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Mechanism of advanced glycation end products-induced hyperpermeability in endothelial cells

Guo Xiaohua, Huang Qiaobing, Chen Bo, Wang Shuyun, Hou Fanfan, Fu Ning

Department of pathophysiology, The Southern Medical University.Guangzhou 510515,Guangdong；China；Department of Immunology, The Southern Medical University.Guangzhou 510515,Guangdong

Abstract

The purpose of the present study was to investigate the effects of advanced glycation end products (AGEs) modified protein on the permeability of endothelium monolayers and morphological changes of actin cytoskeleton. The roles of receptor for AGEs (RAGE), oxidant stress and the activation of p38 MAPK pathway in this pathological procedure were elucidated. Human umbilical vein endothelial cells (HUVECs)-derived cell line (ECV304) were incubated with AGEs modified human serum albumin (AGE-HSA) in concentrations of 12.5, 25, 50, and 100 mg/ml respectively, for 2, 4, 8, 12 and 24 hours. As control, HSA of the same concentration was administered to cells. Then TRITC-albumin was added to evaluate Pa value that reflects the permeability of endothelial monolayer. Furthermore, to visualize the morphological changes of actin cytoskeleton, the treated cells were incubated with rhodamine-phalloidin to stain F-actin. The results showed that the trans-endothelial membrane flux of albumin was significantly increased in a concentration- and time-dependent manner upon the stimulation of AGE-HSA, accompanying with actin reorganization. The blockage of AGE and RAGE binding with anti-RAGE IgG and the pharmacological inhibition of NADPH oxidase or p38 MAP kinase greatly attenuated the AGE-induced hyperpermeability response, respectively. These results indicate that RAGE, NADPH oxidase and p38 MAPK are possibly involved in the mediation of AGEs-induced barrier dysfunction and actin cytoskeleton reorganization in endothelial cells.

Key words: advanced glycation end products (AGEs);endothelial cells monolayers permeability;actin cytoskeleton;RAGE;NADPH oxidase;p38 MAPK

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Citing This Article：

Guo Xiaohua, Huang Qiaobing, Chen Bo, Wang Shuyun, Hou Fanfan, Fu Ning. Mechanism of advanced glycation end products-induced hyperpermeability in endothelial cells. Acta Physiol Sin 2005; 57 (2): (in Chinese with English abstract).