The Interplay between S-Glutathionylation and Phosphorylation of Cardiac Troponin I and Myosin Binding Protein C in End-Stage Human Failing Hearts Article Swipe
Heidi Budde
,
Roua Hassoun
,
Melina Tangos
,
Saltanat Zhazykbayeva
,
Melissa Herwig
,
Marharyta Varatnitskaya
,
Marcel Sieme
,
Simin Delalat
,
Innas Sultana
,
Detmar Kolijn
,
Kamilla Gömöri
,
Muhammad Jarkas
,
Mária Lódi
,
Kornélia Jaquet
,
Árṕad Kov́acs
,
Hans Georg Mannherz
,
Vasco Sequeira
,
Andreas Mügge
,
Lars I. Leichert
,
Samuel Sossalla
,
Nazha Hamdani
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/antiox10071134
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/antiox10071134
Oxidative stress is defined as an imbalance between the antioxidant defense system and the production of reactive oxygen species (ROS). At low levels, ROS are involved in the regulation of redox signaling for cell protection. However, upon chronical increase in oxidative stress, cell damage occurs, due to protein, DNA and lipid oxidation. Here, we investigated the oxidative modifications of myofilament proteins, and their role in modulating cardiomyocyte function in end-stage human failing hearts. We found altered maximum Ca2+-activated tension and Ca2+ sensitivity of force production of skinned single cardiomyocytes in end-stage human failing hearts compared to non-failing hearts, which was corrected upon treatment with reduced glutathione enzyme. This was accompanied by the increased oxidation of troponin I and myosin binding protein C, and decreased levels of protein kinases A (PKA)- and C (PKC)-mediated phosphorylation of both proteins. The Ca2+ sensitivity and maximal tension correlated strongly with the myofilament oxidation levels, hypo-phosphorylation, and oxidative stress parameters that were measured in all the samples. Furthermore, we detected elevated titin-based myocardial stiffness in HF myocytes, which was reversed by PKA and reduced glutathione enzyme treatment. Finally, many oxidative stress and inflammation parameters were significantly elevated in failing hearts compared to non-failing hearts, and corrected upon treatment with the anti-oxidant GSH enzyme. Here, we provide evidence that the altered mechanical properties of failing human cardiomyocytes are partially due to phosphorylation, S-glutathionylation, and the interplay between the two post-translational modifications, which contribute to the development of heart failure.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/antiox10071134
- https://www.mdpi.com/2076-3921/10/7/1134/pdf?version=1626688036
- OA Status
- gold
- Cited By
- 24
- References
- 76
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3186763920
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3186763920Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/antiox10071134Digital Object Identifier
- Title
-
The Interplay between S-Glutathionylation and Phosphorylation of Cardiac Troponin I and Myosin Binding Protein C in End-Stage Human Failing HeartsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-07-16Full publication date if available
- Authors
-
Heidi Budde, Roua Hassoun, Melina Tangos, Saltanat Zhazykbayeva, Melissa Herwig, Marharyta Varatnitskaya, Marcel Sieme, Simin Delalat, Innas Sultana, Detmar Kolijn, Kamilla Gömöri, Muhammad Jarkas, Mária Lódi, Kornélia Jaquet, Árṕad Kov́acs, Hans Georg Mannherz, Vasco Sequeira, Andreas Mügge, Lars I. Leichert, Samuel Sossalla, Nazha HamdaniList of authors in order
- Landing page
-
https://doi.org/10.3390/antiox10071134Publisher landing page
- PDF URL
-
https://www.mdpi.com/2076-3921/10/7/1134/pdf?version=1626688036Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/2076-3921/10/7/1134/pdf?version=1626688036Direct OA link when available
- Concepts
-
Oxidative stress, Myofilament, Oxidative phosphorylation, Phosphorylation, Reactive oxygen species, Myosin, Glutathione, Cell biology, Chemistry, Protein kinase C, Troponin I, Myocyte, Internal medicine, Biochemistry, Biology, Enzyme, Medicine, Myocardial infarctionTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
24Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 6, 2024: 4, 2023: 5, 2022: 9Per-year citation counts (last 5 years)
- References (count)
-
76Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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