Inhibitory effect of TNF-α on the intestinal absorption of galactose
Autor: | Mª. Jesus Rodríguez-Yoldi, J. de la Osada, P. Amador, María A. Navarro, M.T. Salvador, María Pilar Lostao, Sergio Acín, J. García-Herrera, M. C. Marca |
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Rok vydání: | 2007 |
Předmět: |
Lipopolysaccharides
Male Indoles Lipopolysaccharide Pyridines medicine.medical_treatment Pharmacology p38 Mitogen-Activated Protein Kinases Biochemistry Intestinal absorption Maleimides chemistry.chemical_compound Enzyme Inhibitors Intestinal Mucosa Protein Kinase C Anthracenes Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Microvilli Imidazoles Intestines medicine.anatomical_structure Cytokine Injections Intravenous Second messenger system Tumor necrosis factor alpha Rabbits Proteasome Inhibitors medicine.medical_specialty Enterocyte p38 mitogen-activated protein kinases Blotting Western Biology Sodium-Glucose Transporter 1 Sepsis Internal medicine medicine Animals RNA Messenger Protein Kinase Inhibitors Molecular Biology Protein kinase C Tumor Necrosis Factor-alpha Cell Membrane JNK Mitogen-Activated Protein Kinases Galactose Cell Biology Blotting Northern Cyclic AMP-Dependent Protein Kinases Endocrinology Intestinal Absorption chemistry Peptides |
Zdroj: | Journal of Cellular Biochemistry. 101:99-111 |
ISSN: | 1097-4644 0730-2312 |
DOI: | 10.1002/jcb.21168 |
Popis: | Sepsis is a systemic response to infection in which toxins, such as bacterial lipopolysaccharide (LPS), stimulate the production of inflammatory mediators like the cytokine tumor necrosis factor alpha (TNF-α). Previous studies from our laboratory have revealed that LPS inhibits the intestinal absorption of L-leucine and D-fructose in rabbit when it was intravenously administered, and that TNF-α seems to mediate this effect on amino acid absorption. To extend this work, the present study was designed to evaluate the possible effect of TNF-α on D-galactose intestinal absorption, identify the intracellular mechanisms involved and establish whether this cytokine mediates possible LPS effects. Our findings indicate that TNF-α decreases D-galactose absorption both in rabbit intestinal tissue preparations and brush-border membrane vesicles. Western blot analysis revealed reduced amounts of the Na+/glucose cotransporter (SGLT1) protein in the plasma membrane attributable to the cytokine. On the contrary, TNF-α increased SGLT1 mRNA levels. Specific inhibitors of the secondary messengers PKC, PKA, the MAP kinases p38 MAP, JNK, MEK1/2 as well as the proteasome, diminished the TNF-α-evoked inhibitory effect. LPS inhibition of the uptake of the sugar was blocked by a TNF-α antagonist. In conclusion, TNF-α inhibits D-galactose intestinal absorption by decreasing the number of SGLT1 molecules at the enterocyte plasma membrane through a mechanism in which several protein-like kinases are involved. J. Cell. Biochem. 101: 99–111, 2007. © 2006 Wiley-Liss, Inc. |
Databáze: | OpenAIRE |
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