The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Alcohol-induced oxidative stress in brain endothelial cells causes blood-brain barrier dysfunction
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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“The role of CYP2E1 in brain ethanol metabolism and its association with alcohol-mediated oxidative neuronal injury155–160 and aging-related AD and PD161 have also been suggested.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [158]
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Size-selective loosening of the blood-brain barrier in claudin-5–deficient mice
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Claudin-based tight junctions are crucial for the mammalian epidermal barrier
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Alcohol, oxidative stress and free radical damage
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Alcohol, oxidative stress, and free radical damage.
Wu, D., & Cederbaum, A. I. (2003) · Europe PMC (PubMed Central) · Cited by 651
Possible Involvement of Phosphorylation of Occludin in Tight Junction Formation
Sakakibara, A., Furuse, M., Saitou, M., Ando‐Akatsuka, Y., & Tsukita, S. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.6.1393 · Cited by 590
The Neuropathology of Alcohol-specific Brain Damage, or Does Alcohol Damage the Brain?
Harper, C. G. (1998) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199802000-00001 · Cited by 405
Development of the blood-brain barrier
Engelhardt, B. (2003) · Cell and Tissue Research · doi:10.1007/s00441-003-0751-z · Cited by 386
Blood-Brain Barrier Tight Junction Disruption in Human Immunodeficiency Virus-1 Encephalitis
Dallasta, L. M., Pisarov, L. A., Esplen, J. E., Werley, J., Moses, A. V., Nelson, J. A., & Achim, C. L. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65511-3 · Cited by 372
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Blood–brain Barrier: Structural Components and Function Under Physiologic and Pathologic Conditions
Persidsky, Y., Ramirez, S. H., Haorah, J., & Kanmogne, G. D. (2006) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-006-9025-3 · Cited by 922
Self-citationCrosstalk of tight junction components with signaling pathways
González-Mariscal, L., Tapia, R., & Chamorro, D. (2008) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2007.08.018 · Cited by 759
The blood–brain barrier in systemic infection and inflammation
Galea, I. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00757-x · Cited by 807
Luissint, A.-C., Artus, C., Glacial, F., Ganeshamoorthy, K., & Couraud, P.-O. (2012) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-9-23 · Cited by 654
Looking at the blood–brain barrier: Molecular anatomy and possible investigation approaches
Cardoso, F. L., Brites, D. M. T. O., & Brito, M. A. (2010) · Brain Research Reviews · doi:10.1016/j.brainresrev.2010.05.003 · Cited by 604
Metadata
- 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
- Publisher
- Oxford University Press (OUP)
- 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 (medical) › 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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