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Proteomic analysis of Rac1 transgenic mice displaying dilated cardiomyopathy reveals an increase in creatine kinase M-chain protein abundance

  • Nina Buscemi
  • Amanda Doherty-Kirby
  • Mark A. Sussman
  • Gilles Lajoie
  • Jennifer E. Van Eyk
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 43)

Abstract

Here, we demonstrate the application of the proteomic approach to the study of a transgenic mouse model of heart failure and provide an example of a disease-associated protein alteration that can be observed using this approach. Specifically, we applied the proteomic approach to the analysis of a mouse model of dilated cardiomyopathy in which the small GTPase, Rac1, was constitutively expressed specifically in the myocardium. We utilized the methods of two-dimensional gel electrophoresis (2-DE) for protein separation, silver-staining for protein visualization and mass spectrometry (MALDI-TOF and MS/MS) for protein spot identification. Computer-generated composite images were created which represent a normalized average of four 2-DE gel images derived from analysis of either Rac1 transgenic (n = 4) or non-transgenic (n = 4) mice. Analysis of composite images derived from NTG and Rac1 experimental groups revealed numerous statistically significant differences in mean protein spot intensities. Here, we report a statistically significant increase, of approximately 1.6-fold, in the mean protein spot intensity for creatine kinase M-chain in the composite image of Rac1 transgenic mice compared to control. This protein alteration may be consistent with an end-stage heart failure phenotype in which maximal myocardial reserve is employed to sustain survival.

Keywords

proteomics heart failure Rac1 

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Nina Buscemi
    • 1
  • Amanda Doherty-Kirby
    • 3
  • Mark A. Sussman
    • 4
  • Gilles Lajoie
    • 3
  • Jennifer E. Van Eyk
    • 1
    • 2
    • 5
  1. 1.Department of PhysiologyQueen’s UniversityKingstonCanada
  2. 2.Department of BiochemistryQueen’s UniversityKingstonCanada
  3. 3.Department of BiochemistryUniversity of Western Ontario, Siebens-Drake Research InstituteLondonCanada
  4. 4.The Children’s Hospital and Research Foundation, Division of Molecular and Cardiovascular BiologyCincinnatiUSA
  5. 5.Department of PhysiologyQueen’s UniversityKingstonCanada

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