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    STUDIA BIOLOGIA - Issue no. 1 / 2002  
         
  Article:   REGULATION OF THE EXPRESSION AND FUNCTIONS OF INTERENDOTHELIAL JUNCTIONAL PROTEINS IN CEREBRAL ENDOTHELIAL CELLS UNDER HYPOXIA AND OXIDATIVE STRESS.

Authors:  ERZSÉBET MÁRIA SZATMÁRI, ISTVÁN KRIZBAI.
 
       
         
  Abstract:  Cerebral microvessels are implicated in the pathogenesis of several disorders of the central nervous system (CNS), such as neoplasia, ischemia, hypoxia, epilepsy, multiple sclerosis, dementia. The mechanism of the blood-brain barrier (BBB) disturbance following cerebral ischemia is largely unknown. In the increased permeability of the barrier, endothelial cells (ECs) and astrocytes are directly affected. In our study, we used the immortalised rat brain endothelial cell line GP8 to investigate the direct effect of hypoxia and reoxygenation on BBB-associated functions. For production of hypoxia (5% CO2 and 95% N2) and reoxygenation (5% CO2, 70% N2 and 25% O2) we worked with a special chamber (Billups-Rothenburg). In addition, the oxidative stress was investigated by using 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), which continuously releases H2O2. We found significant changes in the expression of junctional proteins. While occludin and cadherin were downregulated in oxidative stress, no similar changes were seen in the case of ZO-2 and -catenin. Our data indicate that changes in junctional protein-protein interactions may be involved in the damage of the barrier function caused by oxidative stress. We investigated the possible role of mitogen-activated protein kinase (MAPK) signal transduction pathway in the disruption of intercellular junctions. Our results suggest an activation of extracellular signal-regulated kinase (ERK1/2) pathway in response to DMNQ in GP8 cells. Protease activities (matrix metalloproteinases - MMPs and tissue plasminogen activator - tPA) also increased after DMNQ treatment. These two classes of neutral proteases act in concert in different neurological diseases which are associated with increased capillary permeability.  
         
     
         
         
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