期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 285, 期 14, 页码 10583-10590出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.078006
关键词
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资金
- Danish National Research Council
- Ingeborg
- Leo Danins Foundations
- Henry Hansen and Hustru's Fund
- NovoNordisk Foundation
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 S-35-amino acids. Upon sucrose gradient ultracentrifugation of the labeled medium, fractions were analyzed by apoB immunoprecipitation. S-35-Labeled apoB100 was recovered in similar to 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 similar to 90% in vivo by treating wild type mice with apoBantisense 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 apoB100containing lipoproteins. One biological effect may be to dampen excess storage of triglycerides in proximal tubule cells.
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