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Effect of Oxidative Stress on the Junctional Proteins of Cultured Cerebral Endothelial Cells
Authors:Email author" target="_blank">István?A?KrizbaiEmail author  Hannelore?Bauer  Nicolaus?Bresgen  Peter?M?Eckl  Attila?Farkas  Erzsébet?Szatmári  Andreas?Traweger  Katarzyna?Wejksza  Hans-Christian?Bauer
Institution:(1) Biological Research Centre, Institute of Biophysics, Temesvári krt. 62, H-6726 Szeged, Hungary;(2) ABT, Department of Organismic Biology, University of Salzburg, Hellbrunner str. 34, A-5020 Salzburg, Austria;(3) Department of Cell Biology, University of Salzburg, Hellbrunner str. 34, A-5020 Salzburg, Austria;(4) Institute of Biophysics, Biological Research Centre, Temesvári krt. 62, H-6701, Szeged, POB 521, Hungary
Abstract:Summary 1. There is increasing evidence that the cerebral endothelium and the blood–brain barrier (BBB) plays an important role in the oxidative stress-induced brain damage. The aim of the present study was to investigate the role of interendothelial junctional proteins in the BBB permeability increase induced by oxidative stress.2. For the experiments, we have used cultured cerebral endothelial cells exposed to hypoxia/reoxygenation or treated with the redox cycling quinone 2,3-Dimethoxy-1,4-naphthoquinone (DMNQ) in the presence or absence of glucose. The expression of junctional proteins and activation of mitogen activated protein kinases (MAPK) was followed by Western-blotting, the interaction of junctional proteins was investigated using coimmunoprecipitation.3. Oxidative stress induces a downregulation of the tight junction protein occludin expression which is more pronounced in the absence of glucose. Furthermore, oxidative stress leads to disruption of the cadherin-beta-catenin complex and an activation of extracellular signal-regulated kinase (ERK1/2), which is more intense in the absence of glucose.4. We have shown that one of the causes of the BBB breakdown is probably the structural alteration of the junctional complex caused by oxidative stress, a process in which ERK1/2 may play an important role.This revised article was published online in May 2005 with a February 2005 cover date.
Keywords:cerebral endothelial cells  oxidative stress  occludin  tight junction  MAPK
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