| Activation of PKC modulates blood-brain barrier endothelial cell permeability changes induced by hypoxia and posthypoxic reoxygenation. | |
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MedLine Citation:
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PMID: 15994856 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The blood-brain barrier (BBB) is a metabolic and physiological barrier important for maintaining brain homeostasis. The aim of this study was to determine the role of PKC activation in BBB paracellular permeability changes induced by hypoxia and posthypoxic reoxygenation using in vitro and in vivo BBB models. In rat brain microvessel endothelial cells (RMECs) exposed to hypoxia (1% O2-99% N2; 24 h), a significant increase in total PKC activity was observed, and this was reduced by posthypoxic reoxygenation (95% room air-5% CO2) for 2 h. The expression of PKC-betaII, PKC-gamma, PKC-eta, PKC-mu, and PKC-lambda also increased following hypoxia (1% O2-99% N2; 24 h), and these protein levels remained elevated following posthypoxic reoxygenation (95% room air-5% CO2; 2 h). Increases in the expression of PKC-epsilon and PKC-zeta were also observed following posthypoxic reoxygenation (95% room air-5% CO2; 2 h). Moreover, inhibition of PKC with chelerythrine chloride (10 microM) attenuated the hypoxia-induced increases in [14C]sucrose permeability. Similar to what was observed in RMECs, total PKC activity was also stimulated in cerebral microvessels isolated from rats exposed to hypoxia (6% O2-94% N2; 1 h) and posthypoxic reoxygenation (room air; 10 min). In contrast, hypoxia (6% O2-94% N2; 1 h) and posthypoxic reoxygenation (room air; 10 min) significantly increased the expression levels of only PKC-gamma and PKC-theta in the in vivo hypoxia model. These data demonstrate that hypoxia-induced BBB paracellular permeability changes occur via a PKC-dependent mechanism, possibly by differentially regulating the protein expression of the 11 PKC isozymes. |
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Authors:
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Melissa A Fleegal; Sharon Hom; Lindsay K Borg; Thomas P Davis |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S. Date: 2005-07-01 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 289 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-10-12 Completed Date: 2005-11-21 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H2012-9 Citation Subset: IM |
Affiliation:
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Dept. of Medical Pharmacology, College of Medicine, The Univ. of Arizona, 1501 N. Campbell Ave., Tucson, AZ 85724, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Algorithms Alkaloids Animals Benzophenanthridines Blood-Brain Barrier / drug effects, physiology* Blotting, Western Capillary Permeability / drug effects Cell Hypoxia / physiology* Cell Membrane Permeability / drug effects, physiology* Endothelial Cells / drug effects, physiology* Enzyme Activation / physiology Enzyme Inhibitors / pharmacology Female Isoenzymes / metabolism Male Oxygen / physiology* Phenanthridines / pharmacology Protein Kinase C / antagonists & inhibitors, metabolism, physiology* Rats Rats, Sprague-Dawley Sucrose / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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F32-NS-049894/NS/NINDS NIH HHS; R01-NS-39592/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Alkaloids; 0/Benzophenanthridines; 0/Enzyme Inhibitors; 0/Isoenzymes; 0/Phenanthridines; 34316-15-9/chelerythrine; 57-50-1/Sucrose; 7782-44-7/Oxygen; EC 2.7.11.13/Protein Kinase C |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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