Effect of oxidative stress on the junctional proteins of cultured cerebral endothelial cells.
(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.
Krizbai
István A
IA
Institute of Biophysics, Biological Research Centre, Temesvári krt. 62, H-6726 Szeged, Hungary. krizbai@nucleus.szbk.u-szeged.hu
Bauer
Hannelore
H
Bresgen
Nicolaus
N
Eckl
Peter M
PM
Farkas
Attila
A
Szatmári
Erzsébet
E
Traweger
Andreas
A
Wejksza
Katarzyna
K
Bauer
Hans-Christian
HC
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D017097:Electric Impedance; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005947:Glucose / Q000493:pharmacokinetics; D020935:MAP Kinase Signaling System / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology; D062793:Occludin; D018384:Oxidative Stress / Q000502:physiology*; D019108:Tight Junctions / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009285:Naphthoquinones; D062793:Occludin; C568986:Ocln protein, mouse; D015534:Trans-Activators; D051176:beta Catenin; C502406:fat1 protein, mouse; C063002:2,3-dimethoxy-1,4-naphthoquinone; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose