Altered Cellular Protein Quality Control System Modulates Cardiomyocyte Function in Volume Overload-Induced Hypertrophy
Volume-induced hypertrophy is one of the risk factors for cardiac morbidity and mortality. In addition, mechanical and metabolic dysfunction, aging, and cellular redox balance are also contributing factors to the disease progression. In this study, we used volume overload (VO), which was induced by...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/11/2210 |
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| author | Kamilla Gömöri Melissa Herwig Roua Hassoun Heidi Budde Nusratul Mostafi Simin Delalat Suvasini Modi Merima Begovic Tamara Szabados Judit Pipis Nikolett Farkas-Morvay István Leprán Árpád Kovács Andreas Mügge Péter Ferdinandy Anikó Görbe Péter Bencsik Nazha Hamdani |
| author_facet | Kamilla Gömöri Melissa Herwig Roua Hassoun Heidi Budde Nusratul Mostafi Simin Delalat Suvasini Modi Merima Begovic Tamara Szabados Judit Pipis Nikolett Farkas-Morvay István Leprán Árpád Kovács Andreas Mügge Péter Ferdinandy Anikó Görbe Péter Bencsik Nazha Hamdani |
| author_sort | Kamilla Gömöri |
| collection | DOAJ |
| description | Volume-induced hypertrophy is one of the risk factors for cardiac morbidity and mortality. In addition, mechanical and metabolic dysfunction, aging, and cellular redox balance are also contributing factors to the disease progression. In this study, we used volume overload (VO), which was induced by an aortocaval fistula in 2-month-old male Wistar rats, and sham-operated animals served as control. Functional parameters were measured by transthoracic echocardiography at termination 4- or 8-months after VO. The animals showed hypertrophic remodeling that was accompanied by mechanical dysfunction and increased cardiomyocyte stiffness. These alterations were reversible upon treatment with glutathione. Cardiomyocyte dysfunction was associated with elevated oxidative stress markers with unchanged inflammatory signaling pathways. In addition, we observed altered phosphorylation status of small heat shock proteins 27 and 70 and diminished protease expression caspases 3 compared to the matched control group, indicating an impaired protein quality control system. Such alterations might be attributed to the increased oxidative stress as anticipated from the enhanced titin oxidation, ubiquitination, and the elevation in oxidative stress markers. Our study showed an early pathological response to VO, which manifests in cardiomyocyte mechanical dysfunction and dysregulated signaling pathways associated with enhanced oxidative stress and an impaired protein quality control system. |
| first_indexed | 2024-03-09T19:18:46Z |
| format | Article |
| id | doaj.art-12d16e342b124b6cb9013c40cb2f47ae |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T19:18:46Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-12d16e342b124b6cb9013c40cb2f47ae2023-11-24T03:31:01ZengMDPI AGAntioxidants2076-39212022-11-011111221010.3390/antiox11112210Altered Cellular Protein Quality Control System Modulates Cardiomyocyte Function in Volume Overload-Induced HypertrophyKamilla Gömöri0Melissa Herwig1Roua Hassoun2Heidi Budde3Nusratul Mostafi4Simin Delalat5Suvasini Modi6Merima Begovic7Tamara Szabados8Judit Pipis9Nikolett Farkas-Morvay10István Leprán11Árpád Kovács12Andreas Mügge13Péter Ferdinandy14Anikó Görbe15Péter Bencsik16Nazha Hamdani17Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Pharmacology and Pharmacotherapy, University of Szeged, HU-6720 Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, HU-6720 Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, HU-6720 Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, HU-6720 Szeged, HungaryDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Cardiology, St. Josef-Hospital, Ruhr University Bochum, 44801 Bochum, GermanyPharmahungary Group, HU-6720 Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, HU-6720 Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Szeged, HU-6720 Szeged, HungaryDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801 Bochum, GermanyVolume-induced hypertrophy is one of the risk factors for cardiac morbidity and mortality. In addition, mechanical and metabolic dysfunction, aging, and cellular redox balance are also contributing factors to the disease progression. In this study, we used volume overload (VO), which was induced by an aortocaval fistula in 2-month-old male Wistar rats, and sham-operated animals served as control. Functional parameters were measured by transthoracic echocardiography at termination 4- or 8-months after VO. The animals showed hypertrophic remodeling that was accompanied by mechanical dysfunction and increased cardiomyocyte stiffness. These alterations were reversible upon treatment with glutathione. Cardiomyocyte dysfunction was associated with elevated oxidative stress markers with unchanged inflammatory signaling pathways. In addition, we observed altered phosphorylation status of small heat shock proteins 27 and 70 and diminished protease expression caspases 3 compared to the matched control group, indicating an impaired protein quality control system. Such alterations might be attributed to the increased oxidative stress as anticipated from the enhanced titin oxidation, ubiquitination, and the elevation in oxidative stress markers. Our study showed an early pathological response to VO, which manifests in cardiomyocyte mechanical dysfunction and dysregulated signaling pathways associated with enhanced oxidative stress and an impaired protein quality control system.https://www.mdpi.com/2076-3921/11/11/2210volume overloadhypertrophyoxidative stressheat shock proteinsprotein quality control |
| spellingShingle | Kamilla Gömöri Melissa Herwig Roua Hassoun Heidi Budde Nusratul Mostafi Simin Delalat Suvasini Modi Merima Begovic Tamara Szabados Judit Pipis Nikolett Farkas-Morvay István Leprán Árpád Kovács Andreas Mügge Péter Ferdinandy Anikó Görbe Péter Bencsik Nazha Hamdani Altered Cellular Protein Quality Control System Modulates Cardiomyocyte Function in Volume Overload-Induced Hypertrophy Antioxidants volume overload hypertrophy oxidative stress heat shock proteins protein quality control |
| title | Altered Cellular Protein Quality Control System Modulates Cardiomyocyte Function in Volume Overload-Induced Hypertrophy |
| title_full | Altered Cellular Protein Quality Control System Modulates Cardiomyocyte Function in Volume Overload-Induced Hypertrophy |
| title_fullStr | Altered Cellular Protein Quality Control System Modulates Cardiomyocyte Function in Volume Overload-Induced Hypertrophy |
| title_full_unstemmed | Altered Cellular Protein Quality Control System Modulates Cardiomyocyte Function in Volume Overload-Induced Hypertrophy |
| title_short | Altered Cellular Protein Quality Control System Modulates Cardiomyocyte Function in Volume Overload-Induced Hypertrophy |
| title_sort | altered cellular protein quality control system modulates cardiomyocyte function in volume overload induced hypertrophy |
| topic | volume overload hypertrophy oxidative stress heat shock proteins protein quality control |
| url | https://www.mdpi.com/2076-3921/11/11/2210 |
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