Regulation of amino acid transporters in the rat remnant kidney
Regulation of amino acid transporters in the rat remnant kidney
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DOI：
10.1093/ndt/gfn752
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发表时间：
2009-07-01
影响因子：
6.1
通讯作者：
Soares-da-Silva, Patricio
中科院分区：
文献类型：
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作者：
Amaral, Joao S.;Pinho, Maria Joao;Soares-da-Silva, Patricio
背景。部分肾消融与代偿性肾生长、显著氮血症、钠部分排泄显著增加和溶质转运改变有关。本研究评估了残肾中适应性的发生，特别是肾氨基酸转运体和钠转运体的发生，以及它们在未切除肾后早期（24小时和1周）钠处理中的可能作用。8周龄Wistar大鼠进行右肾消融术（n = 10）。术后24小时（n = 5）和1周（n = 5）麻醉大鼠，取左肾。测定尿液和血浆中儿茶酚胺、钠、尿素和肌酐的水平。采用实时反转录PCR检测氨基酸和钠转运蛋白的基因表达。Western blot检测氨基酸和钠转运蛋白特异性抗体的表达。未切除（Unx） 24h的大鼠尿中L-DOPA、多巴胺和DOPAC的排泄量低于相应的Sham大鼠，同时Na+-K+- atp酶蛋白的表达增加（增加64%）。给药1周后，Unx大鼠出现残肾肥大、尿量增加和钠排泄量增加2倍。在整个研究过程中，Unx大鼠的NHE3 mRNA表达显著降低（降幅接近20%）。在未切除肾后24 h和1周，LAT1转录物和蛋白一致过表达。相比之下，24小时Unx大鼠的4F2hc和LAT2转录物丰度低于Sham大鼠（两种情况下均降低36%）。这些结果证明，单侧肾切除术后，氨基酸转运体LAT1、LAT2和4F2hc以及钠转运体Na+-K+- atp酶和NHE3的表达受到不同的调节。总之，本研究使我们能够描述非肾切除术后早期肾脏的适应性，这表明包括肾多巴胺能系统在内的多种调节钠稳态的机制相互作用，以及氨基酸转运蛋白和钠转运蛋白的丰度。
Background. Partial renal ablation is associated with compensatory renal growth, significant azotaemia, a significant increase in fractional excretion of sodium and changes in solute transport. The present study evaluated the occurrence of adaptations in the remnant kidney, especially in renal amino acid transporters and sodium transporters and their putative role in sodium handling in the early stages (24 h and 1 week) after uninephrectomy.Methods. Wistar rats aged 8 weeks old were submitted to renal ablation of the right kidney-Unx rats (n = 10). 24 hours (n = 5) and 1 week (n = 5) after surgery, rats were anesthetized and the left kidney was removed. Urinary and plasmatic levels of catecholamines, sodium, urea and creatinine were measured. Gene expression of the amino acid and sodium transporters was determined by Real-time reverse transcription PCR. Protein expression was evaluated by Western blot using specific antibodies for the amino acid and sodium transporters.Results. Uninephrectomized (Unx) rats for 24 h showed a lower urinary excretion of L-DOPA, dopamine and DOPAC than the corresponding Sham rats, accompanied by an increase in the expression of the Na+-K+-ATPase protein (64% increase). Unx rats for 1 week presented a hypertrophied remnant kidney, higher urine outflow and a similar to 2-fold increase in the fractional excretion of sodium. The NHE3 mRNA expression was significantly decreased in Unx rats throughout the study (similar to 20% decrease). LAT1 transcript and protein were consistently overexpressed at both 24 h and 1 week after uninephrectomy. In contrast, 4F2hc and LAT2 transcript abundance was lower in 24-h Unx rats than in Sham rats (a 36% decrease in both cases).Conclusions. These results provide evidence that the renal expression of the amino acid transporters LAT1, LAT2 and 4F2hc and the sodium transporters Na+-K+-ATPase and NHE3 is differently regulated following unilateral nephrectomy. In conclusion, this study allowed us to characterize the renal adaptations in the early stages after uninephrectomy, which showed a combined interaction of multiple mechanisms regulating sodium homeostasis including the renal dopaminergic system, and the abundance of amino acid transporters and sodium transporters.