Alcohol-induced oxidative stress in brain endothelial cells causes blood-brain barrier dysfunction

J. Haorah, B. Knipe, J. Leibhart, A. Ghorpade, Y. Persidsky

Research output: Contribution to journalArticlepeer-review

194 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1223-1232
Number of pages10
JournalJournal of Leukocyte Biology
Volume78
Issue number6
DOIs
StatePublished - Dec 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Keywords

  • Monocyte migration
  • Tight junctions

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