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1 Physiology, Queen's University, Kingston, Ontario, Canada
2 Biochemistry, University of Western Ontario, London, Ontario, Canada
3 Molecular and Cardiovascular Biology, The Children's Hospital and Research Foundation, Cincinnati, Ohio, USA
4 Physiology, Queen's University, Kingston, Ontario, Canada; Biochemistry, Queen's University, Kingston, Ontario, Canada
* To whom correspondence should be addressed. E-mail: jvaneyk1{at}jhmi.edu.
A two-dimensional gel electrophoresis (2-DE)-based proteomic approach was used to study a transgenic mouse model of acerbated dilated cardiomyopathy in which the small monomeric GTPase, Rac1, was constitutively expressed exclusively in the myocardium. A sub-fractionation procedure allowed for the focused analysis of both cytoplasmic and myofilament protein-enriched extracts of ventricular tissue from Rac1 transgenic and age-matched non-transgenic (NTG) mice. The majority of these mice displayed severe hypertrophy (heart-to-body weight ratios over 2 fold greater in the Rac1 mice) and died from overt heart failure between day 14-17. Comparative 2-DE analysis (pH 3-10, 12% SDS-PAGE) derived from Rac1 (n=4) and NTG (n=4) groups revealed differences in mean protein spot intensities. Twelve proteins from the cytoplasmic protein-enriched extract met our criteria for robustness and spot resolution, and were identified. These proteins represent a broad distribution of cellular functions with only some previously implicated in myocardial hypertrophy. The myofilament subproteome displayed no change in post-translational modification, but further analysis by one-dimensional Western blot showed increased quantities of myofilament proteins in the Rac1 mouse ventricles. Additionally, three proteins with different functionality that were altered in the cytoplasmic enriched subproteome, tubulin 
chain, manganese superoxide dismutase and malate dehydrogenase were analyzed at day 7, 9 and 11 to assess their role in the development of the dilated cardiomyopathic phenotype. The quantity of all three proteins peaked at day 9, suggesting an early response in cardiac hypertrophic failure.
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