| Characterization of recombinant human apoB-48-containing lipoproteins in rat hepatoma McA-RH7777 cells transfected with apoB-48 cDNA. Overexpression of apoB-48 decreases synthesis of endogenous apoB-100. | |
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MedLine Citation:
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PMID: 7749860 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We studied the effect of overexpression of apolipoprotein (apo) B-48 on the synthesis and secretion of endogenous apoB-100 in rat hepatoma McA-RH7777 cell lines stably transfected with human apoB-48 cDNA under the control of the cytomegalovirus promoter. Three cell lines that secrete 40 to 60 ng human apoB.mg cell protein-1.h-1 were used. The recombinant human apoB-48 exhibited physicochemical characteristics (buoyant density, 1.06 to 1.21 g/mL; beta-electrophoretic mobility and diameters, 16 to 20 nm) indistinguishable from those of endogenous rat apoB-48. Overexpression of the recombinant human apoB-48 resulted in a 50% decrease in the secretion of endogenous apoB-100 but did not affect the secretion of apoE or apoA-I. Several possible mechanisms for the decreased secretion of apoB-100 were evaluated. First, recruitment of lipids into lipoproteins was shown to be unaffected since no major changes in the physicochemical properties of apoB-100-containing lipoproteins were observed. Second, the intracellular degradation of apoB-100 was not altered as the intracellular retention half-time and secretion efficiency remained unaffected by apoB-48 overexpression. Third, the posttranslational regulatory mechanisms for apoB-100 remained normal, as demonstrated by a twofold increase in apoB-100 secretion after supplementation with oleic acid. Unexpectedly, a 35% to 50% decrease in the steady-state synthesis of endogenous apoB-100 was observed in apoB-48-transfected cells compared with control cells. These data suggested that decreased secretion of apoB-100 was secondary to decreased synthesis. The decreased apoB-100 synthesis was not due to decreased steady-state levels of rat apoB-100 mRNA. These results suggest that overexpression of recombinant human apoB-48 may interfere with posttranscriptional events, possibly at the translation-translocation level, and decrease translational yield of apoB-100. These posttranscriptional events prior to the complete synthesis of the apoB-100 polypeptide can be important in the control of apoB-100 secretion. |
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Authors:
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M M Hussain; Y Zhao; R K Kancha; B D Blackhart; Z Yao |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 15 ISSN: 1079-5642 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 1995 Apr |
Date Detail:
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Created Date: 1995-06-22 Completed Date: 1995-06-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 485-94 Citation Subset: IM |
Affiliation:
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Department of Pathology, Medical College of Pennsylvania, Philadelphia 19129, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Apolipoprotein B-100 Apolipoprotein B-48 Apolipoproteins B / biosynthesis, genetics*, metabolism Base Sequence Carcinoma, Hepatocellular / genetics, pathology DNA, Complementary / genetics Humans Lipoproteins / chemistry, genetics* Molecular Sequence Data Rats Recombinant Proteins / biosynthesis, genetics, metabolism Transfection Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Apolipoprotein B-100; 0/Apolipoprotein B-48; 0/Apolipoproteins B; 0/DNA, Complementary; 0/Lipoproteins; 0/Recombinant Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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