Breusegem Sophia Y, Takahashi Hideaki, Giral-Arnal Hector, Wang Xiaoxin, Jiang Tao, Verlander Jill W, Wilson Paul, Miyazaki-Anzai Shinobu, Sutherland Eileen, Caldas Yupanqui, Blaine Judith T, Segawa Hiroko, Miyamoto Ken-ichi, Barry Nicholas P, Levi Moshe
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA.
Am J Physiol Renal Physiol. 2009 Aug;297(2):F350-61. doi: 10.1152/ajprenal.90765.2008. Epub 2009 Jun 3.
Dietary potassium (K) deficiency is accompanied by phosphaturia and decreased renal brush border membrane (BBM) vesicle sodium (Na)-dependent phosphate (P(i)) transport activity. Our laboratory previously showed that K deficiency in rats leads to increased abundance in the proximal tubule BBM of the apical Na-P(i) cotransporter NaPi-IIa, but that the activity, diffusion, and clustering of NaPi-IIa could be modulated by the altered lipid composition of the K-deficient BBM (Zajicek HK, Wang H, Puttaparthi K, Halaihel N, Markovich D, Shayman J, Beliveau R, Wilson P, Rogers T, Levi M. Kidney Int 60: 694-704, 2001; Inoue M, Digman MA, Cheng M, Breusegem SY, Halaihel N, Sorribas V, Mantulin WW, Gratton E, Barry NP, Levi M. J Biol Chem 279: 49160-49171, 2004). Here we investigated the role of the renal Na-P(i) cotransporters NaPi-IIc and PiT-2 in K deficiency. Using Western blotting, immunofluorescence, and quantitative real-time PCR, we found that, in rats and in mice, K deficiency is associated with a dramatic decrease in the NaPi-IIc protein abundance in proximal tubular BBM and in NaPi-IIc mRNA. In addition, we documented the presence of a third Na-coupled P(i) transporter in the renal BBM, PiT-2, whose abundance is also decreased by dietary K deficiency in rats and in mice. Finally, electron microscopy showed subcellular redistribution of NaPi-IIc in K deficiency: in control rats, NaPi-IIc immunolabel was primarily in BBM microvilli, whereas, in K-deficient rats, NaPi-IIc BBM label was reduced, and immunolabel was prevalent in cytoplasmic vesicles. In summary, our results demonstrate that decreases in BBM abundance of the phosphate transporter NaPi-IIc and also PiT-2 might contribute to the phosphaturia of dietary K deficiency, and that the three renal BBM phosphate transporters characterized so far can be differentially regulated by dietary perturbations.
膳食钾(K)缺乏伴随着磷酸盐尿以及肾刷状缘膜(BBM)囊泡钠(Na)依赖性磷酸盐(P(i))转运活性降低。我们实验室先前表明,大鼠钾缺乏会导致近端小管BBM顶端钠-磷酸盐共转运体NaPi-IIa丰度增加,但NaPi-IIa的活性、扩散和聚集可被钾缺乏BBM改变的脂质组成所调节(Zajicek HK、Wang H、Puttaparthi K、Halaihel N、Markovich D、Shayman J、Beliveau R、Wilson P、Rogers T、Levi M。《肾脏国际》60:694 - 704,2001;Inoue M、Digman MA、Cheng M、Breusegem SY、Halaihel N、Sorribas V、Mantulin WW、Gratton E、Barry NP、Levi M。《生物化学杂志》279:49160 - 49171,2004)。在此,我们研究了肾钠-磷酸盐共转运体NaPi-IIc和PiT-2在钾缺乏中的作用。使用蛋白质免疫印迹法、免疫荧光法和定量实时PCR,我们发现,在大鼠和小鼠中,钾缺乏与近端小管BBM中NaPi-IIc蛋白丰度以及NaPi-IIc mRNA的显著降低相关。此外,我们记录了肾BBM中第三种钠偶联磷酸盐转运体PiT-2的存在,其丰度在大鼠和小鼠中也因膳食钾缺乏而降低。最后,电子显微镜显示钾缺乏时NaPi-IIc发生亚细胞重新分布:在对照大鼠中,NaPi-IIc免疫标记主要位于BBM微绒毛中,而在钾缺乏大鼠中,NaPi-IIc的BBM标记减少,免疫标记在细胞质囊泡中普遍存在。总之,我们的结果表明,磷酸盐转运体NaPi-IIc以及PiT-2的BBM丰度降低可能导致膳食钾缺乏引起的磷酸盐尿,并且迄今为止所表征的三种肾BBM磷酸盐转运体可受到膳食扰动的差异调节。