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001-es BibID:	BIBFORM005628
Első szerző:	Édes István Ferenc (kardiológus)
Cím:	Late-stage alterations in myofibrillar contractile function in a transgenic mouse model of dilated cardiomyopathy (Tgalphaq*44) / Edes, I. F., Toth, A., Csanyi, G., Lomnicka, M., Chlopicki, S., Edes, I., Papp, Z.
Dátum:	2008
ISSN:	1095-8584 (Electronic)
Megjegyzések:	Mechanical and biochemical alterations were investigated in permeabilized cardiomyocytes along with the progression of dilated cardiomyopathy (DCM) in a transgenic mouse line overexpressing the activated Galphaq protein (Tgalphaq44). The isometric force, its Ca(2+) sensitivity (pCa(50)) and the turnover rate of the actin-myosin cycle (k(tr)) were determined at sarcomere lengths (SLs) of 1.9 mum and 2.3 mum before (at 4 and 10 months of age) and after hemodynamic decompensation (at 14 and 18 months of age) in Tgalphaq44 cardiomyocytes and in age-matched control cardiomyocytes. The SL-dependence of pCa(50) was not different in Tgalphaq44 and control hearts. In contrast, a significant increase in pCa(50) was observed in the Tgalphaq44 cardiomyocytes (DeltapCa(50): 0.10-0.15 vs. the controls) after 10 months of age that could be diminished by exposures to the catalytic subunit of protein kinase A (PKA). Accordingly, a decline in endogenous PKA activity and decreased troponin I phosphorylation were detected after 10 months in the Tgalphaq44 hearts. Finally, the maximal Ca(2+)-activated force (F(o)) and k(tr) were lower and the passive force (F(passive)) was higher at 18 months in the Tgalphaq44 cardiomyocytes compared to the control. These mechanical alterations were paralleled by a robust increase in beta-myosin heavy chain expression in the Tgalphaq44 hearts. In conclusion, our data suggested that an initial decrease of PKA signaling and subsequent changes in myofilament protein expression may contribute to the development of dilated cardiomyopathy in Tgalphaq44 hearts.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Animals Cardiomyopathy, Dilated Cattle Cells, Cultured Disease Models, Animal Female GTP-Binding Protein alpha Subunits Male Mice Mice, Transgenic Models, Cardiovascular Myocardial Contraction Myocytes, Cardiac Myofibrils
Megjelenés:	Journal of Molecular and Cellular Cardiology. - 45 : 3 (2008), p. 363-372. -
További szerzők:	Tóth Attila (1971-) (biológus) Csányi Gábor Lomnicka, Magdalena Chlopicki, Stefan Édes István (1952-) (kardiológus) Papp Zoltán (1965-) (kardiológus, élettanász)
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