Ischemic acute kidney injury perturbs homeostasis of serine enantiomers in the body fluid in mice: Early detection of renal dysfunction using the ratio of serine enantiomers

Jumpei Sasabe, Masataka Suzuki, Yurika Miyoshi, Yosuke Tojo, Chieko Okamura, Sonomi Ito, Ryuichi Konno, Masashi Mita, Kenji Hamase, Sadakazu Aiso

研究成果: ジャーナルへの寄稿記事

24 引用 (Scopus)

抄録

The imbalance of blood and urine amino acids in renal failure has been studied mostly without chiral separation. Although a few reports have shown the presence of D-serine, an enantiomer of L-serine, in the serum of patients with severe renal failure, it has remained uncertain how serine enantiomers are deranged in the development of renal failure. In the present study, we have monitored serine enantiomers using a two-dimensional HPLC system in the serum and urine of mice after renal ischemia-reperfusion injury (IRI), known as a mouse model of acute kidney injury. In the serum, the level of D-serine gradually increased after renal IRI in parallel with that of creatinine, whereas the L-serine level decreased sharply in the early phase after IRI. The increase of D-serine was suppressed in part by genetic inactivation of a D-serine-degrading enzyme, D-amino acid oxidase (DAO), but not by disruption of its synthetic enzyme, serine racemase, in mice. Renal DAO activity was detected exclusively in proximal tubules, and IRI reduced the number of DAO-positive tubules. On the other hand, in the urine, D-serine was excreted at a rate nearly triple that of L-serine in mice with sham operations, indicating that little Dserine was reabsorbed while most L-serine was reabsorbed in physiological conditions. IRI significantly reduced the ratio of urinary D-/L-serine from 2.82±0.18 to 1.10±0.26 in the early phase and kept the ratio lower than 0.5 thereafter. The urinary D-/L-serine ratio can detect renal ischemia earlier than kidney injury molecule-1 (KIM-1) or neutrophil gelatinase- associated lipocalin (NGAL) in the urine, and more sensitively than creatinine, cystatin C, or the ratio of D-/L-serine in the serum. Our findings provide a novel understanding of the imbalance of amino acids in renal failure and offer a potential new biomarker for an early detection of acute kidney injury.

元の言語英語
記事番号e86504
ジャーナルPloS one
9
発行部数1
DOI
出版物ステータス出版済み - 1 29 2014

Fingerprint

Enantiomers
body fluids
Body fluids
enantiomers
Body Fluids
Acute Kidney Injury
serine
Serine
homeostasis
Homeostasis
kidneys
Kidney
mice
ischemia
Reperfusion Injury
D-Amino-Acid Oxidase
renal failure
Renal Insufficiency
urine
Urine

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

これを引用

Ischemic acute kidney injury perturbs homeostasis of serine enantiomers in the body fluid in mice : Early detection of renal dysfunction using the ratio of serine enantiomers. / Sasabe, Jumpei; Suzuki, Masataka; Miyoshi, Yurika; Tojo, Yosuke; Okamura, Chieko; Ito, Sonomi; Konno, Ryuichi; Mita, Masashi; Hamase, Kenji; Aiso, Sadakazu.

:: PloS one, 巻 9, 番号 1, e86504, 29.01.2014.

研究成果: ジャーナルへの寄稿記事

Sasabe, Jumpei ; Suzuki, Masataka ; Miyoshi, Yurika ; Tojo, Yosuke ; Okamura, Chieko ; Ito, Sonomi ; Konno, Ryuichi ; Mita, Masashi ; Hamase, Kenji ; Aiso, Sadakazu. / Ischemic acute kidney injury perturbs homeostasis of serine enantiomers in the body fluid in mice : Early detection of renal dysfunction using the ratio of serine enantiomers. :: PloS one. 2014 ; 巻 9, 番号 1.
@article{b3fef9ee9f8348c596691a15c39cf67e,
title = "Ischemic acute kidney injury perturbs homeostasis of serine enantiomers in the body fluid in mice: Early detection of renal dysfunction using the ratio of serine enantiomers",
abstract = "The imbalance of blood and urine amino acids in renal failure has been studied mostly without chiral separation. Although a few reports have shown the presence of D-serine, an enantiomer of L-serine, in the serum of patients with severe renal failure, it has remained uncertain how serine enantiomers are deranged in the development of renal failure. In the present study, we have monitored serine enantiomers using a two-dimensional HPLC system in the serum and urine of mice after renal ischemia-reperfusion injury (IRI), known as a mouse model of acute kidney injury. In the serum, the level of D-serine gradually increased after renal IRI in parallel with that of creatinine, whereas the L-serine level decreased sharply in the early phase after IRI. The increase of D-serine was suppressed in part by genetic inactivation of a D-serine-degrading enzyme, D-amino acid oxidase (DAO), but not by disruption of its synthetic enzyme, serine racemase, in mice. Renal DAO activity was detected exclusively in proximal tubules, and IRI reduced the number of DAO-positive tubules. On the other hand, in the urine, D-serine was excreted at a rate nearly triple that of L-serine in mice with sham operations, indicating that little Dserine was reabsorbed while most L-serine was reabsorbed in physiological conditions. IRI significantly reduced the ratio of urinary D-/L-serine from 2.82±0.18 to 1.10±0.26 in the early phase and kept the ratio lower than 0.5 thereafter. The urinary D-/L-serine ratio can detect renal ischemia earlier than kidney injury molecule-1 (KIM-1) or neutrophil gelatinase- associated lipocalin (NGAL) in the urine, and more sensitively than creatinine, cystatin C, or the ratio of D-/L-serine in the serum. Our findings provide a novel understanding of the imbalance of amino acids in renal failure and offer a potential new biomarker for an early detection of acute kidney injury.",
author = "Jumpei Sasabe and Masataka Suzuki and Yurika Miyoshi and Yosuke Tojo and Chieko Okamura and Sonomi Ito and Ryuichi Konno and Masashi Mita and Kenji Hamase and Sadakazu Aiso",
year = "2014",
month = "1",
day = "29",
doi = "10.1371/journal.pone.0086504",
language = "English",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Ischemic acute kidney injury perturbs homeostasis of serine enantiomers in the body fluid in mice

T2 - Early detection of renal dysfunction using the ratio of serine enantiomers

AU - Sasabe, Jumpei

AU - Suzuki, Masataka

AU - Miyoshi, Yurika

AU - Tojo, Yosuke

AU - Okamura, Chieko

AU - Ito, Sonomi

AU - Konno, Ryuichi

AU - Mita, Masashi

AU - Hamase, Kenji

AU - Aiso, Sadakazu

PY - 2014/1/29

Y1 - 2014/1/29

N2 - The imbalance of blood and urine amino acids in renal failure has been studied mostly without chiral separation. Although a few reports have shown the presence of D-serine, an enantiomer of L-serine, in the serum of patients with severe renal failure, it has remained uncertain how serine enantiomers are deranged in the development of renal failure. In the present study, we have monitored serine enantiomers using a two-dimensional HPLC system in the serum and urine of mice after renal ischemia-reperfusion injury (IRI), known as a mouse model of acute kidney injury. In the serum, the level of D-serine gradually increased after renal IRI in parallel with that of creatinine, whereas the L-serine level decreased sharply in the early phase after IRI. The increase of D-serine was suppressed in part by genetic inactivation of a D-serine-degrading enzyme, D-amino acid oxidase (DAO), but not by disruption of its synthetic enzyme, serine racemase, in mice. Renal DAO activity was detected exclusively in proximal tubules, and IRI reduced the number of DAO-positive tubules. On the other hand, in the urine, D-serine was excreted at a rate nearly triple that of L-serine in mice with sham operations, indicating that little Dserine was reabsorbed while most L-serine was reabsorbed in physiological conditions. IRI significantly reduced the ratio of urinary D-/L-serine from 2.82±0.18 to 1.10±0.26 in the early phase and kept the ratio lower than 0.5 thereafter. The urinary D-/L-serine ratio can detect renal ischemia earlier than kidney injury molecule-1 (KIM-1) or neutrophil gelatinase- associated lipocalin (NGAL) in the urine, and more sensitively than creatinine, cystatin C, or the ratio of D-/L-serine in the serum. Our findings provide a novel understanding of the imbalance of amino acids in renal failure and offer a potential new biomarker for an early detection of acute kidney injury.

AB - The imbalance of blood and urine amino acids in renal failure has been studied mostly without chiral separation. Although a few reports have shown the presence of D-serine, an enantiomer of L-serine, in the serum of patients with severe renal failure, it has remained uncertain how serine enantiomers are deranged in the development of renal failure. In the present study, we have monitored serine enantiomers using a two-dimensional HPLC system in the serum and urine of mice after renal ischemia-reperfusion injury (IRI), known as a mouse model of acute kidney injury. In the serum, the level of D-serine gradually increased after renal IRI in parallel with that of creatinine, whereas the L-serine level decreased sharply in the early phase after IRI. The increase of D-serine was suppressed in part by genetic inactivation of a D-serine-degrading enzyme, D-amino acid oxidase (DAO), but not by disruption of its synthetic enzyme, serine racemase, in mice. Renal DAO activity was detected exclusively in proximal tubules, and IRI reduced the number of DAO-positive tubules. On the other hand, in the urine, D-serine was excreted at a rate nearly triple that of L-serine in mice with sham operations, indicating that little Dserine was reabsorbed while most L-serine was reabsorbed in physiological conditions. IRI significantly reduced the ratio of urinary D-/L-serine from 2.82±0.18 to 1.10±0.26 in the early phase and kept the ratio lower than 0.5 thereafter. The urinary D-/L-serine ratio can detect renal ischemia earlier than kidney injury molecule-1 (KIM-1) or neutrophil gelatinase- associated lipocalin (NGAL) in the urine, and more sensitively than creatinine, cystatin C, or the ratio of D-/L-serine in the serum. Our findings provide a novel understanding of the imbalance of amino acids in renal failure and offer a potential new biomarker for an early detection of acute kidney injury.

UR - http://www.scopus.com/inward/record.url?scp=84900397811&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84900397811&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0086504

DO - 10.1371/journal.pone.0086504

M3 - Article

C2 - 24489731

AN - SCOPUS:84900397811

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e86504

ER -