TY - JOUR
T1 - Proteomic analysis of Rac1 transgenic mice displaying dilated cardiomyopathy reveals an increase in creatine kinase M-chain protein abundance
AU - Buscemi, Nina
AU - Doherty-Kirby, Amanda
AU - Sussman, Mark A.
AU - Lajoie, Gilles
AU - Van Eyk, Jennifer E.
N1 - Funding Information:
Dr. Jennifer Van Eyk is supported by Canadian Institutes of Health Research and the Heart and Stroke Foundation of Ontario. She is a Heart and Stroke Foundation of Canada Scholar and Nina Buscemi is a Heart and Stroke Foundation of Canada Trainee. Dr. Gilles Lajoie is funded by the National Sciences Research Council (NSERC) and the Ontario Research and Development Challenge Fund (ORDCF).
PY - 2003/9
Y1 - 2003/9
N2 - 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.
AB - 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.
KW - Heart failure
KW - Proteomics
KW - Rac1
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U2 - 10.1023/A:1025402520506
DO - 10.1023/A:1025402520506
M3 - Article
C2 - 14575316
AN - SCOPUS:0141839835
SN - 0300-8177
VL - 251
SP - 145
EP - 151
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -