binding to RAGE (10 ng and 100 ng) were 7.133 x 10-8M and 1.563 x 10-6M, respectively. Our findings indicate that CML has no cytotoxic injury to endothelium but has a bioaffinity for the binding to RAGE.
authors.affiliation: Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, P.R. China. wenmoxiushi@163.com
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.forename: Mao-Mao
authors.initials: MM
authors.lastname: Zhu
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Zhang
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Jia
mesh_terms: D000165:Acridine Orange; D000328:Adult; D000465:Algorithms; D017209:Apoptosis / Q000187:drug effects; D003627:Data Interpretation, Statistical; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects*; D004996:Ethidium; D005260:Female; D005454:Fluorescence Polarization; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011247:Pregnancy; D013778:Tetrazolium Salts; D013844:Thiazoles; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D017127:Glycation End Products, Advanced; D013778:Tetrazolium Salts; D013844:Thiazoles; D053773:Transforming Growth Factor beta1; D018799:Intercellular Adhesion Molecule-1; C048496:N(6)-carboxymethyllysine; D004996:Ethidium; C022616:thiazolyl blue; D000165:Acridine Orange; D008239:Lysine