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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/G155    most recent 00139.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by García-Herrera, J. Articles by Rodríguez-Yoldi, M. J. PubMed PubMed Citation Articles by García-Herrera, J. Articles by Rodríguez-Yoldi, M. J.

INFLAMMATION/IMMUNITY/MEDIATORS

Protein kinases, TNF-, and proteasome contribute in the inhibition of fructose intestinal transport by sepsis in vivo

¹Physiology Unit, Department of Pharmacology and Physiology and ²Internal Medicine Unit, Department of Animal Pathology, Veterinary Faculty, University of Zaragoza, Zaragoza, Spain; ³Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 872, ⁴Université Pierre et Marie Curie-Paris 6, UMR S 872, Les Cordeliers; ⁵Université Paris Descartes-Paris 5, UMR S 872, Paris, France; and ⁶Biochemistry Unit, Department of Biochemistry and Molecular Biology, Veterinary Faculty, University of Zaragoza, Zaragoza, Spain

Submitted 28 March 2007 ; accepted in final form 4 October 2007

Lipopolysaccharide (LPS) endotoxin is a causative agent of sepsis. The aim of this study was to examine LPS effects on intestinal fructose absorption and to decipher mechanisms. Sepsis was induced by intravenous injection of LPS in rabbits. The ultrastructural study and DNA fragmentation patterns were identical in the intestine of LPS and sham animals. LPS treatment reduced fructose absorption altering both mucosal-to-serosal transepithelial fluxes and uptake into brush border membrane vesicles (BBMVs). Cytochalasin B was ineffective on fructose uptake, indicating that GLUT5, but not GLUT2, transport activity was targeted. GLUT5 protein levels in BBMvs were lower in LPS than in sham-injected rabbits. Thus lower fructose transport resulted from lower levels of GLUT5 protein. LPS treatment decreased GLUT5 levels by proteasome-dependent degradation. Specific inhibitors of PKC, PKA, and MAP kinases (p38MAPK, JNK, MEK1/2) protected fructose uptake from adverse LPS effect. Moreover, a TNF- antagonist blocked LPS action on fructose uptake. We conclude that intestinal fructose transport inhibition by LPS is associated with diminished GLUT5 numbers in the brush border membrane of enterocytes triggered by activation of several interrelated signaling cascades and proteasome degradation.

GLUT5; small intestine; LPS; intracellular signals; rabbit