TY - JOUR
T1 - Expression of apolipoprotein B in the kidney attenuates renal lipid accumulation
AU - Krzystanek, Marcin
AU - Pedersen, Tanja Xenia
AU - Bartels, Emil Daniel
AU - Kjaehr, Jacob
AU - Straarup, Ellen Marie
AU - Nielsen, Lars Bo
N1 - Keywords: Animals; Apolipoprotein B-100; Apolipoproteins B; Blotting, Western; Cholesterol; Humans; Kidney; Lipoproteins; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Oligonucleotides, Antisense; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Triglycerides
PY - 2010/4/2
Y1 - 2010/4/2
N2 - 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 35S-amino acids. Upon sucrose gradient ultracentrifugation of the labeled medium, fractions were analyzed by apoB immunoprecipitation. 35S-Labeled apoB100 was recovered in ∼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 ∼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 apoB100-containing lipoproteins. One biological effect may be to dampen excess storage of triglycerides in proximal tubule cells.
AB - 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 35S-amino acids. Upon sucrose gradient ultracentrifugation of the labeled medium, fractions were analyzed by apoB immunoprecipitation. 35S-Labeled apoB100 was recovered in ∼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 ∼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 apoB100-containing lipoproteins. One biological effect may be to dampen excess storage of triglycerides in proximal tubule cells.
U2 - 10.1074/jbc.M109.078006
DO - 10.1074/jbc.M109.078006
M3 - Journal article
C2 - 20103594
SN - 0021-9258
VL - 285
SP - 10583
EP - 10590
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 14
ER -