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Glycoconjugate Journal

, Volume 36, Issue 1, pp 1–11 | Cite as

Impact of chronic kidney dysfunction on serum Sulfatides and its metabolic pathway in mice

  • Yosuke Yamada
  • Makoto Harada
  • Koji Hashimoto
  • Ran Guo
  • Takero Nakajima
  • Toshihide Kashihara
  • Mitsuhiko Yamada
  • Toshifumi Aoyama
  • Yuji KamijoEmail author
Original Article
  • 92 Downloads

Abstract

Serum sulfatides are critical glycosphingolipids that are present in lipoproteins and exert anticoagulant effects. A previous study reported decreased levels of serum sulfatides in hemodialysis patients and suggested an association with cardiovascular disease. However, the mechanism of changes in serum sulfatides in chronic kidney dysfunction has not been well investigated. The current study examined whether a chronic kidney disease (CKD) state could decrease serum sulfatide levels using 5/6 nephrectomy (5/6NCKD) mice, an established CKD murine model, and studied the mechanisms contributing to diminished sulfatides. 5/6NCKD mice and sham operation control mice were sacrificed at the 4th or 12th postoperative week (POW) for measurement of serum sulfatide levels. Hepatic sulfatide content, which is the origin of serum sulfatides, and the expression of sulfatide metabolic enzymes in liver tissue were assessed as well. The 5/6NCKD mice developed CKD and showed increased serum creatinine and indoxyl sulfate. The serum levels and hepatic amounts of sulfatides were significantly decreased in 5/6NCKD mice at both 4 and 12 POW, while the degradative enzymes of sulfatides arylsulfatase A and galactosylceramidase were significantly increased. In a Hepa1–6 murine liver cell line, indoxyl sulfate addition caused intracellular levels of sulfatides to decrease and degradative enzymes of sulfatides to increase in a manner comparable to the changes in 5/6NCKD mice liver tissue. In conclusion, chronic kidney dysfunction causes degradation of sulfatides in the liver to decrease serum sulfatide levels. One explanation of these results is that indoxyl sulfate, a uremic toxin, accelerates the degradation of sulfatides in liver tissue.

Keywords

Sulfatides Chronic kidney disease 5/6 nephrectomy model Indoxyl sulfate 

Abbreviations

ACOX

Acyl-CoA oxidase

AKI

Acute kidney injury

ARSA

Arylsulfatase A

CAT

Catalase

CGT

Ceramide galactosyltransferase

CKD

Chronic kidney disease

COX2

Cyclooxygenase-2

CST

Cerebroside sulfotransferase

CVD

Cardiovascular disease

ESRD

End-stage renal disease

GALC

Galactosylceramidase

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

HD

Hemodialysis

HNE

4-hydroxynonenal

IS

Indoxyl sulfate

LS

Lysosulfatides

MALDI-TOF MS

Matrix-assisted laser desorption ionization-time of flight mass spectrometry

MDA

Malondialdehyde

mRNA

Messenger ribonucleic acid

NOX2

Nonphagocytic oxidase-2

PBS

Phosphate buffered saline

qPCR

Quantitative real-time polymerase chain reaction

POW

Postoperative week

SPT

Serine palmitoyl-CoA transferase

TNFα

Tumor necrosis factor-α

5/6NCKD

5/6 nephrectomy chronic kidney disease

Notes

Acknowledgments

This study was supported by a grant-in-aid for Scientific Research (KAKENHI) in Japan (grant number: 18 K08204).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

10719_2018_9850_MOESM1_ESM.pdf (522 kb)
ESM 1 (PDF 521 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yosuke Yamada
    • 1
    • 2
  • Makoto Harada
    • 2
  • Koji Hashimoto
    • 2
  • Ran Guo
    • 1
  • Takero Nakajima
    • 1
    • 3
  • Toshihide Kashihara
    • 4
  • Mitsuhiko Yamada
    • 4
  • Toshifumi Aoyama
    • 1
  • Yuji Kamijo
    • 1
    • 2
    Email author
  1. 1.Department of Metabolic RegulationShinshu University School of MedicineNaganoJapan
  2. 2.Department of NephrologyShinshu University School of MedicineNaganoJapan
  3. 3.Research Center for Agricultural Food IndustryShinshu UniversityNaganoJapan
  4. 4.Department of Molecular PharmacologyShinshu University School of MedicineNaganoJapan

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