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Alcohol‐induced oxidative stress in brain endothelial cells causes blood‐brain barrier dysfunction
Author(s) -
Haorah J.,
Knipe B.,
Leibhart J.,
Ghorpade A.,
Persidsky Y.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0605340
Subject(s) - oxidative stress , blood–brain barrier , reactive oxygen species , biology , tight junction , microbiology and biotechnology , oxidative phosphorylation , myosin light chain kinase , biochemistry , endocrinology , central nervous system , phosphorylation
Brain microvascular endothelial cells (BMVEC) connected by tight junctions (TJ) form a tight monolayer at the blood‐brain barrier (BBB). We investigated the idea that BBB dysfunction seen in alcohol abuse is associated with oxidative stress stemming from ethanol (EtOH) metabolism in BMVEC. Exposure to EtOH induced catalytic activity/expression of EtOH‐metabolizing enzymes, which paralleled enhanced generation of reactive oxygen species (ROS). EtOH‐mediated oxidative stress led to activation of myosin light chain (MLC) kinase, phosphorylation of MLC and TJ proteins, decreased BBB integrity, and enhanced monocyte migration across BBB. Acetaldehyde or ROS donors mimicked changes induced by EtOH in BMVEC. Thus, oxidative stress resulting from alcohol metabolism in BMVEC can lead to BBB breakdown in alcohol abuse, serving as an aggravating factor in neuroinflammatory disorders.