Dept. of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, Odense M, Denmark.
Am J Physiol Renal Physiol. 2012 Apr 15;302(8):F1034-44. doi: 10.1152/ajprenal.00371.2011. Epub 2012 Jan 11.
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. Interestingly, however, water intake and diuresis were significantly higher at baseline in ACBP(-/-) mice compared with that of (+/+) mice. Subsequent to 20-h water deprivation, ACBP(-/-) mice exhibited increased diuresis, reduced urine osmolality, elevated hematocrit, and higher relative weight loss compared with (+/+) mice. There were no significant differences in plasma concentrations of renin, corticosterone, and aldosterone between mice of the two genotypes. After water deprivation, renal medullary interstitial fluid osmolality and concentrations of Na(+), K(+), and urea did not differ between genotypes and cAMP excretion was similar. Renal aquaporin-1 (AQP1), -2, and -4 protein abundances did not differ between water-deprived (+/+) and ACBP(-/-) mice; however, ACBP(-/-) mice displayed increased apical targeting of pS256-AQP2. AQP3 abundance was lower in 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.
酰基辅酶 A 结合蛋白 (ACBP) 是一种小的细胞内蛋白，可特异性结合并转运中长链酰基辅酶 A 酯。先前的研究表明，ACBP 广泛表达，但在产脂细胞类型以及许多上皮细胞中表达水平特别高。在这里，我们表明 ACBP 在人肾脏和鼠肾脏上皮中广泛表达，在近端卷曲小管中表达最高。为了阐明 ACBP 在肾上皮中的作用，使用靶向敲除 ACBP 基因的小鼠（ACBP(-/-)）来研究代谢笼中的水和 NaCl 平衡以及尿液浓缩能力。ACBP(-/-)和 (+/+) 小鼠的食物摄入和尿钠和钾排泄没有差异。然而，有趣的是，与 (+/+) 小鼠相比，ACBP(-/-) 小鼠的基础水摄入量和尿量明显更高。在 20 小时的水剥夺后，与 (+/+) 小鼠相比，ACBP(-/-) 小鼠的尿量增加，尿渗透压降低，红细胞压积升高，相对体重减轻。两种基因型小鼠的血浆肾素、皮质酮和醛固酮浓度没有差异。水剥夺后，两种基因型之间肾髓质间质液渗透压、Na(+)、K(+)和尿素浓度没有差异，cAMP 排泄相似。水剥夺后的 (+/+) 和 ACBP(-/-) 小鼠的肾水通道蛋白 1 (AQP1)、-2 和 -4 蛋白丰度没有差异；然而，ACBP(-/-) 小鼠的 pS256-AQP2 顶膜靶向增加。ACBP(-/-) 小鼠的 AQP3 丰度低于 (+/+) 对照动物。因此，我们得出结论，ACBP 对于完整的尿液浓缩能力是必要的。我们的数据表明，ACBP(-/-) 尿液浓缩能力缺陷可能是由于 AQP3 减少，导致集合管基底外侧膜的流出减少。
