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Tomin, T; Schittmayer, M; Sedej, S; Bugger, H; Gollmer, J; Honeder, S; Darnhofer, B; Liesinger, L; Zuckermann, A; Rainer, PP; Birner-Gruenberger, R.
Mass Spectrometry-Based Redox and Protein Profiling of Failing Human Hearts.
Int J Mol Sci. 2021; 22(4):
Doi: 10.3390/ijms22041787
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- Führende Autor*innen der Med Uni Graz
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Birner-Grünberger Ruth
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Rainer Peter
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Tomin Tamara
- Co-Autor*innen der Med Uni Graz
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Bugger Heiko Matthias
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Darnhofer Barbara
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Gollmer Johannes
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Honeder Sophie
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Liesinger Laura
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Schittmayer-Schantl Matthias
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Sedej Simon
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- Abstract:
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Oxidative stress contributes to detrimental functional decline of the myocardium, leading to the impairment of the antioxidative defense, dysregulation of redox signaling, and protein damage. In order to precisely dissect the changes of the myocardial redox state correlated with oxidative stress and heart failure, we subjected left-ventricular tissue specimens collected from control or failing human hearts to comprehensive mass spectrometry-based redox and quantitative proteomics, as well as glutathione status analyses. As a result, we report that failing hearts have lower glutathione to glutathione disulfide ratios and increased oxidation of a number of different proteins, including constituents of the contractile machinery as well as glycolytic enzymes. Furthermore, quantitative proteomics of failing hearts revealed a higher abundance of proteins responsible for extracellular matrix remodeling and reduced abundance of several ion transporters, corroborating contractile impairment. Similar effects were recapitulated by an in vitro cell culture model under a controlled oxygen atmosphere. Together, this study provides to our knowledge the most comprehensive report integrating analyses of protein abundance and global and peptide-level redox state in end-stage failing human hearts as well as oxygen-dependent redox and global proteome profiles of cultured human cardiomyocytes.
- Find related publications in this database (using NLM MeSH Indexing)
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Aged -
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Female -
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Gene Expression Profiling -
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Heart Failure - metabolism
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Heart Ventricles - metabolism
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Humans -
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Male -
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Mass Spectrometry -
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Middle Aged -
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Muscle Proteins - metabolism
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Myocardium - metabolism
- Find related publications in this database (Keywords)
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failing hearts
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cardiomyopathy
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oxidative stress
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redox proteomics