PMID- 24913063 OWN - NLM STAT- MEDLINE DCOM- 20150403 LR - 20140804 IS - 1096-7206 (Electronic) IS - 1096-7192 (Linking) VI - 112 IP - 4 DP - 2014 Aug TI - Methionine-induced hyperhomocysteinemia and bleomycin hydrolase deficiency alter the expression of mouse kidney proteins involved in renal disease. PG - 339-46 LID - S1096-7192(14)00172-3 [pii] LID - 10.1016/j.ymgme.2014.05.010 [doi] AB - 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. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Suszynska-Zajczyk, Joanna AU - Suszynska-Zajczyk J AD - Institute of Bioorganic Chemistry, Poznan, Poland. FAU - Utyro, Olga AU - Utyro O AD - Institute of Bioorganic Chemistry, Poznan, Poland; Department of Biochemistry and Biotechnology, University of Life Sciences, Poznan, Poland. FAU - Jakubowski, Hieronim AU - Jakubowski H AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140524 PL - United States TA - Mol Genet Metab JT - Molecular genetics and metabolism JID - 9805456 RN - 0 (Protein Isoforms) RN - 0 (Proteins) RN - AE28F7PNPL (Methionine) RN - EC 3.4.22.- (Cysteine Endopeptidases) RN - EC 3.4.22.40 (bleomycin hydrolase) RN - Homocysteinemia SB - IM MH - Animals MH - Blotting, Western MH - Cysteine Endopeptidases/*deficiency/genetics/metabolism MH - Diet MH - Electrophoresis, Polyacrylamide Gel MH - Gene Expression Regulation, Enzymologic MH - Genotype MH - Hyperhomocysteinemia/*enzymology/genetics/pathology MH - Isoelectric Focusing MH - Kidney/*metabolism MH - Kidney Diseases/*enzymology/*pathology MH - Methionine MH - Mice, Inbred C57BL MH - Protein Isoforms/metabolism MH - Proteins/*metabolism MH - Reproducibility of Results OTO - NOTNLM OT - Bleomycin hydrolase OT - Blmh-knockout mouse OT - Dietary hyperhomocysteinemia OT - High-methionine diet OT - Kidney disease OT - Mouse kidney proteome EDAT- 2014/06/11 06:00 MHDA- 2015/04/04 06:00 CRDT- 2014/06/11 06:00 PHST- 2014/04/10 00:00 [received] PHST- 2014/05/18 00:00 [revised] PHST- 2014/05/18 00:00 [accepted] PHST- 2014/06/11 06:00 [entrez] PHST- 2014/06/11 06:00 [pubmed] PHST- 2015/04/04 06:00 [medline] AID - S1096-7192(14)00172-3 [pii] AID - 10.1016/j.ymgme.2014.05.010 [doi] PST - ppublish SO - Mol Genet Metab. 2014 Aug;112(4):339-46. doi: 10.1016/j.ymgme.2014.05.010. Epub 2014 May 24.