Cited by 275Barrier Structure and Function StudiesAlcohol Consumption and Health EffectsNitric Oxide and Endothelin Effects

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

Haorah, J, Knipe, B, Leibhart, J, Ghorpade, A, Persidsky, Y·2005·Journal of Leukocyte Biology

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.

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Crossref · 10.1189/jlb.0605340

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69 of 69 references verified0 citation errors · 0 not checkable

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Authors
Haorah, J., Knipe, B., Leibhart, J., Ghorpade, A., & Persidsky, Y.
Affiliations
University of Nebraska Medical Center (US)
Corresponding author
Persidsky, Y
Venue
Journal of Leukocyte Biology
Published
2005-10-04
Volume
78
Issue
6
Pages
1223-1232
ISSN
  • 0741-5400 (ISSN-L)
  • 1938-3673
OpenAlex
W2114026423
Cited by
275
References
69
Citations by year
2026: 10 · 2025: 11 · 2024: 7 · 2023: 12 · 2022: 14 · 2021: 22 · 2020: 13 · 2019: 9 · 2018: 16 · 2017: 19 · 2016: 22 · 2015: 9 · 2014: 16 · 2013: 15 · 2012: 14
FWCI
5.84
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Leukocyte Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (R21 AA013846, R01 MH65151)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
alcohol-induced oxidative stress, blood-brain barrier dysfunction, brain microvascular endothelial cells, alcohol metabolism, reactive oxygen species, myosin light chain kinase, tight junctions, monocyte migration, acetaldehyde, neuroinflammation, alcohol abuse
MeSH terms
Acetaldehyde, Adult, Alcohol Dehydrogenase, Ethanol, Blood-Brain Barrier, Brain, Cell Movement, Cells, Cultured, Central Nervous System Depressants, Cerebral Arteries, Encephalitis, Energy Metabolism, Humans, Membrane Proteins, Reactive Oxygen Species, Oxidative Stress, Myosin Light Chains, Tight Junctions, Cytochrome P-450 CYP2E1, Alcohol-Induced Disorders, Nervous System, Endothelial Cells, Claudin-5, Occludin

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