Abstract
Lipopolysaccharide (LPS) is an endotoxin causing sepsis. Studies from our laboratory revealed impaired intestinal absorption of l-leucine and d-fructose in LPS-treated rabbits. The aim of this study was to examine intestinal d-galactose transport following intravenous administration of LPS in the rabbit and to identify the cellular mechanisms driving this process. Endotoxin treatment diminished the buildup of d-galactose in intestinal tissue, the mucosal to serosal transepithelial flux of the sugar and its uptake by brush border membrane vesicles (BBMVs). Intracellular signaling pathways associated with protein kinase C (PKC), protein kinase A (PKA), p38 mitogen-activated protein kinase (p38MAPK), Jun N-terminal kinase (JNK), MAPK/extracellular signal-regulated kinases 1 and 2 (MEK1/2) and proteasome were found to be involved in this reduction in sugar uptake. Na+/glucose cotransporter 1 (SGLT1) protein levels in BBMVs were lower for LPS-treated animals than control animals. These findings indicate that LPS inhibits the intestinal absorption of d-galactose via a complex cellular mechanism that could involve posttranscriptional regulation of the SGLT1 transporter.
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Acknowledgement
The SGLT1 rabbit polyclonal antibody and the cDNA clone were kindly provided by Dr. E. Wright (UCLA, Los Angeles, CA). This work was supported by grants from the Ministerio de Ciencia y Tecnología (AGL 2003–04497/GAN, PGE+FEDER) and the Departamento de Ciencia, Tecnología y Universidad del Gobierno de Aragón, Spain A-32. The group belongs to the Network for Cooperative Research on Membrane Transport Proteins, cofunded by the Ministerio de Educación y Ciencia, Spain, and the European Regional Development Fund (grant BFU2005-24983-E/BFI).
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Amador, P., García-Herrera, J., Marca, M.C. et al. Intestinal d-Galactose Transport in an Endotoxemia Model in the Rabbit. J Membrane Biol 215, 125–133 (2007). https://doi.org/10.1007/s00232-007-9012-5
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DOI: https://doi.org/10.1007/s00232-007-9012-5