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Occludin oligomeric assembly at tight junctions of the blood-brain barrier is disrupted by peripheral inflammatory hyperalgesia.
J Neurochem. 2008 Sep; 106(6):2395-409.JN

Abstract

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 lambda-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 lambda-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 lambda-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.

Authors+Show Affiliations

Department of Medical Pharmacology, University of Arizona College of Medicine, Tucson, Arizona 85745, USA. gwenm@email.arizona.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18647175

Citation

McCaffrey, Gwen, et al. "Occludin Oligomeric Assembly at Tight Junctions of the Blood-brain Barrier Is Disrupted By Peripheral Inflammatory Hyperalgesia." Journal of Neurochemistry, vol. 106, no. 6, 2008, pp. 2395-409.
McCaffrey G, Seelbach MJ, Staatz WD, et al. Occludin oligomeric assembly at tight junctions of the blood-brain barrier is disrupted by peripheral inflammatory hyperalgesia. J Neurochem. 2008;106(6):2395-409.
McCaffrey, G., Seelbach, M. J., Staatz, W. D., Nametz, N., Quigley, C., Campos, C. R., Brooks, T. A., & Davis, T. P. (2008). Occludin oligomeric assembly at tight junctions of the blood-brain barrier is disrupted by peripheral inflammatory hyperalgesia. Journal of Neurochemistry, 106(6), 2395-409. https://doi.org/10.1111/j.1471-4159.2008.05582.x
McCaffrey G, et al. Occludin Oligomeric Assembly at Tight Junctions of the Blood-brain Barrier Is Disrupted By Peripheral Inflammatory Hyperalgesia. J Neurochem. 2008;106(6):2395-409. PubMed PMID: 18647175.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Occludin oligomeric assembly at tight junctions of the blood-brain barrier is disrupted by peripheral inflammatory hyperalgesia. AU - McCaffrey,Gwen, AU - Seelbach,Melissa J, AU - Staatz,William D, AU - Nametz,Nicole, AU - Quigley,Carolyn, AU - Campos,Chris R, AU - Brooks,Tracy A, AU - Davis,Thomas P, Y1 - 2008/07/21/ PY - 2008/7/24/pubmed PY - 2008/11/8/medline PY - 2008/7/24/entrez SP - 2395 EP - 409 JF - Journal of neurochemistry JO - J. Neurochem. VL - 106 IS - 6 N2 - 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 lambda-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 lambda-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 lambda-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. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/18647175/Occludin_oligomeric_assembly_at_tight_junctions_of_the_blood_brain_barrier_is_disrupted_by_peripheral_inflammatory_hyperalgesia_ L2 - https://doi.org/10.1111/j.1471-4159.2008.05582.x DB - PRIME DP - Unbound Medicine ER -