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Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1
Chiral separation has revealed enantio-specific changes in blood and urinary levels of amino acids in kidney diseases. Blood d-/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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853873/ https://www.ncbi.nlm.nih.gov/pubmed/31723194 http://dx.doi.org/10.1038/s41598-019-53302-2 |
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author | Suzuki, Masataka Gonda, Yusuke Yamada, Marina Vandebroek, Arno A. Mita, Masashi Hamase, Kenji Yasui, Masato Sasabe, Jumpei |
author_facet | Suzuki, Masataka Gonda, Yusuke Yamada, Marina Vandebroek, Arno A. Mita, Masashi Hamase, Kenji Yasui, Masato Sasabe, Jumpei |
author_sort | Suzuki, Masataka |
collection | PubMed |
description | Chiral separation has revealed enantio-specific changes in blood and urinary levels of amino acids in kidney diseases. Blood d-/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 serum d-/l-serine ratio with positive correlations to serum creatinine and blood urine nitrogen (BUN). The increased d-/l-serine ratio did not associate with activity of a d-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 serum d-serine increase. In vitro study using a kidney cell line showed that Asc-1 is induced by cisplatin and mediated influx of d-serine preferably to l-serine. Collectively, these results suggest that cisplatin-induced damage of proximal tubules accompanies Asc-1 induction in tubules and collecting ducts and leads to serum d-serine accumulation. |
format | Online Article Text |
id | pubmed-6853873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68538732019-11-19 Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1 Suzuki, Masataka Gonda, Yusuke Yamada, Marina Vandebroek, Arno A. Mita, Masashi Hamase, Kenji Yasui, Masato Sasabe, Jumpei Sci Rep Article Chiral separation has revealed enantio-specific changes in blood and urinary levels of amino acids in kidney diseases. Blood d-/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 serum d-/l-serine ratio with positive correlations to serum creatinine and blood urine nitrogen (BUN). The increased d-/l-serine ratio did not associate with activity of a d-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 serum d-serine increase. In vitro study using a kidney cell line showed that Asc-1 is induced by cisplatin and mediated influx of d-serine preferably to l-serine. Collectively, these results suggest that cisplatin-induced damage of proximal tubules accompanies Asc-1 induction in tubules and collecting ducts and leads to serum d-serine accumulation. Nature Publishing Group UK 2019-11-13 /pmc/articles/PMC6853873/ /pubmed/31723194 http://dx.doi.org/10.1038/s41598-019-53302-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Suzuki, Masataka Gonda, Yusuke Yamada, Marina Vandebroek, Arno A. Mita, Masashi Hamase, Kenji Yasui, Masato Sasabe, Jumpei Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1 |
title | Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1 |
title_full | Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1 |
title_fullStr | Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1 |
title_full_unstemmed | Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1 |
title_short | Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1 |
title_sort | serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter asc-1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853873/ https://www.ncbi.nlm.nih.gov/pubmed/31723194 http://dx.doi.org/10.1038/s41598-019-53302-2 |
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