Source:http://linkedlifedata.com/resource/pubmed/id/11854443
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2002-2-20
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pubmed:abstractText |
Vesnarinone is an effective inotropic agent for treating congestive heart failure, but its clinical usage is restricted because of the severe side effect of agranulocytosis. In myeloid HL-60 cells, vesnarinone increased the intracellular content of a proapoptotic lipid mediator, ceramide, in a time- and dose-dependent manner. Vesnarinone-induced apoptosis was significantly enhanced by simultaneous treatment with a cell-permeable N-acetyl sphingosine (C2-ceramide). Treatment with neither vesnarinone, C2-ceramide, nor simultaneously with vesnarinone and C2-ceramide caused a marked increase of reactive oxygen intermediates (ROI) generation measured by the 2',7'-dichlorofluorescin method. However, oxidative damage judged by the production of lipid peroxidates and the nitroblue tetrazolium-reducing ability were enhanced more significantly by simultaneous treatment with vesnarinone and C2-ceramide than by vesnarinone alone. Moreover, vesnarinone inhibited catalase function both at the protein and activity level, and this inhibition was synergistically enhanced by C2-ceramide, and vesnarinone-induced oxidative damage and apoptosis were significantly suppressed by treatment of HL-60 cells with purified catalase. C2-ceramide enhanced vesnarinone-induced inhibition of the ROI-scavenging enzyme catalase at the levels of protein and activity in HL-60 cells; in contrast, however, vesnarinone did not induce ceramide generation, oxidative damage, or catalase depletion in HL-60/ves cells, where vesnarinone could not induce apoptosis. Taken together, the results suggest that vesnarinone induces myeloid cell apoptosis by increasing oxidative damage via ceramide-induced inhibition of catalase function.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Catalase,
http://linkedlifedata.com/resource/pubmed/chemical/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/N-acetylsphingosine,
http://linkedlifedata.com/resource/pubmed/chemical/Quinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine,
http://linkedlifedata.com/resource/pubmed/chemical/vesnarinone
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0026-895X
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pubmed:author |
pubmed-author:DaidoNaoharuN,
pubmed-author:DomaeNaochikaN,
pubmed-author:IwaiKazuyaK,
pubmed-author:KitanoToshiyukiT,
pubmed-author:KondoTadakazuT,
pubmed-author:OkazakiToshiroT,
pubmed-author:SuzukiYoshikoY,
pubmed-author:TashimaMasaroM,
pubmed-author:UchiyamaTakashiT,
pubmed-author:UmeharaHisanoriH,
pubmed-author:WatanabeMitsumasaM
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pubmed:issnType |
Print
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pubmed:volume |
61
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
620-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11854443-Antineoplastic Agents,
pubmed-meshheading:11854443-Apoptosis,
pubmed-meshheading:11854443-Catalase,
pubmed-meshheading:11854443-Cell Division,
pubmed-meshheading:11854443-Ceramides,
pubmed-meshheading:11854443-Drug Synergism,
pubmed-meshheading:11854443-Enzyme Inhibitors,
pubmed-meshheading:11854443-HL-60 Cells,
pubmed-meshheading:11854443-Humans,
pubmed-meshheading:11854443-Lipid Peroxidation,
pubmed-meshheading:11854443-Oxidative Stress,
pubmed-meshheading:11854443-Quinolines,
pubmed-meshheading:11854443-Sphingosine
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pubmed:year |
2002
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pubmed:articleTitle |
Vesnarinone causes oxidative damage by inhibiting catalase function through ceramide action in myeloid cell apoptosis.
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pubmed:affiliation |
Department of Hematology and Oncology, Clinical Sciences for Pathological Organs, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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