Role of peroxisome proliferator-activated receptor-alpha in ileum tight junction alteration in mouse model of restraint stress.
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.
Mazzon
Emanuela
E
Istituto di Ricovero e Cura a Carattere Scientifico Centro Neurolesi Bonino-Pulejo, Messina, Italy.
Crisafulli
Concetta
C
Galuppo
Maria
M
Cuzzocrea
Salvatore
S
D000818:Animals; D017209:Apoptosis; D003106:Colon / Q000378:metabolism; D003672:Defecation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D007082:Ileum / Q000378:metabolism* / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D062793:Occludin; D047493:PPAR alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010539:Permeability; D010750:Phosphoproteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology; D019108:Tight Junctions / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D062826:Zonula Occludens-1 Protein; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
C494827:Bax protein, mouse; C495267:CTNNB1 protein, mouse; D053222:Fas Ligand Protein; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D047493:PPAR alpha; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; C569043:Tjp1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D051028:bcl-2-Associated X Protein; D051176:beta Catenin