Methionine-induced hyperhomocysteinemia and bleomycin hydrolase deficiency alter the expression of mouse kidney proteins involved in renal disease

Joanna Suszyńska-Zajczyk, Olga Utyro, Hieronim Jakubowski

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Scope: Hyperhomocysteinemia (HHcy) induced by dietary or genetic factors is linked to kidney disease. Bleomycin hydrolase (Blmh) metabolizes Hcy-thiolactone to Hcy. We aimed to explain the role of dietary HHcy in kidney disease. Methods and results: We examined kidney proteome in dietary HHcy and Blmh-knockout mouse models using 2D IEF/SDS-PAGE gel electrophoresis and MALDI-TOF mass spectrometry. We found that the kidney proteome was altered by dietary HHcy and the Blmh-/- genotype. Proteins involved in metabolism of lipoprotein (ApoA1), amino acid and protein (Acy1, Hspd1), carbohydrate (Pdhb, Fbp1-isoform 1, Eno1), and energy metabolism (Ndufs8, Ldhd) were down-regulated. Proteins involved in carbohydrate metabolism (Fbp1-isoform 2), oxidative stress response (Prdx2), and detoxification (Glod4) were up-regulated. The Blmh-/- genotype down-regulated Glod4 isoform 3 mRNA but did not affect isoform 1 mRNA expression in mouse kidneys, suggesting post-transcriptional regulation of the Glod4 protein by the Blmh+/+ genotype. Responses of ApoA1, Acy1, Hspd1, Ndufs8, Fbp1, Eno1, and Prdx2 to HHcy and/or Blmh deficiency mimic their responses to renal disease. Conclusion: Our findings indicate that Blmh interacts with diverse cellular processes - lipoprotein, amino acid and protein, carbohydrate, and energy metabolisms, detoxification, antioxidant defenses - that are essential for normal kidney homeostasis and that deregulation of these processes can account for the involvement of HHcy in kidney disease.

Original languageEnglish (US)
Pages (from-to)339-346
Number of pages8
JournalMolecular Genetics and Metabolism
Volume112
Issue number4
DOIs
StatePublished - Aug 2014

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Keywords

  • Bleomycin hydrolase
  • Blmh-knockout mouse
  • Dietary hyperhomocysteinemia
  • High-methionine diet
  • Kidney disease
  • Mouse kidney proteome

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