rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2004-8-6
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pubmed:abstractText |
The sphingolipid ceramide mediates a variety of stress responses, including vascular inflammation and thrombosis. Activated endothelial cells release Weibel-Palade bodies, granules containing von Willebrand factor (vWF) and P-selectin, which induce leukocyte rolling and platelet adhesion and aggregation. We hypothesized that ceramide induces vascular inflammation and thrombosis in part by triggering Weibel-Palade body exocytosis. We added ceramide to human aortic endothelial cells and assayed Weibel-Palade body exocytosis by measuring the concentration of vWF released into the media. Exogenous ceramide induces vWF release from endothelial cells in a dose-dependent manner. Activators of endogenous ceramide production, neutral sphingomyelinase, or tumor necrosis factor-alpha also induce Weibel-Palade body exocytosis. We next studied NO effects on ceramide-induced Weibel-Palade body exocytosis because NO can inhibit vascular inflammation. The NO donor S-nitroso-N-acetylpenicillamine decreases ceramide-induced vWF release in a dose-dependent manner, whereas the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester increases ceramide-induced vWF release. In summary, our findings show that endogenous ceramide triggers Weibel-Palade body exocytosis, and that endogenous NO inhibits ceramide-induced exocytosis. These data suggest a novel mechanism by which ceramide induces vascular inflammation and thrombosis.
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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 |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1,2-bis(2-aminophenoxy)ethane...,
http://linkedlifedata.com/resource/pubmed/chemical/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/Desipramine,
http://linkedlifedata.com/resource/pubmed/chemical/Egtazic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester,
http://linkedlifedata.com/resource/pubmed/chemical/NOS3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type III,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingomyelin Phosphodiesterase,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/dihydroceramide
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1524-4571
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
6
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pubmed:volume |
95
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
319-24
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15217913-Aorta,
pubmed-meshheading:15217913-Cells, Cultured,
pubmed-meshheading:15217913-Ceramides,
pubmed-meshheading:15217913-Desipramine,
pubmed-meshheading:15217913-Dose-Response Relationship, Drug,
pubmed-meshheading:15217913-Egtazic Acid,
pubmed-meshheading:15217913-Endothelial Cells,
pubmed-meshheading:15217913-Endothelium, Vascular,
pubmed-meshheading:15217913-Enzyme Inhibitors,
pubmed-meshheading:15217913-Exocytosis,
pubmed-meshheading:15217913-Humans,
pubmed-meshheading:15217913-Interleukin-8,
pubmed-meshheading:15217913-NG-Nitroarginine Methyl Ester,
pubmed-meshheading:15217913-Nitric Oxide,
pubmed-meshheading:15217913-Nitric Oxide Synthase,
pubmed-meshheading:15217913-Nitric Oxide Synthase Type III,
pubmed-meshheading:15217913-Sphingomyelin Phosphodiesterase,
pubmed-meshheading:15217913-Tumor Necrosis Factor-alpha,
pubmed-meshheading:15217913-Weibel-Palade Bodies
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pubmed:year |
2004
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pubmed:articleTitle |
Ceramide triggers Weibel-Palade body exocytosis.
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pubmed:affiliation |
Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Md 21205, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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