| First Author | Suszyńska-Zajczyk J | Year | 2014 |
| Journal | Mol Genet Metab | Volume | 112 |
| Issue | 4 | Pages | 339-46 |
| PubMed ID | 24913063 | Mgi Jnum | J:219444 |
| Mgi Id | MGI:5620840 | Doi | 10.1016/j.ymgme.2014.05.010 |
| Citation | Suszynska-Zajczyk J, et al. (2014) Methionine-induced hyperhomocysteinemia and bleomycin hydrolase deficiency alter the expression of mouse kidney proteins involved in renal disease. Mol Genet Metab 112(4):339-46 |
| abstractText | 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. |
