| http://purl.uniprot.org/citations/8995232 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/8995232 | http://www.w3.org/2000/01/rdf-schema#comment | "We have previously reported that plasma apolipoprotein (apo) E-containing high density lipoprotein particles have a potent anti-platelet action, apparently by occupying saturable binding sites in the cell surface. Here we show that purified apoE (10-50 microg/ml), complexed with phospholipid vesicles (dimyristoylphosphatidylcholine, DMPC), suppresses platelet aggregation induced by ADP, epinephrine, or collagen. This effect was not due to sequestration of cholesterol from platelet membranes; apoE x DMPC chemically modified with cyclohexanedione (cyclohexanedione-apoE x DMPC) did not inhibit aggregation but nevertheless removed similar amounts of cholesterol as untreated complexes, about 2% during the aggregation period. Rather we found that apoE influenced intracellular platelet signaling. Thus, apoE x DMPC markedly increased cGMP in ADP-stimulated platelets which correlated with the resulting inhibition of aggregation (r = 0.85; p < 0.01, n = 10), whereas cyclohexanedione-apoE x DMPC vesicles had no effect. One important cellular mechanism for up-regulation of cGMP is through stimulation of nitric oxide (NO) synthase, the NO generated by conversion of L-arginine to L-citrulline, binds to and activates guanylate cyclase. This signal transduction pathway was implicated by the finding that NO synthase inhibitors of distinct structural and functional types all reversed the anti-platelet action of apoE, whereas a selective inhibitor of soluble guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (100 nM), had a similar reversing action. Direct confirmation that apoE stimulates NO synthase was obtained by use of L-[3H]arginine; platelets pretreated with apoE x DMPC produced markedly more L-[3H]citrulline (0.71 +/-0.1 pmol/h/10(9) platelets) than controls (0.18 +/-0.03; p < 0.05). In addition, hemoglobin which avidly binds NO also suppressed the anti-aggregatory effect, indicating that apoE stimulated sufficient production of NO by platelets for extracellular release to occur. We conclude that apoE inhibits platelet aggregation through the L-arginine:NO signal transduction pathway."xsd:string |
| http://purl.uniprot.org/citations/8995232 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.272.1.89"xsd:string |
| http://purl.uniprot.org/citations/8995232 | http://purl.uniprot.org/core/author | "Graham A."xsd:string |
| http://purl.uniprot.org/citations/8995232 | http://purl.uniprot.org/core/author | "Owen J.S."xsd:string |
| http://purl.uniprot.org/citations/8995232 | http://purl.uniprot.org/core/author | "Riddell D.R."xsd:string |
| http://purl.uniprot.org/citations/8995232 | http://purl.uniprot.org/core/date | "1997"xsd:gYear |
| http://purl.uniprot.org/citations/8995232 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/8995232 | http://purl.uniprot.org/core/pages | "89-95"xsd:string |
| http://purl.uniprot.org/citations/8995232 | http://purl.uniprot.org/core/title | "Apolipoprotein E inhibits platelet aggregation through the L-arginine:nitric oxide pathway. Implications for vascular disease."xsd:string |
| http://purl.uniprot.org/citations/8995232 | http://purl.uniprot.org/core/volume | "272"xsd:string |
| http://purl.uniprot.org/citations/8995232 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/8995232 |
| http://purl.uniprot.org/citations/8995232 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/8995232 |
| http://purl.uniprot.org/uniprot/P02649#attribution-99C919EBEF0E1401590A64AEC723408A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/8995232 |
| http://purl.uniprot.org/uniprot/P02649#attribution-FB0A4A94F90B4BE94FCFA8FDB0504993 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/8995232 |