Occludin oligomeric assembly at tight junctions of the blood-brain barrier is disrupted by peripheral inflammatory hyperalgesia
Open accessAbstract
Tight junctions (TJs) at the blood‐brain barrier (BBB) dynamically alter paracellular diffusion of blood‐borne substances from the peripheral circulation to the CNS in response to external stressors, such as pain, inflammation, and hypoxia. In this study, we investigated the effect of λ‐carrageenan‐induced peripheral inflammatory pain (i.e., hyperalgesia) on the oligomeric assembly of the key TJ transmembrane protein, occludin. Oligomerization of integral membrane proteins is a critical step in TJ complex assembly that enables the generation of tightly packed, large multiprotein complexes capable of physically obliterating the interendothelial space to inhibit paracellular diffusion. Intact microvessels isolated from rat brains were fractionated by detergent‐free density gradient centrifugation, and gradient fractions were analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis/ Western blot. Injection of λ‐carrageenan into the rat hind paw produced after 3 h a marked change in the relative amounts of oligomeric, dimeric, and monomeric occludin isoforms associated with different plasma membrane lipid raft domains and intracellular compartments in endothelial cells at the BBB. Our findings suggest that increased BBB permeability (i.e., leak) associated with λ‐carrageenan‐induced peripheral inflammatory pain is promoted by the disruption of disulfide‐bonded occludin oligomeric assemblies, which renders them incapable of forming an impermeant physical barrier to paracellular transport.
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Amyloid increases BBB permeability.
“Amyloid increases BBB permeability,124,125”
From Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging (2013) · cites this paper as [125]
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- Authors
- McCaffrey, G., Seelbach, M. J., Staatz, W. D., Nametz, N., Quigley, C., Campos, C. R., Brooks, T. A., & Davis, T. P.
- Affiliations
- University of Arizona (US)
- BIO5 Institute (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2008-09
- Volume
- 106
- Issue
- 6
- Pages
- 2395-2409
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC2656385
- OpenAlex
- W2000794581
- Cited by
- 71
- References
- 87
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 5 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 6 · 2012: 9
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01da011271-16)
- National Institute on Drug Abuse (R01-DA011271, R01-DA12684)
- National Cancer Institute (CA 09820-0251)
- National Institute of Neurological Disorders and Stroke (R01NS 39592, R01NS042652, R01NS039592, R01NS42652)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- occludin, tight junctions, blood-brain barrier, lambda-carrageenan, disulfide bonds, paracellular diffusion, blood-brain barrier permeability, lipid rafts, endothelial cells
- MeSH terms
- Animals, Biological Transport, Active, Blood-Brain Barrier, Carrageenan, Cell Compartmentation, Diffusion, Female, Hyperalgesia, Inflammation, Membrane Proteins, Microcirculation, Protein Binding, Rats, Sprague-Dawley, Tight Junctions, Protein Subunits, Membrane Microdomains, Endothelial Cells, Macromolecular Substances, Rats, 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 ›
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