| Expression of apolipoprotein B in the kidney attenuates renal lipid accumulation. | |
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MedLine Citation:
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PMID: 20103594 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The ability to produce apolipoprotein (apo) B-containing lipoproteins enables hepatocytes, enterocytes, and cardiomyocytes to export triglycerides. In this study, we examined secretion of apoB-containing lipoproteins from mouse kidney and its putative impact on triglyceride accumulation in the tubular epithelium. Mouse kidney expressed both the apoB and microsomal triglyceride transfer protein genes, which permit lipoprotein formation. To examine de novo lipoprotein secretion, kidneys from human apoB-transgenic mice were minced and placed in medium with (35)S-amino acids. Upon sucrose gradient ultracentrifugation of the labeled medium, fractions were analyzed by apoB immunoprecipitation. (35)S-Labeled apoB100 was recovered in approximately 1.03-1.04 g/ml lipoproteins (i.e. similar to the density of plasma low density lipoproteins). Immunohistochemistry of kidney sections suggested that apoB mainly is produced by tubular epithelial cells. ApoB expression in the kidney cortex was reduced approximately 90% in vivo by treating wild type mice with apoB-antisense locked nucleic acid oligonucleotide. Inhibition of apoB expression increased fasting-induced triglyceride accumulation in the kidney cortex by 20-25% (p = 0.008). Cholesterol stores were unaffected. Treatment with control oligonucleotides with 1 or 4 mismatching base pairs affected neither the triglyceride nor the cholesterol content of the kidney cortex. The results suggest that mammalian kidney secretes apoB100-containing lipoproteins. One biological effect may be to dampen excess storage of triglycerides in proximal tubule cells. |
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Authors:
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Marcin Krzystanek; Tanja Xenia Pedersen; Emil Daniel Bartels; Jacob Kjaehr; Ellen Marie Straarup; Lars Bo Nielsen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-26 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-29 Completed Date: 2010-05-14 Revised Date: 2011-07-27 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 10583-90 Citation Subset: IM |
Affiliation:
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Department of Clinical Biochemistry, Rigshospitalet, DK-2100 Copenhagen. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apolipoprotein B-100 / genetics, metabolism Apolipoproteins B / physiology* Blotting, Western Cholesterol / metabolism* Humans Kidney / cytology, metabolism* Lipoproteins / genetics, metabolism Membrane Transport Proteins / genetics, metabolism Mice Mice, Inbred C57BL Mice, Transgenic Oligonucleotides, Antisense / pharmacology RNA, Messenger / genetics, metabolism Reverse Transcriptase Polymerase Chain Reaction Triglycerides / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Apolipoprotein B-100; 0/Apolipoproteins B; 0/Laptm4a protein, mouse; 0/Lipoproteins; 0/Membrane Transport Proteins; 0/Oligonucleotides, Antisense; 0/RNA, Messenger; 0/Triglycerides; 57-88-5/Cholesterol |
| Comments/Corrections | |
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