Inflammation and dephosphorylation of the tight junction protein occludin in an experimental model of multiple sclerosis

Abstract Multiple sclerosis (MS) is a disease of the CNS in which inflammation, demyelination and neurodegeneration contribute to its initiation and progression. A frequently employed model of MS is experimental autoimmune encephalomyelitis (EAE). Here, to gain new insights into the disease process,...

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Published in:	Neuroscience Vol. 147; no. 3; pp. 664 - 673
Main Authors:	Morgan, L, Shah, B, Rivers, L.E, Barden, L, Groom, A.J, Chung, R, Higazi, D, Desmond, H, Smith, T, Staddon, J.M
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 13-07-2007 Elsevier
Subjects:	Animals Biological and medical sciences blood–brain barrier Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges Cerebrospinal fluid. Meninges. Spinal cord Disease Models, Animal EAE edema Electrophoresis, Gel, Two-Dimensional - methods Encephalitis - etiology Encephalitis - metabolism Encephalitis - pathology Encephalomyelitis, Autoimmune, Experimental - complications Encephalomyelitis, Autoimmune, Experimental - metabolism Encephalomyelitis, Autoimmune, Experimental - pathology Endothelial Cells - cytology experimental autoimmune encephalomyelitis Female Fundamental and applied biological sciences. Psychology Immunoprecipitation - methods kinase Mass Spectrometry - methods Medical sciences Membrane Proteins - metabolism Nervous system (semeiology, syndromes) Neurology Occludin Phosphoric Monoester Hydrolases - pharmacology Phosphorylation - drug effects Rats Rats, Inbred Lew signaling Spinal Cord - pathology Tight Junctions - metabolism Vertebrates: nervous system and sense organs signaling BBB edema DTT signal-transducer and activator of transcription Laemmli sample buffer LRP phosphate-buffered saline lung-resistance protein blood–brain barrier experimental autoimmune encephalomyelitis days post-immunization immunoprecipitation Glut-1 LSB MBP sodium dodecyl sulfate–polyacrylamide gel electrophoresis PBS RSA dithiothreitol MALDI MS multiple sclerosis IP rat serum albumin EAE interferon-γ-induced GTPase myelin basic protein SDS-PAGE kinase STAT matrix-assisted laser desorption/ionization d.p.i IGTP glucose transporter-1 blood-brain barrier Nervous system diseases Encephalomyelitis Enzyme Transferases Central nervous system Cell junction Inflammation Dephosphorylation Blood brain barrier Protein Cerebral disorder Signal transduction Kinase Central nervous system disease Tight junction Models Spinal cord disease
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Summary:	Abstract Multiple sclerosis (MS) is a disease of the CNS in which inflammation, demyelination and neurodegeneration contribute to its initiation and progression. A frequently employed model of MS is experimental autoimmune encephalomyelitis (EAE). Here, to gain new insights into the disease process, an analysis of proteins in extracts of lumbar spinal cord from naïve and EAE rats was undertaken. The data mainly confirm that inflammation and blood–brain barrier (BBB) breakdown are the major hallmarks of disease in this model. Given their importance in the BBB, junctional proteins were further investigated. Occludin, a protein localizing to tight junctions in brain endothelial cells, showed strikingly increased migration in EAE when analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE). This increased migration was mimicked by in vitro phosphatase treatment, implying its dephosphorylation in EAE. Occludin dephosphorylation coincided with the onset of inflammation, slightly preceding visible signs of disease, and was just prior to apparent changes in BBB permeability. These findings suggest occludin is a target for signaling processes in EAE, perhaps regulating the response of the BBB to the inflammatory environment as seen in MS.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0306-4522 1873-7544
DOI:	10.1016/j.neuroscience.2007.04.051