Expression of apolipoprotein B in the kidney attenuates renal lipid accumulation

Marcin Krzystanek; Tanja Xenia Pedersen; Emil Daniel Bartels; Jacob Kjaehr; Ellen Marie Straarup; Lars Bo Nielsen

doi:10.1074/jbc.M109.078006

Expression of apolipoprotein B in the kidney attenuates renal lipid accumulation

Marcin Krzystanek, Tanja Xenia Pedersen, Emil Daniel Bartels, Jacob Kjaehr, Ellen Marie Straarup, Lars Bo Nielsen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

39 Citationer (Scopus)

Abstract

Udgivelsesdato: 2010-Apr

Originalsprog	Engelsk
Tidsskrift	Journal of Biological Chemistry
Vol/bind	285
Udgave nummer	14
Sider (fra-til)	10583-90
Antal sider	7
ISSN	0021-9258
DOI	https://doi.org/10.1074/jbc.M109.078006
Status	Udgivet - 2010

Bibliografisk note

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

Adgang til dokumentet

10.1074/jbc.M109.078006

Citationsformater

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title = "Expression of apolipoprotein B in the kidney attenuates renal lipid accumulation",

abstract = "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.",

author = "Marcin Krzystanek and Pedersen, {Tanja Xenia} and Bartels, {Emil Daniel} and Jacob Kjaehr and Straarup, {Ellen Marie} and Nielsen, {Lars Bo}",

note = "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",

year = "2010",

doi = "10.1074/jbc.M109.078006",

language = "English",

volume = "285",

pages = "10583--90",

journal = "Journal of Biological Chemistry",

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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

Y1 - 2010

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 (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.

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 (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.

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 -