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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0003593,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0023823,
umls-concept:C0023884,
umls-concept:C0026809,
umls-concept:C0181586,
umls-concept:C0205217,
umls-concept:C0348011,
umls-concept:C0596988,
umls-concept:C1314754,
umls-concept:C1412472,
umls-concept:C1512032,
umls-concept:C1705822,
umls-concept:C2243194
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pubmed:issue |
3
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pubmed:dateCreated |
1997-2-13
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pubmed:abstractText |
APOBEC-1 is a catalytic subunit of an apolipoprotein B (apoB) mRNA editing enzyme complex. In humans it is expressed only in the intestine, whereas in mice it is expressed in both the liver and intestine. APOBEC-1 exists as a spontaneous homodimer (Lau, P. P., Zhu, H.-J., Baldini, A., Charnsangavej, C., and Chan, L. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 8522-8526). We tested the editing activity and dimerization potential of three different mouse APOBEC-1 mutants using in vitro editing activity assay and immunoprecipitation in the presence of epitope-tagged APOBEC-1. One catalytically inactive mutant, mu1 (H61K/C93S/C96S), that retains its capacity to dimerize with wild-type APOBEC-1 was found to inhibit the editing activity of the latter and was thus a dominant negative mutant. Two other inactive mutants that dimerized poorly with APOBEC-1 failed to inhibit its activity. Intravenous injection of a mu1 adenovirus, Admu1, in C57BL/6J mice in vivo resulted in liver-specific expression of mu1 mRNA. On days 4 and 9 after virus injection, endogenous hepatic apoB mRNA editing was 23.3 +/- 5.0 and 36.8 +/- 5.7%, respectively, compared with 65.3 +/- 11 and 71.3 +/- 5.2%, respectively, for luciferase adenovirus-treated animals. Plasma apoB-100 accounted for 95 and 93% of total plasma apoB in Admu1 animals on days 4 and 9, respectively, compared with 78 and 72% in luciferase adenovirus animals. Plasma cholesterol on day 9 was 98 +/- 17 mg/dl in the mu1-treated animals, substantially higher than phosphate-buffered saline-treated (57 +/- 9 mg/dl) or luciferase-treated (71 +/- 12 mg/dl) controls. Fast protein liquid chromatography analysis of mouse plasma showed that the intermediate density/low density lipoprotein fractions in the animals treated with the dominant negative mutant adenovirus were much higher than those in controls. We conclude that active APOBEC-1 functions as a dimer and its activity is inhibited by a dominant negative mutant. Furthermore, apoB mRNA editing determines the availability of apoB-100, which in turn limits the amount of intermediate density/low density lipoprotein that can be formed in mice. Liver-specific inhibition of apoB mRNA editing is an important component of any strategy to enhance the value of mice as a model for human lipoprotein metabolism.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AICDA (activation-induced cytidine...,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins B,
http://linkedlifedata.com/resource/pubmed/chemical/Cytidine Deaminase,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/apolipoprotein B mRNA editing enzyme
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
272
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1456-60
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8999814-Adenoviridae,
pubmed-meshheading:8999814-Animals,
pubmed-meshheading:8999814-Apolipoproteins B,
pubmed-meshheading:8999814-Cytidine Deaminase,
pubmed-meshheading:8999814-Gene Transfer Techniques,
pubmed-meshheading:8999814-Humans,
pubmed-meshheading:8999814-Lipoproteins, LDL,
pubmed-meshheading:8999814-Liver,
pubmed-meshheading:8999814-Mice,
pubmed-meshheading:8999814-Mutagenesis, Site-Directed,
pubmed-meshheading:8999814-Mutation,
pubmed-meshheading:8999814-RNA, Messenger,
pubmed-meshheading:8999814-RNA Editing
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pubmed:year |
1997
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pubmed:articleTitle |
Tissue-specific inhibition of apolipoprotein B mRNA editing in the liver by adenovirus-mediated transfer of a dominant negative mutant APOBEC-1 leads to increased low density lipoprotein in mice.
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pubmed:affiliation |
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030-3498, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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