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http://purl.uniprot.org/citations/8636110http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/8636110http://www.w3.org/2000/01/rdf-schema#comment"We have used the technique of adenovirus-mediated gene transfer to study the in vivo function of the very low density lipoprotein receptor (VLDLR) in low density lipoprotein receptor (LDLR) knockout mice. We generated a replication-defective adenovirus (AdmVLDLR) containing mouse VLDLR cDNA driven by a cytomegalovirus promoter. Transduction of cultured Hepa (mouse hepatoma) cells and LDLR-deficient CHO-ldlA7 cells in vitro by the virus led to high-level expression of immunoreactive VLDLR proteins with molecular sizes of 143 kDa and 161 kDa. Digestion of the cell extract with the enzymes neuraminidase, N-glycanase, and O-glycanase resulted in the stepwise lowering of the apparent size of the 161-kDa species toward the 143-kDa species. LDLR (-/-) mice fed a 0.2% cholesterol diet were treated with a single intravenous injection of 3 x 10(9) plaque-forming units of AdmVLDLR. Control LDLR (-/-) mice received either phosphate-buffered saline or AdLacZ, a similar adenovirus containing the LacZ cDNA instead of mVLDLR cDNA. Comparison of the plasma lipids in the 3 groups of mice indicates that in the AdmVLDL animals, total cholesterol is reduced by approximately 50% at days 4 and 9 and returned toward control values on day 21. In these animals, there was also a approximately 30% reduction in plasma apolipoprotein (apo) E accompanied by a 90% fall in apoB-100 on day 4 of treatment. By FPLC analysis, the major reduction in plasma cholesterol in the AdmVLDLR animals was accounted for by a marked reduction in the intermediate density lipoprotein/low density lipoprotein (IDL/LDL) fraction. Plasma VLDL, IDL/LDL, and HDL were isolated from the three groups of animals by ultracentrifugal flotation. In the AdmVLDLR animals, there was substantial loss (approximately 65%) of protein and cholesterol mainly in the IDL/LDL fraction on days 4 and 9. Nondenaturing gradient gel electrophoresis indicates a preferential loss of the IDL peak although the LDL peak was also reduced. When 125I-IDL was administered intravenously into animals on day 4, the AdmVLDLR animals cleared the 125I-IDL at a rate 5-10 times higher than the AdLacZ animals. We conclude that adenovirus-mediated transfer of the VLDLR gene induces high-level hepatic expression of the VLDLR and results in a reversal of the hypercholesterolemia in 0.2% cholesterol diet-fed LDLR (-/-, mice. The VLDLR overexpression appears to greatly enhance the ability of these animals to clear IDL, resulting in a marked lowering of the plasma IDL/LDL. Further testing of the use of the VLDLR gene as a therapeutic gene for the treatment of hypercholesterolemia is warranted."xsd:string
http://purl.uniprot.org/citations/8636110http://purl.org/dc/terms/identifier"doi:10.1074/jbc.271.12.6852"xsd:string
http://purl.uniprot.org/citations/8636110http://purl.uniprot.org/core/author"Kobayashi K."xsd:string
http://purl.uniprot.org/citations/8636110http://purl.uniprot.org/core/author"Chan L."xsd:string
http://purl.uniprot.org/citations/8636110http://purl.uniprot.org/core/author"Nakamuta M."xsd:string
http://purl.uniprot.org/citations/8636110http://purl.uniprot.org/core/author"Oka K."xsd:string
http://purl.uniprot.org/citations/8636110http://purl.uniprot.org/core/author"Teng B."xsd:string
http://purl.uniprot.org/citations/8636110http://purl.uniprot.org/core/author"Ishimura-Oka K."xsd:string
http://purl.uniprot.org/citations/8636110http://purl.uniprot.org/core/author"Forte T."xsd:string
http://purl.uniprot.org/citations/8636110http://purl.uniprot.org/core/author"Ishida B."xsd:string
http://purl.uniprot.org/citations/8636110http://purl.uniprot.org/core/date"1996"xsd:gYear
http://purl.uniprot.org/citations/8636110http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/8636110http://purl.uniprot.org/core/pages"6852-6860"xsd:string
http://purl.uniprot.org/citations/8636110http://purl.uniprot.org/core/title"Reversal of hypercholesterolemia in low density lipoprotein receptor knockout mice by adenovirus-mediated gene transfer of the very low density lipoprotein receptor."xsd:string
http://purl.uniprot.org/citations/8636110http://purl.uniprot.org/core/volume"271"xsd:string
http://purl.uniprot.org/citations/8636110http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/8636110
http://purl.uniprot.org/citations/8636110http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/8636110
http://purl.uniprot.org/uniprot/#_E9Q643-mappedCitation-8636110http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/8636110
http://purl.uniprot.org/uniprot/#_A0A1L1SRE8-mappedCitation-8636110http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/8636110
http://purl.uniprot.org/uniprot/#_F8WGI9-mappedCitation-8636110http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/8636110
http://purl.uniprot.org/uniprot/#_F6RKS4-mappedCitation-8636110http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/8636110
http://purl.uniprot.org/uniprot/#_F8WIN7-mappedCitation-8636110http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/8636110
http://purl.uniprot.org/uniprot/#_P35951-mappedCitation-8636110http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/8636110
http://purl.uniprot.org/uniprot/#_Q3U8R7-mappedCitation-8636110http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/8636110
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