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

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.

• Authors: Joanna Suszyńska-Zajczyk, Olga Utyro, Hieronim Jakubowski
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 112 Issue 4 Pg. 339-46 (Aug 2014) ISSN: 1096-7206 [Electronic] United States
• PMID: 24913063 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Protein Isoforms
• Proteins
• Methionine
• Cysteine Endopeptidases
• bleomycin hydrolase

Topics

• Animals
• Blotting, Western
• Cysteine Endopeptidases (deficiency, genetics, metabolism)
• Diet
• Electrophoresis, Polyacrylamide Gel
• Gene Expression Regulation, Enzymologic
• Genotype
• Hyperhomocysteinemia (enzymology, genetics, pathology)
• Isoelectric Focusing
• Kidney (metabolism)
• Kidney Diseases (enzymology, pathology)
• Methionine
• Mice, Inbred C57BL
• Protein Isoforms (metabolism)
• Proteins (metabolism)
• Reproducibility of Results