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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
2005-11-1
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pubmed:abstractText |
Excessive apoptosis induced by enteric microbes leads to epithelial barrier defects. This mechanism has been implicated in the pathogenesis of inflammatory bowel diseases (IBD) and bacterial enteritis. The sodium-dependent glucose cotransporter (SGLT-1) is responsible for active glucose uptake in enterocytes. The aim was to investigate the effects of SGLT-1 glucose uptake on enterocyte apoptosis and barrier defects induced by bacterial lipopolysaccharide (LPS). SGLT-1-transfected Caco-2 cells were treated with LPS (50 mug/mL) in low (5 mM) or high (25 mM) glucose media. LPS in low glucose induced caspase-3 cleavage, DNA fragmentation, and increased paracellular permeability to dextran in epithelial cells. These phenomena were significantly attenuated in high glucose. LPS increased SGLT-1 activity in high, but not low glucose media. Addition of phloridzin, which competitively binds to SGLT-1, inhibited the cytoprotection mediated by high glucose. Western blot showed that LPS in high glucose increased the levels of anti-apoptotic Bcl-2 and Bcl-X(L,) and did not change proapoptotic Bax. Differential extraction of membranous vs. cytosolic cell components demonstrated that high glucose inhibits mitochondrial cytochrome c translocation to cytosol. Collectively, SGLT-1-mediated glucose uptake increases anti-apoptotic proteins, and protects enterocytes from LPS-induced apoptosis and barrier defects. The understanding of this novel glucose-mediated rescue mechanism may lead to therapeutic interventions for various enteric diseases.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phlorhizin,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/SLC5A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Glucose Transporter 1,
http://linkedlifedata.com/resource/pubmed/chemical/Voltage-Dependent Anion Channels,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/occludin
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1530-6860
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1822-35
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16260652-Apoptosis,
pubmed-meshheading:16260652-Binding, Competitive,
pubmed-meshheading:16260652-Biological Transport,
pubmed-meshheading:16260652-Blotting, Western,
pubmed-meshheading:16260652-Caco-2 Cells,
pubmed-meshheading:16260652-Caspase 3,
pubmed-meshheading:16260652-Caspase 8,
pubmed-meshheading:16260652-Caspase 9,
pubmed-meshheading:16260652-Caspases,
pubmed-meshheading:16260652-Cell Membrane,
pubmed-meshheading:16260652-Cytochromes c,
pubmed-meshheading:16260652-Cytosol,
pubmed-meshheading:16260652-DNA Fragmentation,
pubmed-meshheading:16260652-Enterocytes,
pubmed-meshheading:16260652-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:16260652-Epithelial Cells,
pubmed-meshheading:16260652-Glucose,
pubmed-meshheading:16260652-Humans,
pubmed-meshheading:16260652-Inflammatory Bowel Diseases,
pubmed-meshheading:16260652-Intestines,
pubmed-meshheading:16260652-Lipopolysaccharides,
pubmed-meshheading:16260652-Membrane Potentials,
pubmed-meshheading:16260652-Membrane Proteins,
pubmed-meshheading:16260652-Microscopy, Fluorescence,
pubmed-meshheading:16260652-Models, Biological,
pubmed-meshheading:16260652-Models, Statistical,
pubmed-meshheading:16260652-Permeability,
pubmed-meshheading:16260652-Phlorhizin,
pubmed-meshheading:16260652-Protein Binding,
pubmed-meshheading:16260652-Protein Transport,
pubmed-meshheading:16260652-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:16260652-Sodium-Glucose Transporter 1,
pubmed-meshheading:16260652-Time Factors,
pubmed-meshheading:16260652-Transfection,
pubmed-meshheading:16260652-Up-Regulation,
pubmed-meshheading:16260652-Voltage-Dependent Anion Channels,
pubmed-meshheading:16260652-bcl-X Protein
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pubmed:year |
2005
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pubmed:articleTitle |
SGLT-1-mediated glucose uptake protects intestinal epithelial cells against LPS-induced apoptosis and barrier defects: a novel cellular rescue mechanism?
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pubmed:affiliation |
Department of Biological Sciences, Mucosal Inflammation Research Group, University of Calgary, Calgary, AB, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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