Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1

Masataka Suzuki, Yusuke Gonda, Marina Yamada, Arno A. Vandebroek, Masashi Mita, Kenji Hamase, Masato Yasui, Jumpei Sasabe

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number16705
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

Fingerprint

Neutral Amino Acid Transport Systems
Serine
Kidney
Serum
Cisplatin
Creatinine
Amino Acids
Kidney Diseases
Oxidoreductases
Nitrogen

All Science Journal Classification (ASJC) codes

  • General

Cite this

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.

In: Scientific reports, Vol. 9, No. 1, 16705, 01.12.2019.

Research output: Contribution to journalArticle

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. In: Scientific reports. 2019 ; Vol. 9, No. 1.
@article{e1fa3e7eada84e70ae58b3931c0900c2,
title = "Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1",
abstract = "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.",
author = "Masataka Suzuki and Yusuke Gonda and Marina Yamada and Vandebroek, {Arno A.} and Masashi Mita and Kenji Hamase and Masato Yasui and Jumpei Sasabe",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-019-53302-2",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1

AU - Suzuki, Masataka

AU - Gonda, Yusuke

AU - Yamada, Marina

AU - Vandebroek, Arno A.

AU - Mita, Masashi

AU - Hamase, Kenji

AU - Yasui, Masato

AU - Sasabe, Jumpei

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85074960449&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074960449&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-53302-2

DO - 10.1038/s41598-019-53302-2

M3 - Article

C2 - 31723194

AN - SCOPUS:85074960449

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 16705

ER -