Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-8-6
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
6
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
319-24
pubmed:dateRevised
2007-11-14
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
pubmed:year
2004
pubmed:articleTitle
Ceramide triggers Weibel-Palade body exocytosis.
pubmed:affiliation
Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Md 21205, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't