Abstract
Restraint stress induces permeability changes in the small intestine, but little is known about the role of endogenous peroxisome proliferator-activated receptor-alpha (PPAR-alpha) ligand in the defects of the tight junction function. In the present study, we used PPAR-alpha knockout mice to understand the roles of endogenous PPAR-alpha on ileum altered permeability function in models of immobilization stress. The absence of a functional PPAR-alpha gene in PPAR-alpha knockout mice resulted in a significant augmentation of the degree of 1) TNF-alpha production in ileum tissues; 2) the alteration of zonula occludens-1, occludin, and beta-catenin (immunohistochemistry); and 3) apoptosis (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that endogenous PPAR-alpha ligands reduce the degree of tight junction permeability in the ileum tissues associated with immobilization stress, suggesting a possible role of endogenous PPAR-alpha ligands on ileum barrier dysfunction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Colon / metabolism
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Defecation
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Disease Models, Animal
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Endothelial Cells / metabolism
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Epithelial Cells / metabolism
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Fas Ligand Protein / metabolism
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Ileum / metabolism*
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Ileum / ultrastructure
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Intestinal Mucosa / metabolism*
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Intestinal Mucosa / ultrastructure
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Occludin
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PPAR alpha / deficiency
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PPAR alpha / genetics
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PPAR alpha / metabolism*
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Permeability
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Phosphoproteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Restraint, Physical
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Stress, Psychological / metabolism*
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Stress, Psychological / pathology
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Tight Junctions / metabolism*
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Tumor Necrosis Factor-alpha / metabolism
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Zonula Occludens-1 Protein
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bcl-2-Associated X Protein / metabolism
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beta Catenin / metabolism
Substances
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Bax protein, mouse
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CTNNB1 protein, mouse
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Fas Ligand Protein
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Membrane Proteins
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Occludin
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Ocln protein, mouse
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PPAR alpha
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Phosphoproteins
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Proto-Oncogene Proteins c-bcl-2
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Tjp1 protein, mouse
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Tumor Necrosis Factor-alpha
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Zonula Occludens-1 Protein
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bcl-2-Associated X Protein
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beta Catenin