title: Methionine-induced hyperhomocysteinemia and bleomycin hydrolase deficiency alter the expression of mouse kidney proteins involved in renal disease.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Institute of Bioorganic Chemistry, Poznan, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Suszyńska-Zajczyk
authors.affiliation: Institute of Bioorganic Chemistry, Poznan, Poland; Department of Biochemistry and Biotechnology, University of Life Sciences, Poznan, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Utyro
authors.affiliation: Institute of Bioorganic Chemistry, Poznan, Poland; Department of Biochemistry and Biotechnology, University of Life Sciences, Poznan, Poland; Department of Microbiology & Molecular Genetics, Rutgers-New Jersey Medical School, International Center for Public Health, Newark, NJ, USA. Electronic address: jakubows@njms.rutgers.edu.
authors.forename: Hieronim
authors.initials: H
authors.lastname: Jakubowski
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003546:Cysteine Endopeptidases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D004032:Diet; D004591:Electrophoresis, Polyacrylamide Gel; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D020138:Hyperhomocysteinemia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007525:Isoelectric Focusing; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000201:enzymology* / Q000473:pathology*; D008715:Methionine; D008810:Mice, Inbred C57BL; D020033:Protein Isoforms / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D020033:Protein Isoforms; D011506:Proteins; D008715:Methionine; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase
keywords: Bleomycin hydrolase; Blmh-knockout mouse; Dietary hyperhomocysteinemia; High-methionine diet; Kidney disease; Mouse kidney proteome