|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
39
|
|
pubmed:dateCreated |
2001-9-24
|
|
pubmed:abstractText |
The oxidative modification of low density lipoprotein (LDL) has been implicated in the early stage of atherosclerosis through multiple potential pathways, and 12/15-lipoxygenase is suggested to be involved in this oxidation process. We demonstrated previously that the 12/15-lipoxygenase overexpressed in mouse macrophage-like J774A.1 cells was required for the cell-mediated LDL oxidation. However, the mechanism of the oxidation of extracellular LDL by the intracellular 12/15-lipoxygenase has not yet been elucidated. In the present study, we found that not only the LDL receptor but also LDL receptor-related protein (LRP), both of which are cell surface native LDL-binding receptors, were down-regulated by the preincubation of the cells with cholesterol or LDL and up-regulated by lipoprotein-deficient serum. Moreover, 12/15-lipoxygenase-expressing cell-mediated LDL oxidation was decreased by the preincubation of the cells with LDL or cholesterol and increased by the preincubation with lipoprotein-deficient serum. Heparin-binding protein 44, an antagonist of the LDL receptor family, also suppressed the cell-mediated LDL oxidation in a dose-dependent manner. The cell-mediated LDL oxidation was dose-dependently blocked by an anti-LRP antibody but not by an anti-LDL receptor antibody. Furthermore, antisense oligodeoxyribonucleotides against LRP reduced the cell-mediated LDL oxidation under the conditions in which the expression of LRP was decreased. The results taken together indicate that LRP was involved essentially for the cell-mediated LDL oxidation by 12/15-lipoxygenase expressed in J774A.1 cells, suggesting an important pathophysiological role of this receptor-enzyme system as the initial trigger of the progression of atherosclerosis.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonate 12-Lipoxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonate 15-Lipoxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Heparin,
http://linkedlifedata.com/resource/pubmed/chemical/LDL-Receptor Related...,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Low Density Lipoprotein...,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Thiobarbituric Acid Reactive...
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Sep
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
28
|
|
pubmed:volume |
276
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
36454-9
|
|
pubmed:dateRevised |
2011-11-17
|
|
pubmed:meshHeading |
pubmed-meshheading:11479307-Animals,
pubmed-meshheading:11479307-Antibodies,
pubmed-meshheading:11479307-Arachidonate 12-Lipoxygenase,
pubmed-meshheading:11479307-Arachidonate 15-Lipoxygenase,
pubmed-meshheading:11479307-Carrier Proteins,
pubmed-meshheading:11479307-Cell Line,
pubmed-meshheading:11479307-Cholesterol,
pubmed-meshheading:11479307-DNA, Complementary,
pubmed-meshheading:11479307-Dose-Response Relationship, Drug,
pubmed-meshheading:11479307-Glycoproteins,
pubmed-meshheading:11479307-Heparin,
pubmed-meshheading:11479307-Humans,
pubmed-meshheading:11479307-LDL-Receptor Related Protein-Associated Protein,
pubmed-meshheading:11479307-Ligands,
pubmed-meshheading:11479307-Lipoproteins, LDL,
pubmed-meshheading:11479307-Low Density Lipoprotein Receptor-Related Protein-1,
pubmed-meshheading:11479307-Macrophages,
pubmed-meshheading:11479307-Mice,
pubmed-meshheading:11479307-Oligonucleotides, Antisense,
pubmed-meshheading:11479307-Oxygen,
pubmed-meshheading:11479307-Protein Binding,
pubmed-meshheading:11479307-Receptors, Immunologic,
pubmed-meshheading:11479307-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11479307-Swine,
pubmed-meshheading:11479307-Thiobarbituric Acid Reactive Substances,
pubmed-meshheading:11479307-Up-Regulation
|
|
pubmed:year |
2001
|
|
pubmed:articleTitle |
Low density lipoprotein receptor-related protein is required for macrophage-mediated oxidation of low density lipoprotein by 12/15-lipoxygenase.
|
|
pubmed:affiliation |
Department of Molecular Pharmacology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
