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001-es BibID:BIBFORM109139
035-os BibID:(cikkazonosító)1134 (scopus)85110167526 (wos)000675938200001
Első szerző:Budde, Heidi
Cím:The Interplay between S-Glutathionylation and Phosphorylation of Cardiac Troponin I and Myosin Binding Protein C in End-Stage Human Failing Hearts / Budde Heidi, Hassoun Roua, Tangos Melina, Zhazykbayeva Saltanat, Herwig Melissa, Varatnitskaya Marharyta, Sieme Marcel, Delalat Simin, Sultana Innas, Kolijn Detmar, Gömöri Kamilla, Jarkas Muhammad, Lódi Mária, Jaquet Kornelia, Kovács Árpád, Mannherz Hans Georg, Sequeira Vasco, Mügge Andreas, Leichert Lars I., Sossalla Samuel, Hamdani Nazha
Dátum:2021
ISSN:2076-3921
Megjegyzések: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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Antioxidants. - 10 : 7 (2021), p. 1-26. -
További szerzők:Hassoun, Roua Tangos, Melina Zhazykbayeva, Saltanat Herwig, Melissa Varatnitskaya, Marharyta Sieme, Marcel Delalat, Simin Sultana, Innas Kolijn, Detmar Gömöri Kamilla Jarkas, Muhammad Lódi Mária (1991-) Jaquet, Kornelia Kovács Árpád (1986-) (kardiológus) Mannherz, Hans Georg Sequeira, Vasco Mügge, Andreas Leichert, Lars I. Sossalla, Samuel Hamdani, Nazha
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2.

001-es BibID:BIBFORM109142
035-os BibID:(scopus)85120642459 (wos)000729080200010
Első szerző:Hassoun, Roua
Cím:Do they come together? Protein quality control, stress-activated signaling, and "sarcostat" in hypertrophic cardiomyopathy progression / Hassoun Roua, Budde Heidi, Zhazykbayeva Saltanat, Herwig Melissa, Sieme Marcel, Delalat Simin, Mostafi Nusratul, Gömöri Kamilla, Tangos Melina, Jarkas Muhammad, Pabel Steffen, Bruckmüller Stefanie, Skrygan Marina, Lódi Mária, Jaquet Kornelia, Sequeira Vasco, Gambichler Thilo, Remedios Cris Dos, Kovács Árpád, Mannherz Hans Georg, Mügge Andreas, Sossalla Samuel, Hamdani Nazha
Dátum:2022
ISSN:0167-5273
Tárgyszavak:Orvostudományok Elméleti orvostudományok levél
folyóiratcikk
Megjelenés:International Journal Of Cardiology. - 347 (2022), p. 44-45. -
További szerzők:Budde, Heidi Zhazykbayeva, Saltanat Herwig, Melissa Sieme, Marcel Delalat, Simin Mostafi, Nusratul Gömöri Kamilla Tangos, Melina Jarkas, Muhammad Pabel, Steffen Bruckmüller, Stefanie Skrygan, Marina Lódi Mária (1991-) Jaquet, Kornelia Sequeira, Vasco Gambichler, Thilo Remedios, Cris Kovács Árpád (1986-) (kardiológus) Mannherz, Hans Georg Mügge, Andreas Sossalla, Samuel Hamdani, Nazha
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3.

001-es BibID:BIBFORM109140
035-os BibID:(scopus)85115118583 (wos)000757375800031
Első szerző:Hassoun, Roua
Cím:Stress activated signalling impaired protein quality control pathways in human hypertrophic cardiomyopathy / Hassoun Roua, Budde Heidi, Zhazykbayeva Saltanat, Herwig Melissa, Sieme Marcel, Delalat Simin, Mostafi Nusratul, Gömöri Kamilla, Tangos Melina, Jarkas Muhammad, Pabel Steffen, Bruckmüller Stefanie, Skrygan Marina, Lódi Mária, Jaquet Kornelia, Sequeira Vasco, Gambichler Thilo, Remedios Cris Dos, Kovács Árpád, Mannherz Hans Georg, Mügge Andreas, Sossalla Samuel, Hamdani Nazha
Dátum:2021
ISSN:0167-5273
Megjegyzések:Hypertrophic cardiomyopathy (HCM) is a complex myocardial disorder with no well-established disease-modifying therapy so far. Our study aimed to investigate how autophagy, oxidative stress, inflammation, stress signalling pathways, and apoptosis are hallmark of HCM and their contribution to the cardiac dysfunction. Demembranated cardiomyocytes from patients with HCM display increased titin-based stiffness (Fpassive), which was corrected upon antioxidant treatment. Titin as a main determinant of Fpassive was S-glutathionylated and highly ubiquitinated in HCM patients. This was associated with a shift in the balance of reduced and oxidized forms of glutathione (GSH and GSSG, respectively). Both heat shock proteins (HSP27 and ?-? crystalline) were upregulated and S-glutathionylated in HCM. Administration of HSPs in vitro significantly reduced HCM cardiomyocyte stiffness. High levels of the phosphorylated monomeric superoxide anion-generating endothelial nitric oxide synthase (eNOS), decreased nitric oxide (NO) bioavailability, decreased soluble guanylyl cyclase (sGC) activity, and high levels of 3-nitrotyrosine were observed in HCM. Many regulators of signal transduction pathways that are involved in autophagy, apoptosis, cardiac contractility, and growth including the mitogen-activated protein kinase (MAPK), protein kinase B (AKT), glycogen synthase kinase 3? (GSK-3?), mammalian target of rapamycin (mTOR), forkhead box O transcription factor (FOXO), c-Jun N-terminal protein kinase (JNK), and extracellular-signal-regulated kinase (ERK1/2) were modified in HCM. The apoptotic factors cathepsin, procaspase 3, procaspase 9 and caspase 12, but not caspase 9, were elevated in HCM hearts and associated with increased proinflammatory cytokines (Interleukin 6 (IL-6), interleukin 18 (IL-18), intercellular cell adhesion molecule-1 (ICAM1), vascular cell adhesion molecule-1 (VCAM1), the Toll-like receptors 2 (TLR2) and the Toll-like receptors 4 (TLR4)) and oxidative stress (3-nitrotyrosine and hydrogen peroxide (H2O2)). Here we reveal stress signalling and impaired PQS as potential mechanisms underlying the HCM phenotype. Our data suggest that reducing oxidative stress can be a viable therapeutic approach to attenuating the severity of cardiac dysfunction in heart failure and potentially in HCM and prevent its progression.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:International Journal Of Cardiology. - 344 (2021), p. 160-169. -
További szerzők:Budde, Heidi Zhazykbayeva, Saltanat Herwig, Melissa Sieme, Marcel Delalat, Simin Mostafi, Nusratul Gömöri Kamilla Tangos, Melina Jarkas, Muhammad Pabel, Steffen Bruckmüller, Stefanie Skrygan, Marina Lódi Mária (1991-) Jaquet, Kornelia Sequeira, Vasco Gambichler, Thilo Remedios, Cris Kovács Árpád (1986-) (kardiológus) Mannherz, Hans Georg Mügge, Andreas Sossalla, Samuel Hamdani, Nazha
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4.

001-es BibID:BIBFORM102227
035-os BibID:(WoS)000879481000020 (Scopus)85131795534
Első szerző:Tangos, Melina
Cím:SARS-CoV-2 infects human cardiac myocytes promoted by inflammation and oxidative stress / Tangos Melina, Budde Heidi, Kolijn Detmar, Sieme Marcel, Zhazykbayeva Saltanat, Lódi Mária, Herwig Melissa, Gömöri Kamilla, Hassoun Roua, Robinson Emma Louise, Meister Toni Luise, Jaquet Kornelia, Kovács Árpád, Mustroph Julian, Evert Katja, Babel Nina, Miklós Fagyas, Lindner Diana, Püschel Klaus, Westermann Dirk, Mannherz Hans Georg, Paneni Francesco, Pfaender Stephanie, Toth Attila, Mügge Andreas, Sossalla Samuel, Hamdani Nazha
Dátum:2022
ISSN:0167-5273
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:International Journal Of Cardiology. - 362 (2022), p. 196-205. -
További szerzők:Budde, Heidi Kolijn, Detmar Sieme, Marcel Zhazykbayeva, Saltanat Lódi Mária (1991-) Herwig, Melissa Gömöri Kamilla Hassoun, Roua Robinson, Emma Louise Meister, Toni Luise Jaquet, Kornelia Kovács Árpád (1986-) (kardiológus) Mustroph, Julian Evert, Katja Babel, Nina Fagyas Miklós (1984-) (orvos) Lindner, Diana Püschel, Klaus Westermann, Dirk Mannherz, Hans Georg Paneni, Francesco Pfaender, Stephanie Tóth Attila (1971-) (biológus) Mügge, Andreas Sossalla, Samuel Hamdani, Nazha
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