Mice with targeted disruption of the acyl-CoA binding protein display attenuated urine concentrating ability and diminished renal aquaporin-3 abundance

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Resumé

The acyl-CoA binding protein (ACBP) is a small intracellular protein that specifically binds and transports medium to long chain acyl-CoA esters. Previous studies have shown that ACBP is ubiquitously expressed but found at particularly high levels in lipogenic cell types as well as in many epithelial cells. Here we show that ACBP is widely expressed in human and mouse kidney epithelium with the highest expression in the proximal convoluted tubules. To elucidate the role of ACBP in the renal epithelium, mice with targeted disruption of the ACBP gene (ACBP(-/-)) were used to study water and NaCl balance as well as urine concentrating ability in metabolic cages. Food intake and urinary excretion of Na(+) and K(+) did not differ between ACBP(-/-) and (+/+) mice. Water intake and diuresis were significantly higher at baseline in ACBP(-/-) mice compared to that of (+/+) mice. Subsequent to 20h water deprivation, ACBP(-/-) mice exhibited increased diuresis, reduced urine osmolality, elevated hematocrit and higher relative weight loss compared to (+/+) mice. There were no significant differences in plasma concentrations of renin, corticosterone and aldosterone between mice of the two genotypes. At baseline, renal medullary interstitial fluid osmolality was not different between genotypes. After water deprivation, renal medullary interstitial fluid osmolality rose significantly while osmolality and concentrations of Na(+), K(+) and urea did not differ between ACBP(-/-) and (+/+). Cyclic AMP excretion was similar. Renal aquaporin (AQP)-2 and -4 protein abundances did not differ between water-deprived ACBP (+/+) and (-/-) mice. AQP3 abundance was lower in water-deprived ACBP(-/-) mice than in (+/+) control animals. Thus, we conclude that ACBP is necessary for intact urine concentrating ability. Our data suggest that the deficiency in urine concentrating ability in the ACBP(-/-) may be caused by reduced AQP3 leading to impaired efflux over the basolateral membrane of the collecting duct.
OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology: Renal Physiology
Vol/bind302
Udgave nummer8
Sider (fra-til)F1034-F1044
ISSN1931-857X
DOI
StatusUdgivet - 2012

Fingeraftryk

Kidney Concentrating Ability
Aquaporin 3
Diazepam Binding Inhibitor
Kidney
Water Deprivation
Diuresis
Epithelium
Aquaporin 2

Citer dette

@article{072932f1330147749b40833db6abf56c,
title = "Mice with targeted disruption of the acyl-CoA binding protein display attenuated urine concentrating ability and diminished renal aquaporin-3 abundance",
abstract = "The acyl-CoA binding protein (ACBP) is a small intracellular protein that specifically binds and transports medium to long chain acyl-CoA esters. Previous studies have shown that ACBP is ubiquitously expressed but found at particularly high levels in lipogenic cell types as well as in many epithelial cells. Here we show that ACBP is widely expressed in human and mouse kidney epithelium with the highest expression in the proximal convoluted tubules. To elucidate the role of ACBP in the renal epithelium, mice with targeted disruption of the ACBP gene (ACBP(-/-)) were used to study water and NaCl balance as well as urine concentrating ability in metabolic cages. Food intake and urinary excretion of Na(+) and K(+) did not differ between ACBP(-/-) and (+/+) mice. Water intake and diuresis were significantly higher at baseline in ACBP(-/-) mice compared to that of (+/+) mice. Subsequent to 20h water deprivation, ACBP(-/-) mice exhibited increased diuresis, reduced urine osmolality, elevated hematocrit and higher relative weight loss compared to (+/+) mice. There were no significant differences in plasma concentrations of renin, corticosterone and aldosterone between mice of the two genotypes. At baseline, renal medullary interstitial fluid osmolality was not different between genotypes. After water deprivation, renal medullary interstitial fluid osmolality rose significantly while osmolality and concentrations of Na(+), K(+) and urea did not differ between ACBP(-/-) and (+/+). Cyclic AMP excretion was similar. Renal aquaporin (AQP)-2 and -4 protein abundances did not differ between water-deprived ACBP (+/+) and (-/-) mice. AQP3 abundance was lower in water-deprived ACBP(-/-) mice than in (+/+) control animals. Thus, we conclude that ACBP is necessary for intact urine concentrating ability. Our data suggest that the deficiency in urine concentrating ability in the ACBP(-/-) may be caused by reduced AQP3 leading to impaired efflux over the basolateral membrane of the collecting duct.",
author = "Stine Langaa and Maria Bloksgaard and Signe Bek and Ditte Neess and Rikke Norregaard and Hansen, {Pernille Bl} and Marcher, {Ann Britt} and Jorgen Frokiaer and Susanne Mandrup and Jensen, {Boye L}",
year = "2012",
doi = "10.1152/ajprenal.00371.2011",
language = "English",
volume = "302",
pages = "F1034--F1044",
journal = "American Journal of Physiology: Renal Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "8",

}

TY - JOUR

T1 - Mice with targeted disruption of the acyl-CoA binding protein display attenuated urine concentrating ability and diminished renal aquaporin-3 abundance

AU - Langaa, Stine

AU - Bloksgaard, Maria

AU - Bek, Signe

AU - Neess, Ditte

AU - Norregaard, Rikke

AU - Hansen, Pernille Bl

AU - Marcher, Ann Britt

AU - Frokiaer, Jorgen

AU - Mandrup, Susanne

AU - Jensen, Boye L

PY - 2012

Y1 - 2012

N2 - The acyl-CoA binding protein (ACBP) is a small intracellular protein that specifically binds and transports medium to long chain acyl-CoA esters. Previous studies have shown that ACBP is ubiquitously expressed but found at particularly high levels in lipogenic cell types as well as in many epithelial cells. Here we show that ACBP is widely expressed in human and mouse kidney epithelium with the highest expression in the proximal convoluted tubules. To elucidate the role of ACBP in the renal epithelium, mice with targeted disruption of the ACBP gene (ACBP(-/-)) were used to study water and NaCl balance as well as urine concentrating ability in metabolic cages. Food intake and urinary excretion of Na(+) and K(+) did not differ between ACBP(-/-) and (+/+) mice. Water intake and diuresis were significantly higher at baseline in ACBP(-/-) mice compared to that of (+/+) mice. Subsequent to 20h water deprivation, ACBP(-/-) mice exhibited increased diuresis, reduced urine osmolality, elevated hematocrit and higher relative weight loss compared to (+/+) mice. There were no significant differences in plasma concentrations of renin, corticosterone and aldosterone between mice of the two genotypes. At baseline, renal medullary interstitial fluid osmolality was not different between genotypes. After water deprivation, renal medullary interstitial fluid osmolality rose significantly while osmolality and concentrations of Na(+), K(+) and urea did not differ between ACBP(-/-) and (+/+). Cyclic AMP excretion was similar. Renal aquaporin (AQP)-2 and -4 protein abundances did not differ between water-deprived ACBP (+/+) and (-/-) mice. AQP3 abundance was lower in water-deprived ACBP(-/-) mice than in (+/+) control animals. Thus, we conclude that ACBP is necessary for intact urine concentrating ability. Our data suggest that the deficiency in urine concentrating ability in the ACBP(-/-) may be caused by reduced AQP3 leading to impaired efflux over the basolateral membrane of the collecting duct.

AB - The acyl-CoA binding protein (ACBP) is a small intracellular protein that specifically binds and transports medium to long chain acyl-CoA esters. Previous studies have shown that ACBP is ubiquitously expressed but found at particularly high levels in lipogenic cell types as well as in many epithelial cells. Here we show that ACBP is widely expressed in human and mouse kidney epithelium with the highest expression in the proximal convoluted tubules. To elucidate the role of ACBP in the renal epithelium, mice with targeted disruption of the ACBP gene (ACBP(-/-)) were used to study water and NaCl balance as well as urine concentrating ability in metabolic cages. Food intake and urinary excretion of Na(+) and K(+) did not differ between ACBP(-/-) and (+/+) mice. Water intake and diuresis were significantly higher at baseline in ACBP(-/-) mice compared to that of (+/+) mice. Subsequent to 20h water deprivation, ACBP(-/-) mice exhibited increased diuresis, reduced urine osmolality, elevated hematocrit and higher relative weight loss compared to (+/+) mice. There were no significant differences in plasma concentrations of renin, corticosterone and aldosterone between mice of the two genotypes. At baseline, renal medullary interstitial fluid osmolality was not different between genotypes. After water deprivation, renal medullary interstitial fluid osmolality rose significantly while osmolality and concentrations of Na(+), K(+) and urea did not differ between ACBP(-/-) and (+/+). Cyclic AMP excretion was similar. Renal aquaporin (AQP)-2 and -4 protein abundances did not differ between water-deprived ACBP (+/+) and (-/-) mice. AQP3 abundance was lower in water-deprived ACBP(-/-) mice than in (+/+) control animals. Thus, we conclude that ACBP is necessary for intact urine concentrating ability. Our data suggest that the deficiency in urine concentrating ability in the ACBP(-/-) may be caused by reduced AQP3 leading to impaired efflux over the basolateral membrane of the collecting duct.

U2 - 10.1152/ajprenal.00371.2011

DO - 10.1152/ajprenal.00371.2011

M3 - Journal article

C2 - 22237802

VL - 302

SP - F1034-F1044

JO - American Journal of Physiology: Renal Physiology

JF - American Journal of Physiology: Renal Physiology

SN - 1931-857X

IS - 8

ER -