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001-es BibID:	BIBFORM057836
Első szerző:	Kalász Judit (molekuláris biológus)
Cím:	Myeloperoxidase impairs the contractile function in isolated human cardiomyocytes / Judit Kalász, Enikő Pásztorné Tóth, Miklós Fagyas, Ágnes Balogh, Attila Tóth, Viktória Csató, István Édes, Zoltán Papp, Attila Borbély
Dátum:	2015
Megjegyzések:	Purpose: We set out to characterize the mechanical effects of myeloperoxidase (MPO) in isolated left ventricular human cardiomyocytes. Oxidative myofilament protein modifications (sulfhydryl (SH) group oxidation and carbonylation) induced by the peroxidase and chlorinating activities of MPO were additionally identified. The specificity of the MPOevoked functional alterations was tested with an MPO inhibitor (MPO-I) and the antioxidant amino acid Met.Results: The combined application of MPO and its substrate, hydrogen peroxide (H2O2),largely reduced the active force (Factive), increased the passive force (Fpassive) and decreasedthe Ca2+ sensitivity of force production (pCa50) in permeabilized cardiomyocytes. H2O2 alonehad significantly smaller effects on Factive and Fpassive and did not alter pCa50. The MPO-I blocked both the peroxidase and chlorinating activities, while Met selectively inhibited the chlorinating activity of MPO. All of the MPO-induced functional effects could be prevented by the MPO-I and Met. Both H2O2 alone and MPO+H2O2 reduced the SH content of actin and increased the carbonylation of actin and myosin-binding protein C to the same extent. Neither the SH-oxidation nor the carbonylation of the giant sarcomeric protein titin was affected by these treatments. Conclusions: MPO activation induces a cardiomyocyte dysfunction by affecting Ca2+-regulated active and Ca2+-independent passive force production and myofilament Ca2+ sensitivity, independently of protein SH oxidation and carbonylation. The MPO-induced deleterious functional alterations can be prevented by the MPO-I and Met. Inhibition of MPO may be a promising therapeutic target to limit myocardial contractile dysfunction during inflammation.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban kontraktilis funkció
Megjelenés:	Free Radical Biology & Medicine. - 84 (2015), p. 116-127. -
További szerzők:	Pásztorné Tóth Enikő (1966-) (laboratóriumi analitikus) Fagyas Miklós (1984-) (orvos) Balogh Ágnes (1984-) (kardiológus) Tóth Attila (1971-) (biológus) Csató Viktória (1986-) (molekuláris biológus) Édes István (1952-) (kardiológus) Papp Zoltán (1965-) (kardiológus, élettanász) Borbély Attila (1978-) (kardiológus)
Pályázati támogatás:	PD 108614 OTKA K 109083 OTKA 4.2.4. A/2-11-1-2012-0001 TÁMOP TÁMOP-4.2.2.A-11/1/KONV-2012-0045 TÁMOP Kardiológia Kutatócsoport FP7-Health-2010 Egyéb MEDIA-261409 Egyéb
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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