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  Effects of mycophenolate mofetil on kidney function and phosphorylation status of renal proteins in Alport COL4A3-deficient mice.

Petrova, D. T., Schultze, F. C., Brandhorst, G., Luchs, K. D., Lenz, C., Urlaub, H., et al. (2014). Effects of mycophenolate mofetil on kidney function and phosphorylation status of renal proteins in Alport COL4A3-deficient mice. Proteome Science, 12: 56. doi:10.1186/s12953-014-0056-z.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-6CAD-4 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-CCBF-D
Genre: Journal Article

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 Creators:
Petrova, D. T., Author
Schultze, F. C., Author
Brandhorst, G., Author
Luchs, K. D., Author
Lenz, C., Author
Urlaub, H.1, Author              
Rubel, D., Author
Gross, O., Author
Walson, P. D., Author
Oellerich, M., Author
Affiliations:
1Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              

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Free keywords: Mycophenolic acid; Kidney fibrosis; Protein phosphorylation; Alport syndrome
 Abstract: Background: We investigated the effects of mycophenolate mofetil (MMF) on kidney function and on protein phosphorylation in a mouse model for the human Alport syndrome. Methods: COL4A3-deficient (COL4A3-/-) mice were randomly allocated to receive a placebo (PLC COL4A3-/-) or MMF treatment (MMF COL4A3-/-). Wild type mice (WT) were used as controls. Changes in serum creatinine, total protein and blood urea nitrogen (BUN), concentrations of mycophenolic acid (MPA) and its glucuronide metabolite (MPAG), serum protein electrophoresis, urine dipstick chemistry and sediment were measured. Changes in the phosphorylation status of renal proteins and histology were analyzed. Results: MMF influenced kidney function and protein phosphorylation. Serum creatinine and BUN were lower in MMF treated compared to PLC treated COL4A3-/-mice. Serum albumin and alpha-1 globulins were significantly decreased while serum creatinine, alpha-2 globulins, urine dipstick protein, leukocyte esterase, hemoglobin and red blood cells were all increased in both COL4A3-/-groups compared to WT. Differential 2DE-gel analysis identified six phosphorylated kidney protein spots that were significantly altered by MMF. Conclusions: These data suggest that the MMF treatment in this murine model moderately improved kidney function and reversed the phosphorylation status of six renal phosphoprotein spots to that seen in WT mice.

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Language(s): eng - English
 Dates: 2014-12-10
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.1186/s12953-014-0056-z
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Title: Proteome Science
Source Genre: Journal
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Pages: 10 Volume / Issue: 12 Sequence Number: 56 Start / End Page: - Identifier: -