Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1
Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1
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近端肾小管损伤后血清 d-丝氨酸蓄积涉及中性氨基酸转运蛋白 Asc-1
DOI：
10.1038/s41598-019-53302-2
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发表时间：
2019
影响因子：
4.6
通讯作者：
Sasabe Jumpei
中科院分区：
文献类型：
--
作者：
Suzuki Masataka;Gonda Yusuke;Yamada Marina;Vandebroek Arno A.;Mita Masashi;Hamase Kenji;Yasui Masato;Sasabe Jumpei
手性分离揭示了肾脏疾病中血液和尿液中氨基酸水平的对映体特异性变化。血-/l-丝氨酸比率已被确定与基于肌酐的肾功能相关。然而，丝氨酸对映体的独特行为的机制还没有很好地理解。本研究采用顺铂诱导的肾小管损伤小鼠模型，探讨肾小管在丝氨酸对映体紊乱中的作用。顺铂治疗导致组织学上仅限于近端小管的肾小管损伤，并显示血清d-/l-丝氨酸比值显著增加，与血清肌酐和血尿氮（BUN）呈正相关。d-/l-丝氨酸比值的增加与肾脏中d-丝氨酸降解酶d-氨基酸氧化酶的活性无关。中性氨基酸转运蛋白的筛选结果显示，在肾小管和集合管中发现的Asc-1在顺铂处理后显著增加，这与血清丝氨酸的增加相关，体外研究表明，肾细胞系Asc-1被顺铂诱导，并介导d-丝氨酸（优选tol-丝氨酸）的内流。总的来说，这些结果表明，顺铂诱导的近端小管损伤伴随着小管和集合管中的Asc-1诱导，并导致血清丝氨酸积累。
Chiral separation has revealed enantio-specific changes in blood and urinary levels of amino acids in kidney diseases. Bloodd-/l-serine ratio has been identified to have a correlation with creatinine-based kidney function. However, the mechanism of distinctive behavior in serine enantiomers is not well understood. This study was performed to investigate the role of renal tubules in derangement of serine enantiomers using a mouse model of cisplatin-induced tubular injury. Cisplatin treatment resulted in tubular damage histologically restricted to the proximal tubules and showed a significant increase of serumd-/l-serine ratio with positive correlations to serum creatinine and blood urine nitrogen (BUN). The increasedd-/l-serine ratio did not associate with activity of ad-serine degrading enzyme,d-amino acid oxidase, in the kidney. Screening transcriptions of neutral amino acid transporters revealed that Asc-1, found in renal tubules and collecting ducts, was significantly increased after cisplatin-treatment, which correlates with serumd-serine increase.In vitrostudy using a kidney cell line showed that Asc-1 is induced by cisplatin and mediated influx ofd-serine preferably tol-serine. Collectively, these results suggest that cisplatin-induced damage of proximal tubules accompanies Asc-1 induction in tubules and collecting ducts and leads to serumd-serine accumulation.
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影响因子：
2.9
作者：
T. Watanabe;Y. Motomura;T. Suga
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DOI：
10.1006/bbrc.2002.6441
发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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