title: Glucagon-like peptide-1 attenuates advanced oxidation protein product-mediated damage in islet microvascular endothelial cells partly through the RAGE pathway.
abstract: Advanced oxidation protein products (AOPPs) are knownt to play a role in the pathogenesis of diseases and related complications. However, whether AOPPs affect the survival of islet microvascular endothelial cells (IMECs) has not been reported to date, at least to the best of our knowledge. In this study, we aimed to investigate the mechanisms underlying AOPP-mediated damage in IMECs and the protective role of glucagon-like peptide-1 (GLP-1), which has been suggested to exert beneficial effects on the cardiovascular system. IMECs were treated with AOPPs (0-200 µg/ml) for 0-72 h in the presence or absence of GLP-1 (100 nmol/l). Apoptosis, cell viability and reactive oxygen species (ROS) production were examined, the expression levels of p53, Bax, receptor for advanced glycation end-products (RAGE) and NAD(P)H oxidase subunit were determined, and the activity of NAD(P)H oxidase, caspase-9 and caspase-3 was also determined. The results revealed that AOPPs increased the expression of RAGE, p47phox and p22phox; induced NAD(P)H oxidase-dependent ROS generation, increased p53 and Bax expression, enhanced the activity of caspase-9 and caspase-3, and induced cell apoptosis. Treatment with GLP-1 decreased the expression of RAGE, inhibited NAD(P)H oxidase activity, decreased cell apoptosis and increased cell viability. On the whole, our findings indicate that AOPPs induce the apoptosis of IMECs via the RAGE-NAD(P)H oxidase-dependent pathway and that treatment with GLP-1 effectively reverses these detrimental effects by decreasing AOPP-induced RAGE expression and restoring the redox balance. Our data may indicate that GLP-1 may prove to be beneficial in attenuating the progression of diabetes mellitus.
authors: Department of Endocrinology, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors: Zhen
authors: Z
authors: Zhang
authors: Department of Nephrology, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors: Lei
authors: L
authors: Yang
authors: Department of Endocrinology, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors: Lei
authors: L
authors: Lei
authors: Department of Endocrinology, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors: Rongping
authors: R
authors: Chen
authors: Department of Endocrinology, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors: Hong
authors: H
authors: Chen
authors: Department of Endocrinology, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors: Hua
authors: H
authors: Zhang
mesh_terms: D062107:Advanced Oxidation Protein Products / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000098:blood supply*; D019255:NADPH Oxidases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D021122:Protein Subunits / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D062107:Advanced Oxidation Protein Products; D020011:Protective Agents; D021122:Protein Subunits; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D052216:Glucagon-Like Peptide 1; D019255:NADPH Oxidases; D053148:Caspase 3