Source:http://linkedlifedata.com/resource/pubmed/id/17822942
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2007-11-12
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pubmed:abstractText |
Sulfatides - sulfated derivatives of galactocerebroside - are endogenous ligands for P- and L-selectins and are able to induce intracellular signaling in neutrophils through a L-selectin dependent pathway. Sulfatides are implicated in a variety of physiological functions and have been found to suppress the synthesis of 5-lipoxygenase (5-LO) metabolites and impede 5-LO translocation to the nuclear envelope in adherent human polymorphonuclear leukocytes (PMNs) [Sud'ina, G. F., Brock, T. G., Pushkareva, M. A., Galkina, S. I., Turutin, D. V., Peters-Golden, M., et al. (2001). Sulphatides trigger polymorphonuclear granulocyte spreading on collagen-coated surfaces and inhibit subsequent activation of 5-lipoxygenase. The Biochemical Journal, 359, 621-629]. In this study we investigated the mechanism of the leukotriene (LT) synthesis inhibition by sulfatides. Sulfatides neither attenuated the ionophore-induced rise in [Ca(2+)](i) nor promoted PKA activation. We demonstrated that sulfatides directly inhibited 5-LO enzyme activity in a cell-free assay. BODIPY-labeled sulfatides were able to rapidly penetrate into the cells. Sulfatides induced rearrangement and redistribution of cytoskeletal components in adherent PMNs. The lipid incorporation as well as sulfatide-induced inhibition of LT synthesis were abolished by cytochalasin D, an inhibitor of actin polymerization and endocytosis. Importantly, sulfatides caused a prominent intracellular cholesterol redistribution, increasing its abundance at the uropod region. On the basis of these data, we suggest that increased cholesterol accumulation in cell compartments represents a novel mechanism by which sulfatides abrogate 5-LO translocation and activation.
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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/Arachidonate 5-Lipoxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Leukotrienes,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfoglycosphingolipids
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pubmed:status |
MEDLINE
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pubmed:issn |
1357-2725
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
110-24
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17822942-Arachidonate 5-Lipoxygenase,
pubmed-meshheading:17822942-Cell-Free System,
pubmed-meshheading:17822942-Cholesterol,
pubmed-meshheading:17822942-Enzyme Repression,
pubmed-meshheading:17822942-Fluorescent Antibody Technique,
pubmed-meshheading:17822942-Humans,
pubmed-meshheading:17822942-Intracellular Membranes,
pubmed-meshheading:17822942-Leukotrienes,
pubmed-meshheading:17822942-Lipid Mobilization,
pubmed-meshheading:17822942-Lipoxygenase Inhibitors,
pubmed-meshheading:17822942-Microtubules,
pubmed-meshheading:17822942-Neutrophils,
pubmed-meshheading:17822942-Sulfoglycosphingolipids
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pubmed:year |
2008
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pubmed:articleTitle |
Sulfatides inhibit leukotriene synthesis in human polymorphonuclear granulocytes by a mechanism involving lipid rearrangement in intracellular membranes.
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pubmed:affiliation |
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119992, Russia. zoryana@belozersky.msu.ru
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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