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001-es BibID:BIBFORM098750
035-os BibID:(cikkazonosító)1776
Első szerző:Bódi Beáta (molekuláris biológus)
Cím:Long-Term PDE-5A Inhibition Improves Myofilament Function in Left and Right Ventricular Cardiomyocytes through Partially Different Mechanisms in Diabetic Rat Hearts / Bódi Beáta, Kovács Árpád, Gulyás Hajnalka, Mártha Lilla, Tóth Attila, Mátyás Csaba, Barta Bálint András, Oláh Attila, Merkely Béla, Radovits Tamás, Papp Zoltán
Dátum:2021
ISSN:2076-3921
Megjegyzések:Heart failure with preserved ejection fraction (HFpEF) and right ventricular (RV) dysfunction are frequent complications of diabetic cardiomyopathy. Here we aimed to characterize RV and left ventricular (LV) remodeling and its prevention by vardenafil (a long-acting phosphodiesterase5A (PDE-5A) inhibitor) administration in a diabetic HFpEF model. Zucker Diabetic Fatty (ZDF) and control, ZDF Lean (Lean) male rats received 10 mg/kg vardenafil (ZDF + Vard; Lean + Vard) per os, on a daily basis for a period of 25 weeks. In vitro force measurements, biochemical and histochemical assays were employed to assess cardiomyocyte function and signaling. Vardenafil treatment increased cyclic guanosine monophosphate (cGMP) levels and decreased 3-nitrotyrosine (3-NT) levels in the left and right ventricles of ZDF animals, but not in Lean animals. Cardiomyocyte passive tension (Fpassive) was higher in LV and RV cardiomyocytes of ZDF rats than in those receiving preventive vardenafil treatment. Levels of overall titin phosphorylation did not differ in the four experimental groups. Maximal Ca2+-activated force (Fmax) of LV and RV cardiomyocytes were preserved in ZDF animals. Ca2+-sensitivity of isometric force production (pCa50) was significantly higher in LV (but not in RV) cardiomyocytes of ZDF rats than in their counterparts in the Lean or Lean + Vard groups. In accordance, the phosphorylation levels of cardiac troponin I (cTnI) and myosin binding protein-C (cMyBP-C) were lower in LV (but not in RV) cardiomyocytes of ZDF animals than in their counterparts of the Lean or Lean + Vard groups. Vardenafil treatment normalized pCa50 values in LV cardiomyocytes, and it decreased pCa50 below control levels in RV cardiomyocytes in the ZDF + Vard group. Our data illustrate partially overlapping myofilament protein alterations for LV and RV cardiomyocytes in diabetic rat hearts upon long-term PDE-5A inhibition. While uniform patterns in cGMP, 3-NT and Fpassive levels predict identical effects of vardenafil therapy for the diastolic function in both ventricles, the uneven cTnI, cMyBP-C phosphorylation levels and pCa50 values implicate different responses for the systolic function.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
right ventricle
HFpEF
diabetic cardiomyopathy
cardiomyocyte passive tension
Ca2+ - sensitivity of force production
myofilament protein phosphorylation
vardenafil
phosphodiesterase-5A
Megjelenés:Antioxidants. - 10 : 11 (2021), p. 1-13. -
További szerzők:Kovács Árpád (1986-) (kardiológus) Gulyás Hajnalka Mártha Lilla Tóth Attila (1971-) (biológus) Mátyás Csaba Barta Bálint András Oláh Attila Merkely Béla (1965-) (orvos) Radovits Tamás Papp Zoltán (1965-) (kardiológus, élettanász)
Pályázati támogatás:GINOP-2.3.2-15-2016-00043
GINOP
TKP2020-IKA-04
Egyéb
TKP2020-NKA-04
Egyéb
2020-4.1.1-TKP2020
Egyéb
NVKP_16-1-2016-0017
Egyéb
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2.

001-es BibID:BIBFORM005633
Első szerző:Hertelendi Zita (orvos)
Cím:Oxidation of myofilament protein sulfhydryl groups reduces the contractile force and its Ca2+ sensitivity in human cardiomyocytes / Hertelendi, Z., Toth, A., Borbely, A., Galajda, Z., van der Velden, J., Stienen, G. J., Edes, I., Papp, Z.
Dátum:2008
ISSN:1557-7716 (Electronic)
Megjegyzések:This study sought to characterize the relation between the oxidation of protein sulfhydryl (SH) groups and Ca2+-activated force production in the human myocardium. Triton-permeabilized left ventricular cardiomyocytes from donor hearts were exposed to an oxidative (2,2'-dithiodipyridine, DTDP) agent in vitro, and the changes in isometric force, its Ca2+ sensitivity, the cross-bridge-sensitive rate constant of force redevelopment at saturating [Ca2+] (k(tr,max)), and protein SH oxidation were monitored. DTDP (0.1-10 mM for 2 min) oxidized the myocardial proteins and diminished the Ca2+-activated force with different concentration dependences (EC(50,SH) = 0.17 +/- 0.02 mM and EC(50,force) = 2.46 +/- 0.22 mM; mean +/- SEM). The application of 2.5 mM DTDP decreased the maximal Ca2+-activated force (to 64%), its Ca2+ sensitivity (DeltapCa(50) = 0.22 +/- 0.02), and the steepness of the Ca2+-force relation (n(Hill), from 2.01 +/- 0.08 to 1.76 +/- 0.08). These changes were paralleled by reductions in the free SH content of the proteins (to 15%) and in k(tr,max) (to 75%). SH-specific labeling identified SH oxidation of myosin light chain 1 and actin at DTDP concentrations at which the changes in the contractile parameters occurred. Our data suggest that SH oxidation in selected myofilament proteins diminishes the Ca2+-activated force and its Ca2+ sensitivity through an impaired Ca2+ regulation of the actin-myosin cycle in the human heart.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
2,2'-Dipyridyl
Adult
Blotting, Western
Calcium
Cell Shape
Cells, Cultured
Disulfides
Female
Humans
Immunoprecipitation
Male
Microfilaments
Middle Aged
Myocardial Contraction
Myocytes, Cardiac
Oxidation-Reduction
Proteins/chemistry
Sulfhydryl Compounds
Megjelenés:Antioxidants and Redox Signaling. - 10 : 7 (2008), p. 1175-1184. -
További szerzők:Tóth Attila (1971-) (biológus) Borbély Attila (1978-) (kardiológus) Galajda Zoltán (1962-) (szívsebész, érsebész) Velden, Jolanda, van der Stienen, Ger J. M. Édes István (1952-) (kardiológus) Papp Zoltán (1965-) (kardiológus, élettanász)
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elektronikus változat
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3.

001-es BibID:BIBFORM095255
Első szerző:Kovács Árpád (kardiológus)
Cím:Interventricular Differences of Signaling Pathways-Mediated Regulation of Cardiomyocyte Function in Response to High Oxidative Stress in the Post-Ischemic Failing Rat Heart / Árpád Kovács, Melissa Herwig, Heidi Budde, Simin Delalat, Detmar Kolijn, Beáta Bódi, Roua Hassoun, Melina Tangos, Saltanat Zhazykbayeva, Ágnes Balogh, Dániel Czuriga, Sophie Van Linthout, Carsten Tschöpe, Naranjan S. Dhalla, Andreas Mügge, Attila Tóth, Zoltán Papp, Judit Barta, Nazha Hamdani
Dátum:2021
ISSN:2076-3921
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Antioxidants. - 10 : 6 (2021), p. 1-21. -
További szerzők:Herwig, Melissa Budde, Heidi Delalat, Simin Kolijn, Detmar Bódi Beáta (1989-) (molekuláris biológus) Hassoun, Roua Tangos, Melina Zhazykbayeva, Saltanat Balogh Ágnes (1984-) (kardiológus) Czuriga Dániel (1982-) (kardiológus) Linthout, Sophie Van Tschöpe, Carsten Dhalla, Naranjan S. Mügge, Andreas Tóth Attila (1971-) (biológus) Papp Zoltán (1965-) (kardiológus, élettanász) Barta Judit (1975-) (kardiológus) Hamdani, Nazha
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DOI
Intézményi repozitóriumban (DEA) tárolt változat
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