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Cited by 121Barrier Structure and Function StudiesHIV Research and TreatmentCell Adhesion Molecules Research

The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.

Signaling Mechanisms of HIV-1 Tat-Induced Alterations of Claudin-5 Expression in Brain Endothelial Cells

András, Ibolya E, Pu, Hong, Tian, Jing, Deli, Mária A, Nath, Avindra, Hennig, Bernhard, Toborek, Michal·2005·Journal of Cerebral Blood Flow & Metabolism
DOI 10.1038/sj.jcbfm.9600115
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Abstract

Exposure of brain microvascular endothelial cells (BMEC) to human immunodeficiency virus-1 (HIV-1) Tat protein can decrease expression and change distribution of tight junction proteins, including claudin-5. Owing to the importance of claudin-5 in maintaining the blood–brain barrier (BBB) integrity, the present study focused on the regulatory mechanisms of Tat-induced alterations of claudin-5 mRNA and protein levels. Real-time reverse-transcription-polymerase chain reaction revealed that claudin-5 mRNA was markedly diminished in BMEC exposed to Tat. However, U0126 (an inhibitor of mitogen-activated protein kinase kinase1/2, MEK1/2) protected against this effect. In addition, inhibition of the vascular endothelial growth factor receptor type 2 (VEGFR-2) by SU1498, phosphatidylinositol-3 kinase (PI-3 K) by LY294002, nuclear factor-κB (NF-κB) by peptide SN50, and intracellular calcium by BAPTA/AM partially prevented Tat-mediated alterations in claudin-5 protein levels and immunoreactivity patterns. In contrast, inhibition of protein kinase C did not affect claudin-5 expression in Tat-treated cells. The present findings indicate that activation of VEGFR-2 and multiple redox-regulated signal transduction pathways are involved in Tat-induced alterations of claudin-5 expression. Because claudins constitute the major backbone of tight junctions, the present data are relevant to the disturbances of the BBB in the course of HIV-1 infection.

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Crossref · 10.1038/sj.jcbfm.9600115

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Research works printed but not linked: 5

  1. Barillari G, 1999, Blood, 94, 663
  2. Deli MA, 1997, Drug transport across the blood–brain barrier: in vivo and in vitro techniques, 23
  3. Rhodes RH, 1991, Pathol Annu, 26, 247
  4. Singer EJ, 1994, J Acquir Immune Defic Syndr, 7, 265
  5. Wu DT, 2000, J Neurovirol, 6, S82

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Metadata

Authors
András, I. E., Pu, H., Tian, J., Deli, M. A., Nath, A., Hennig, B., & Toborek, M.
Affiliations
  • Department of Surgery, University of Kentucky, Lexington, Kentucky, USA
  • University of Kentucky (US)
  • HUN-REN Szegedi Biológiai Kutatóközpont (HU)
  • Johns Hopkins University (US)
ORCID
Venue
Journal of Cerebral Blood Flow & Metabolism
Publisher
SAGE Publications
Published
2005-09
Volume
25
Issue
9
Pages
1159-1170
ISSN
  • 0271-678X (ISSN-L)
  • 1559-7016
DOI
10.1038/sj.jcbfm.9600115
OpenAlex
W1973010584
Cited by
121
References
59
Citations by year
2025: 3 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 3 · 2017: 6 · 2016: 8 · 2015: 4 · 2014: 7 · 2013: 7 · 2012: 9
FWCI
4.03
Type
journal article
Language
en
Open access
closed
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r21aa013843-03)
  • National Institute on Alcohol Abuse and Alcoholism (AA 013843)
  • National Institute of Mental Health (MH 63022, R01MH063022)
  • National Institute of Neurological Disorders and Stroke (R01NS039254, NS-39254)
  • National Institute of Environmental Health Sciences (P42ES007380)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
HIV-1 Tat protein, claudin-5, brain microvascular endothelial cells, blood-brain barrier, tight junction proteins, VEGFR2 signaling, PI3K signaling, NF-κB signaling, MEK1/2, redox signaling, intracellular calcium, protein kinase C, HIV-associated neurocognitive disorders
MeSH terms
Animals, Brain Chemistry, Calcium, Cells, Cultured, Chelating Agents, Membrane Proteins, Microscopy, Fluorescence, Genes, ras, RNA, Messenger, Blotting, Western, Signal Transduction, HIV-1, Down-Regulation, Gene Products, tat, NF-kappa B, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, Vascular Endothelial Growth Factor Receptor-2, Endothelial Cells, Rats, tat Gene Products, Human Immunodeficiency Virus, Claudin-5

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