globotriaosylceramide and Thrombotic-Microangiopathies

globotriaosylceramide has been researched along with Thrombotic-Microangiopathies* in 1 studies

Other Studies

1 other study(ies) available for globotriaosylceramide and Thrombotic-Microangiopathies

ArticleYear
Shiga toxin B subunits induce VWF secretion by human endothelial cells and thrombotic microangiopathy in ADAMTS13-deficient mice.
    Blood, 2010, Nov-04, Volume: 116, Issue:18

    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.

    Topics: ADAMTS13 Protein; Animals; Caveolin 1; Cell Line; Cholera Toxin; Cholesterol; Clathrin; Endothelial Cells; Gene Deletion; Gene Knockdown Techniques; Humans; Metalloendopeptidases; Mice; Mice, Inbred C57BL; Shiga Toxins; Shigella dysenteriae; Thrombotic Microangiopathies; Trihexosylceramides; von Willebrand Factor

2010