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Glutamate‐induced alterations of tight junction protein expression and distribution in brain endothelial cells
Author(s) -
Andras Ibolya E,
Hayashi Kentaro,
Hennig Bernhard,
Toborek Michal
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a378
Subject(s) - occludin , tight junction , glutamate receptor , ampa receptor , microbiology and biotechnology , nmda receptor , blood–brain barrier , chemistry , excitotoxicity , cell junction , biology , neuroscience , receptor , central nervous system , biochemistry , cell
The extracellular levels of the major excitatory neurotransmitter, glutamate, can increase dramatically in cerebral ischemia and stroke. This may lead to opening of the blood‐brain barrier (BBB) and induce further brain damage. Since endothelial tight junctions are critical elements of the BBB integrity, the aim of our study was to investigate the mechanisms of glutamate‐induced alterations of tight junction protein expression in cultured brain endothelial cells. Transient exposure to glutamate resulted in a marked downregulation and redistribution of occludin, JAM‐1 and ZO‐2, while expression and immunoreactivity of claudin‐1, claudin‐5 and ZO‐1 were not affected. Glutamate‐induced changes in occludin immunoreactivity were partially blocked by the NMDA‐receptor antagonist MK‐801 and by the AMPA/KA‐receptor antagonist DNQX. Immunoprecipitation experiments revealed that treatment with glutamate can also alter occludin phosphorylation as well as association of occludin with other tight junction proteins and with the actin cytoskeleton. Overall, our findings contribute to the better understanding of the mechanisms of glutamate‐induced BBB disruption in cerebral ischemia and stroke. Supported by MH63022, MH072567, NS39254, and AA013843.