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Homocysteine attenuates blood brain barrier function by inducing oxidative stress and the junctional proteins
Author(s) -
Tyagi Neetu,
Kumar Munish,
Pushpakumar SB,
Lominadze David,
Moshal Karni S,
Sen Utpal,
Vacek Thomas Paul,
Tyagi Suresh C
Publication year - 2008
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.22.1_supplement.734.7
Subject(s) - oxidative stress , microbiology and biotechnology , blood–brain barrier , reactive oxygen species , mapk/erk pathway , chemistry , endothelial dysfunction , immunoprecipitation , oxidative phosphorylation , homocysteine , extracellular , kinase , biochemistry , biology , endocrinology , central nervous system , gene
Hyperhomocysteinmia (HHcy) is associated with neurological disorders and causes blood brain barrier (BBB) dysfunction. However, the mechanism of BBB dysfunction is unclear. We hypothesize that Hcy induces oxidative stress, activates inter‐endothelial junctional (TJ) proteins leading to BBB dysfunction. In this study mosue brain microvascular endothelial cells (MBEC) were treated with different doses of homocysteine (Hcy) for 18hrs. Reactive oxygen species (ROS) was detected using DCFH‐DA assay. The expression of junctional proteins and activation of mitogen activated protein kinases (MAPK) was analysised by Western‐blotting. The interaction of junctional proteins were investigated using co‐immunoprecipitation. Our results show that Hcy induces oxidative stress, which causes down regulation of the inter‐endothelial junctional proteins ((ZO‐1, caludin, occuldin). Furthermore, oxidative stress leads to disruption of the cadherin‐beta‐catenin complex and an activation of extracellular signal‐regulated kinase. In conclusion, Hcy‐induced oxidative stress leads to BBB dysfunction, in part by, activating TJ proteins.