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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
2010-11-5
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pubmed:abstractText |
Diarrhea-associated hemolytic uremic syndrome (D+HUS) is the most common cause of acute renal failure among children. Renal damage in D+HUS is caused by Shiga toxin (Stx), which is elaborated by Shigella dysenteriae and certain strains of Escherichia coli, in North America principally E coli O157:H7. Recent studies demonstrate that Stx also induces von Willebrand factor (VWF) secretion by human endothelial cells and causes thrombotic thrombocytopenic purpura, a disease with similarities to D+HUS, in Adamts13(-/-) mice. Stx occurs in 2 variants, Stx1 and Stx2, each of which is composed of 1 catalytically active A subunit that is responsible for cytotoxicity, and 5 identical B subunits that mediate binding to cell-surface globo-triaosylceramide. We now report that B subunits from Stx1 or Stx2 can stimulate the acute secretion of VWF in the absence of the cytotoxic A subunit. This rapid effect requires binding and clustering of globotriaosylceramide, and depends on plasma membrane cholesterol and caveolin-1 but not clathrin. Furthermore, similar to Stx2 holotoxin, the isolated Stx2B subunits induce thrombotic microangiopathy in Adamts13(-/-) mice. These results demonstrate the existence of a novel Stx B-induced lipid raft-dependent signaling pathway in endothelial cells that may be responsible for some of the biological effects attributed previously to the cytotoxic Stx A subunit.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ADAMTS13 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caveolin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Cholera Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Clathrin,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Shiga Toxins,
http://linkedlifedata.com/resource/pubmed/chemical/Trihexosylceramides,
http://linkedlifedata.com/resource/pubmed/chemical/globotriaosylceramide,
http://linkedlifedata.com/resource/pubmed/chemical/stxB toxin,
http://linkedlifedata.com/resource/pubmed/chemical/von Willebrand Factor
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1528-0020
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
4
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pubmed:volume |
116
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3653-9
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pubmed:dateRevised |
2011-11-4
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pubmed:meshHeading |
pubmed-meshheading:20644116-Animals,
pubmed-meshheading:20644116-Caveolin 1,
pubmed-meshheading:20644116-Cell Line,
pubmed-meshheading:20644116-Cholera Toxin,
pubmed-meshheading:20644116-Cholesterol,
pubmed-meshheading:20644116-Clathrin,
pubmed-meshheading:20644116-Endothelial Cells,
pubmed-meshheading:20644116-Gene Deletion,
pubmed-meshheading:20644116-Gene Knockdown Techniques,
pubmed-meshheading:20644116-Humans,
pubmed-meshheading:20644116-Metalloendopeptidases,
pubmed-meshheading:20644116-Mice,
pubmed-meshheading:20644116-Mice, Inbred C57BL,
pubmed-meshheading:20644116-Shiga Toxins,
pubmed-meshheading:20644116-Shigella dysenteriae,
pubmed-meshheading:20644116-Thrombotic Microangiopathies,
pubmed-meshheading:20644116-Trihexosylceramides,
pubmed-meshheading:20644116-von Willebrand Factor
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pubmed:year |
2010
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pubmed:articleTitle |
Shiga toxin B subunits induce VWF secretion by human endothelial cells and thrombotic microangiopathy in ADAMTS13-deficient mice.
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pubmed:affiliation |
Departments of Medicine, Biochemistry, and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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