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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Size-selective loosening of the blood-brain barrier in claudin-5–deficient mice
Nitta, T., Hata, M., Gotoh, S., Seo, Y., Sasaki, H., Hashimoto, N., Furuse, M., & Tsukita, S. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200302070 · Cited by 1,917
Claudin-based tight junctions are crucial for the mammalian epidermal barrier
Furuse, M., Hata, M., Furuse, K., Yoshida, Y., Haratake, A., Sugitani, Y., Noda, T., Kubo, A., & Tsukita, S. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200110122 · Cited by 1,512
Alcohol, oxidative stress and free radical damage
Albano, E. (2006) · Proceedings of The Nutrition Society · doi:10.1079/pns2006496 · Cited by 1,223
Gendelman, H. E., Orenstein, J. M., Martin, M. A., Ferrua, C., Mitra, R., Phipps, T. J., Wahl, L. A., Lane, H. C., Fauci, A. S., & Burke, D. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.167.4.1428 · Cited by 781
Antonetti, D. A., Barber, A. J., Hollinger, L. A., Wolpert, E. B., & Gardner, T. W. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.33.23463 · Cited by 685
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
Oxidative Stress, Metabolism of Ethanol and Alcohol-Related Diseases
Zima, T., Fialová, L., Mestek, O., Kalousová, M., Crkovska, J., Malbohan, I. M., Štípek, S., Mikulikova, L., & Popov, P. (2001) · Journal of Biomedical Science · doi:10.1007/bf02255972 · Cited by 354
A model for monocyte migration through the blood-brain barrier during HIV-1 encephalitis
Persidsky, Y., Stins, M. F., Way, D., Witte, M., Weinand, M. E., Kim, K. S., Bock, P., Gendelman, H. E., & Fiala, M. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.7.3499 · Cited by 316
Self-citationFischer, S., Wobben, M., Marti, H. H., Renz, D., & Schaper, W. K. A. (2002) · Microvascular Research · doi:10.1006/mvre.2001.2367 · Cited by 316
Hirase, T., Kawashima, S., Wong, E. Y. M., Ueyama, T., Rikitake, Y., Tsukita, S., Yokoyama, M., & Staddon, J. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007136200 · Cited by 312
Phosphorylation of occludin correlates with occludin localization and function at the tight junction
Wong, V. (1997) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1997.273.6.c1859 · Cited by 295
Boven, L. A., Gomes, L., Héry, C., Gray, F., Verhoef, J., Portegies, P., Tardieu, M., & Nottet, H. S. L. M. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.7.4319 · Cited by 280
Antonetti, D. A., Wolpert, E. B., DeMaio, L., Harhaj, N. S., & Scaduto, R. C. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2001.00740.x · Cited by 270
Signaling in Leukocyte Transendothelial Migration
van Buul, J. D., & Hordijk, P. L. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000122854.76267.5c · Cited by 253
Interaction of SLP adaptors with the SH2 domain of Tec family kinases
Su, Y., Zhang, Y., Schweikert, J., Koretzky, G. A., Reth, M. G., & Wienands, J. (1999) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199911)29:11 · Cited by 242
Ingelman‐Sundberg, M., Johansson, I., Yin, H., Terelius, Y., Eliasson, E., Clot, P., & Albano, E. (1993) · Alcohol · doi:10.1016/0741-8329(93)90063-t · Cited by 227
H 2 O 2 -mediated permeability: role of MAPK and occludin
Kevil, C. G., Oshima, T., Alexander, B., Coe, L. L., & Alexander, J. S. (2000) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2000.279.1.c21 · Cited by 222
An automated colorimetric microassay for neuronotrophic factors
Manthorpe, M., Fagnani, R., Skaper, S. D., & Varon, S. S. (1986) · Developmental Brain Research · doi:10.1016/0165-3806(86)90208-7 · Cited by 219
Ethanol Increases Cytochrome P4502E1 and Induces Oxidative Stress in Astrocytes
Montoliu, C., Sancho‐Tello, M., Azorin, I., Burgal, M., Vallés, S., Renau‐Piqueras, J., & Guerri, C. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65062561.x · Cited by 218
Regional distribution of ethanol-inducible cytochrome P450 IIE1 in the rat central nervous system
Hansson, T., Tindberg, N., Ingelman-Sundberg, M., & Ko¨hler, C. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90154-v · Cited by 202
Tyrosine phosphorylation of occludin attenuates its interactions with ZO-1, ZO-2, and ZO-3
Kale, G., Naren, A. P., Sheth, P., & Rao, R. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)00167-0 · Cited by 196
Bovine Brain Microvessel Endothelial Cell Monolayers as a Model System for the Blood‐Brain Barriera
Audus, K. L., & Borchardt, R. T. (1987) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1987.tb45787.x · Cited by 178
Matheny, H. E., Deem, T. L., & Cook‐Mills, J. M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.12.6550 · Cited by 173
Haorah, J., Heilman, D., Knipe, B., Chrastil, J., Leibhart, J., Ghorpade, A., Miller, D. W., & Persidsky, Y. (2005) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000166944.79914.0a · Cited by 169
Self-citationLee, H.-S., Namkoong, K., Kim, D., Kim, K., Cheong, Y.-H., Kim, S., Lee, W.-B., & 김경용 (2004) · Microvascular Research · doi:10.1016/j.mvr.2004.07.005 · Cited by 162
Gendelman, H. E., Zheng, J., Coulter, C. L., Ghorpade, A., Che, M., Thylin, M. R., Rubocki, R. J., Persidsky, Y., Hahn, F. J. Y., Reinhard, J. F., et al. (1998) · The Journal of Infectious Diseases · doi:10.1086/515693 · Cited by 162
Self-citationMononuclear phagocyte immunity and the neuropathogenesis of HIV-1 infection
Persidsky, Y., & Gendelman, H. E. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0503205 · Cited by 161
Self-citationPotula, R., Poluektova, L. Y., Knipe, B., Chrastil, J., Heilman, D., Dou, H., Takikawa, O., Munn, D. H., Gendelman, H. E., & Persidsky, Y. (2005) · Blood · doi:10.1182/blood-2005-04-1403 · Cited by 159
Self-citationFrench, S. W., Wong, K., Jui, L., Albano, E., Hagbjörk, A.-L., & Ingelman‐Sundberg, M. (1993) · Experimental and Molecular Pathology · doi:10.1006/exmp.1993.1006 · Cited by 143
VCAM-1 signals during lymphocyte migration: role of reactive oxygen species
Cook‐Mills, J. M. (2002) · Molecular Immunology · doi:10.1016/s0161-5890(02)00206-7 · Cited by 132
Ethanol and Oxidative Mechanisms in the Brain
Sun, A. Y., & Sun, G. Y. (2001) · Journal of Biomedical Science · doi:10.1007/bf02255969 · Cited by 123
Effect of ethanol on cytochrome P450 in the rat brain.
Warner, M. N., & Gustafsson, J.-Α. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.3.1019 · Cited by 123
András, I. E., Pu, H., Tian, J., Deli, M. A., Nath, A., Hennig, B., & Toborek, M. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600115 · Cited by 121
Differential Regulation of Human Lung Epithelial and Endothelial Barrier Function by Thrombin
Kawkitinarong, K., Linz-McGillem, L. A., Birukov, K. G., & Garcia, J. G. N. (2004) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2003-0432oc · Cited by 104
Neuroimaging in Alcoholism: Ethanol and Brain Damage
Mann, K. F., Agartz, I., Harper, C. G., Shoaf, S. E., Rawlings, R. R., Momenan, R., Hommer, D. W., Pfefferbaum, A., Sullivan, E. V., Anton, R. F., et al. (2001) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2001.tb02383.x · Cited by 98
Neuroimaging in Alcoholism: Ethanol and Brain Damage
Mann, K. F., Agartz, I., Harper, C. G., Shoaf, S. E., Rawlings, R. R., Momenan, R., Hommer, D. W., Pfefferbaum, A., Sullivan, E. V., Anton, R. F., et al. (2001) · Alcoholism Clinical and Experimental Research · doi:10.1097/00000374-200105051-00019 · Cited by 96
Myosin Light Chain Phosphorylation in Neutrophil-Stimulated Coronary Microvascular Leakage
Yuan, S. Y., Wu, M. H., Ustinova, E. E., Guo, M., Tinsley, J. H., de Lanerolle, P., & Xu, W. (2002) · Circulation Research · doi:10.1161/01.res.0000020402.73609.f1 · Cited by 96
Induction of brain cytochrome P-450IIE1 by chronic ethanol treatmen
Anandatheerthavarada, H. K., Shankar, S. K., Bhamre, S., Boyd, M. R., Song, B.-J., & Ravindranath, V. (1993) · Brain Research · doi:10.1016/0006-8993(93)91721-4 · Cited by 90
THE GENESIS OF ALCOHOLIC BRAIN TISSUE INJURY
PRATT, O. E., ROOPRAI, H. K., Shaw, G. K., & Thomson, A. D. (1990) · Alcohol and Alcoholism · doi:10.1093/oxfordjournals.alcalc.a044995 · Cited by 88
Pu, H., Tian, J., Andras, I. E., Hayashi, K., Flora, G., Hennig, B., & Toborek, M. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600125 · Cited by 87
Farin, F. M., Pohlman, T. H., & Omiecinski, C. J. (1994) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1994.1001 · Cited by 85
Neuroimaging correlates of HIV-associated BBB compromise
Avison, M. J., Nath, A., Greene, R. A., Schmitt, F. A., Greenberg, R. N., & Berger, J. R. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.08.025 · Cited by 85
Ethanol Blocks Leukocyte Recruitment and Endothelial Cell Activation In Vivo and In Vitro
Saeed, R. W., Varma, S., Peng, T., Tracey, K. J., Sherry, B. A., & Metz, C. N. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.10.6376 · Cited by 83
Miller, D. W., Audus, K. L., & Borchardt, R. T. (1992) · Methods in Cell Science · doi:10.1007/bf01409014 · Cited by 80
Persson, J. O., Terelius, Y., & Ingelman‐Sundberg, M. (1990) · Xenobiotica · doi:10.3109/00498259009046904 · Cited by 80
Antioxidants and endothelium protection
Praticò, D. (2005) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2005.03.005 · Cited by 78
Velasquez, A., Bechara, R. I., Lewis, J. F., Malloy, J. L., McCaig, L., Brown, L. A. S., & Guidot, D. M. (2002) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2002.tb02663.x · Cited by 71
Distribution of alcohol dehydrogenase mRNA in the rat central nervous system.
Martínez, S. E., Vaglenova, J., Sabrià, J., Martı́nez, M. C., Farrés, J., & Parés, X. (2001) · European Journal of Biochemistry · doi:10.1046/j.0014-2956.2001.02416.x-i2 · Cited by 67
Kunsch, C., Luchoomun, J., Grey, J. Y., Olliff, L. K., Saint, L. B., Arrendale, R. F., Wasserman, M. A., Saxena, U., & Medford, R. M. (2004) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.059733 · Cited by 66
St. John's Wort Extract Induces CYP3A and CYP2E1 in the Swiss Webster Mouse
Bray, B. J. (2002) · Toxicological Sciences · doi:10.1093/toxsci/66.1.27 · Cited by 62
Establishment of a Recombinant Hepatic Cell Line Stably Expressing Alcohol Dehydrogenase
Clemens, D. L., Halgard, C. M., Miles, R. R., Sorrell, M. F., & Tuma, D. J. (1995) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1995.1400 · Cited by 61
Haorah, J., Heilman, D., Diekmann, C., Osna, N. A., Donohue, T. M., Ghorpade, A., & Persidsky, Y. (2004) · Cellular Immunology · doi:10.1016/j.cellimm.2004.07.005 · Cited by 56
Self-citationChronic ethanol consumption exacerbates microcirculatory damage in rat mesentery after reperfusion
Han, J.-Y., Miura, S., Akiba, Y., Higuchi, H., Kato, S., Suzuki, H., Yokoyama, H., & Ishii, H. (2001) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2001.280.5.g939 · Cited by 54
Sultatos, L. G. (1988) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22210-8 · Cited by 52
Proinflammatory synergism of ethanol and HIV-1 Tat protein in brain tissue
Flora, G., Pu, H., Lee, Y. W., Ravikumar, R., Nath, A., Hennig, B., & Toborek, M. J. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.06.007 · Cited by 49
Hoebel, B. G., Steyrer, E., & Graier, W. F. (1998) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.1998.tb02162.x · Cited by 47
Effects of Chronic Alcohol Abuse on Alveolar Epithelial Barrier Function and Glutathione Homeostasis
Burnham, E. L., Brown, L. A. S., Halls, L., & Moss, M. (2003) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000075821.34270.98 · Cited by 47
Effect of Chronic Alcohol Abuse on the CNS Morbidity of HIV Disease
Fein, G., Fletcher, D. J., & Sclafani, V. D. (1998) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1998.tb04000.x · Cited by 37
Kapucuoğlu, N., Çoban, T., Raunio, H., Pelkonen, O., Edwards, R. J., Boobis, A. R., & İşcan, M. (2003) · Cancer Letters · doi:10.1016/s0304-3835(03)00277-5 · Cited by 36
Davis, R. L., & Syapin, P. J. (2004) · Alcohol · doi:10.1016/j.alcohol.2004.01.006 · Cited by 34
Martínez, S. E., Vaglenova, J., Sabrià, J., Martı́nez, M. C., Farrés, J., & Parés, X. (2001) · European Journal of Biochemistry · doi:10.1046/j.0014-2956.2001.02416.x · Cited by 32
VERAPAMIL: METABOLISM IN CULTURES OF PRIMARY HUMAN CORONARY ARTERIAL ENDOTHELIAL CELLS
Borlak, J. T., Walles, M., Levsen, K., & Thum, T. (2003) · Drug Metabolism and Disposition · doi:10.1124/dmd.31.7.888 · Cited by 30
Belmadani, A. A., Neafsey, E. J., & Collins, M. (2003) · Journal of NeuroVirology · doi:10.1080/13550280390173409 · Cited by 26
Jiménez‐López, J. M., & Cederbaum, A. I. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.076737 · Cited by 9
The cell surface proteoglycan syndecan-1 mediates fibroblast growth factor-2 binding and activity
Filla, M. S., Dam, P., & Rapraeger, A. C. (1998) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(199803)174:3
Cited by
Sorted by citations
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review