RAGE ligands induce apoptotic cell death of pancreatic β-cells via oxidative stress
BW Lee, HY Chae, SJ Kwon… - International …, 2010 - spandidos-publications.com
BW Lee, HY Chae, SJ Kwon, SY Park, J Ihm, SH Ihm
International journal of molecular medicine, 2010•spandidos-publications.comActivation of the receptor for advanced glycation endproducts (RAGE) by its ligands leads to
cellular damage contributing to diabetic complications. It is not clearly known whether RAGE
ligands influence pancreatic β-cells. In this study, we investigated the expression of RAGE in
islet cells and the effect of RAGE ligands, S100b and HMG-1, on islet cells. RAGE was
expressed in INS-1 cells and isolated rat and human islets at mRNA and protein levels.
RAGE and its ligand, S100b, were detected on islet cells in 28-week-old diabetic OLETF …
cellular damage contributing to diabetic complications. It is not clearly known whether RAGE
ligands influence pancreatic β-cells. In this study, we investigated the expression of RAGE in
islet cells and the effect of RAGE ligands, S100b and HMG-1, on islet cells. RAGE was
expressed in INS-1 cells and isolated rat and human islets at mRNA and protein levels.
RAGE and its ligand, S100b, were detected on islet cells in 28-week-old diabetic OLETF …
Activation of the receptor for advanced glycation endproducts (RAGE) by its ligands leads to cellular damage contributing to diabetic complications. It is not clearly known whether RAGE ligands influence pancreatic β-cells. In this study, we investigated the expression of RAGE in islet cells and the effect of RAGE ligands, S100b and HMG-1, on islet cells. RAGE was expressed in INS-1 cells and isolated rat and human islets at mRNA and protein levels. RAGE and its ligand, S100b, were detected on islet cells in 28-week-old diabetic OLETF rats. Both S100b and HMG-1 induced apoptotic cell death of INS-1 and islet cells. This INS-1 cell apoptosis was accompanied by increased intracellular oxidative stress and inhibited by antioxidants or a NADPH oxidase inhibitor. Our results showing S100b/RAGE expression on islets of diabetic rat model and RAGE ligands-induced islet cell apoptosis via NADPH oxidase-mediated ROS generation suggest that RAGE ligands-RAGE interaction may contribute not only to the development of diabetic complications but also to the progressive β-cell loss in type 2 diabetes by inducing oxidative stress.
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