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
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