Sex differences in the cardiac proteome in myocardial hypertrophy
Final Report Abstract
We investigated the proteome of the heart of mouse Chromosome Substitution Strains (Consomic Strains, CS). The CS mouse lines were strain C57BL/6J (B6), but one pair of chromosomes in each strain came from the PWD/Ph strain. We compared the proteins of the heart from 10 CSs versus B6 using 2-D electrophoresis. Our aim was to investigate the effect of the polymorphisms, which were transferred by the PWD chromosome into B6, on the proteome network. In recent publications it has been shown that polymorphisms affect the protein network of the cell and that this may initiate complex diseases, such as heart hypertrophy. In males/females we detected in the 10 CSs 364/375 quantitative protein variants. Out of these151/175 were identified by mass spectrometry. Two observations were unexpected and of particular interest. 1.- One would expect that the variant proteins in the CSs are cis-variants and come from genes of the PWD chromosome. However, most of the variant proteins mapped on B6-chromosomes. Apparently, by the protein-protein interactions in the proteome network, proteins became trans-variant by the cis-variant proteins and furthermore by trans-trans interactions. On the average the cis-trans relationship was in males 1/10, in females 1/16. 2.- The total number of variant proteins differed considerably between the CSs: males: 26 to 69, females: 12 to 80 (but correlated significantly between males and females). Our conclusion was that a high number of trans-variant proteins indicates low perturbation of the protein network by polymorphisms and this may indicate individuals with a proteome network of high robustness. This was confirmed when we induced heart hypertrophy in CSs: High trans-variability apparently protected from the disease.
Publications
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Heart protein expression related to age and sex in mice an human. Int J Mol Med. 20: 865-874, 2007
Diedrich M, Tadic J, Mao J, Wacker MA, Nebrich G, Hetzer R, Regitz-Zagrosek V, Klose J
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Comparative proteomic analysis reveals sex and estrogen receptor ß effects in the pressure overloaded heart. Journal of Proteome Research
Kararigas G, Fliegner D, Forler S, Schubert C, Gustafsson J, Klose J, Regitz- Zagrosek V
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Individualized proteomics. Journal of Proteomics 107: 56-61, 2014
Forler S, Klein O, Klose J
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Investigation of the heart proteome of different consomic mouse strains: Testing the effect of polymorphisms on the proteomewide trans-variation of proteins. EuPA Open Proteomics, 7:27-42, 2015
Forler S, Klein O, Koehler S, Robinson P, Witt H, Sultan M, Eravci M, Regitz- Zagrosek V, Lehrach H, Klose J
