Mass Spectrometry-Based Redox and Protein Profiling of Failing Human Hearts
Open Access
- 11 February 2021
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (4), 1787
- https://doi.org/10.3390/ijms22041787
Abstract
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.Funding Information
- Austrian Science Fund (KLI425, KLI645, W1266, F73)
- Austrian Ministry of Science, Research and Economy (Omics Center Graz, 201901)
This publication has 74 references indexed in Scilit:
- Cardiac Metabolism in Heart FailureCirculation Research, 2013
- Rheb is a Critical Regulator of Autophagy During Myocardial IschemiaCirculation, 2012
- Oxidative stress and heart failureAmerican Journal of Physiology-Heart and Circulatory Physiology, 2011
- Andromeda: A Peptide Search Engine Integrated into the MaxQuant EnvironmentJournal of Proteome Research, 2011
- MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in miceJCI Insight, 2010
- A comparison of batch effect removal methods for enhancement of prediction performance using MAQC-II microarray gene expression dataThe Pharmacogenomics Journal, 2010
- Glutathione Deficiency in Cardiac Patients Is Related to the Functional Status and Structural Cardiac AbnormalitiesPLOS ONE, 2009
- MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantificationNature Biotechnology, 2008
- Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular massNature Genetics, 2008
- Induction of myocardial biglycan in heart failure in rats—an extracellular matrix component targeted by AT1 receptor antagonismCardiovascular Research, 2003