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Amino Acids

, Volume 46, Issue 6, pp 1471–1480 | Cite as

Bleomycin hydrolase and hyperhomocysteinemia modulate the expression of mouse proteins involved in liver homeostasis

  • Joanna Suszyńska-Zajczyk
  • Jacek Wróblewski
  • Olga Utyro
  • Magdalena Łuczak
  • Łukasz Marczak
  • Hieronim JakubowskiEmail author
Original Article

Abstract

The liver is the major contributor to homocysteine (Hcy) metabolism and fatty liver disease is associated with hyperhomocysteinemia. Bleomycin hydrolase (Blmh) is an aminohydrolase that also participates in Hcy metabolism by hydrolyzing Hcy-thiolactone. To gain insight into hepatic functions of Blmh, we analyzed the liver proteome of Blmh −/− and Blmh +/+ mice in the absence and presence of diet-induced (high methionine) hyperhomocysteinemia using 2D IEF/SDS-PAGE gel electrophoresis and MALDI–TOF mass spectrometry. We identified eleven liver proteins whose expression was significantly altered as a result of the Blmh gene inactivation. The differential expression (Blmh −/− vs. Blmh +/+) of four liver proteins was lower, of two proteins was higher, and was further modified in mice fed with a hyperhomocysteinemic high-Met diet. The down-regulated proteins are involved in lipoprotein metabolism (ApoA1, ApoE), antigen processing (Psme1), energy metabolism (Atp5h, Gamt), methylglyoxal detoxification (Glo1), oxidative stress response (Sod1), and inactivation of catecholamine neurotransmitters (Comt). The two up-regulated proteins are involved in nitric oxide generation (Ddah1) and xenobiotic detoxification (Sult1c1). We also found that livers of Blmh −/− mice expressed a novel variant of glyoxalase domain-containing protein 4 (Glod4) by a post-transcriptional mechanism. Our findings suggest that Blmh interacts with diverse cellular processes—from lipoprotein metabolism, nitric oxide regulation, antigen processing, and energy metabolism to detoxification and antioxidant defenses—that are essential for liver homeostasis and that modulation of these interactions by hyperhomocysteinemia underlies the involvement of Hcy in fatty liver disease.

Keywords

Bleomycin hydrolase High methionine diet Hyperhomocysteinemia Mouse liver proteome 

Abbreviations

Hcy

Homocysteine

Blmh

Bleomycin hydrolase

Cbs

Cystathionine β-synthase

ApoA1

Apolipoprotein A1

ApoE

Apolipoprotein E

Psme1

Proteasome activator complex subunit 1

Atp5 h

ATPase subunit d

Gamt

Guanidinoacetate-N-methyltransferase

Glo1

Methylglyoxylase 1

Sod1

Superoxide dismutase

Comt

Catechol-O-methyltransferase

Ddah1

Dimethylarginine dimethylaminohydrolase 1

Sult1c1

Phenolsulphotransferase

IEF/SDS-PAGE

Isoelectric focusing/sodium dodecylsulphate polyacrylamide gel electrophoresis

MALDI–TOF

Matrix-assisted laser desorption ionization–time of flight

Notes

Acknowledgments

We thank John Lazo for kindly providing a breeding pair of Blmh-null mice. This work was supported in part by grants from the American Heart Association, the National Science Center, Poland (2011/01/B/NZ1/03417, 2011/02/A/NZ1/00010, 2012/07/B/NZ7/01178, and 2013/09/B/NZ5/02794) and MNiSW, Poland (N401 065321504, N N302 434439).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

726_2014_1712_MOESM1_ESM.docx (31 kb)
Supplementary material 1 (DOCX 30 kb)
726_2014_1712_MOESM2_ESM.docx (1.7 mb)
Supplementary material 2 (DOCX 1729 kb)
726_2014_1712_MOESM3_ESM.docx (40 kb)
Supplementary material 3 (DOCX 39 kb)

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Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Joanna Suszyńska-Zajczyk
    • 1
    • 3
  • Jacek Wróblewski
    • 1
  • Olga Utyro
    • 1
  • Magdalena Łuczak
    • 1
  • Łukasz Marczak
    • 1
  • Hieronim Jakubowski
    • 1
    • 2
    • 3
    Email author
  1. 1.Institute of Bioorganic ChemistryPoznańPoland
  2. 2.Department of Biochemistry and BiotechnologyUniversity of Life SciencesPoznańPoland
  3. 3.Department of Microbiology and Molecular GeneticsRutgers-New Jersey Medical School, International Center for Public HealthNewarkUSA

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