Mechanical unloading of the rat heart involves marked changes in the protein kinase-phosphatase balance.
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Mechanical unloading of the rat heart involves marked changes in the protein kinase-phosphatase balance. / Schwoerer, Alexander; Neuber, Christiane; Schmechel, Ariane; Melnychenko, Ivan; Mearini, Giulia; Boknik, Peter; Kirchhefer, Uwe; Schmitz, Wilhelm; Ehmke, Heimo; Eschenhagen, Thomas; El-Armouche, Ali.
in: J MOL CELL CARDIOL, Jahrgang 45, Nr. 6, 6, 2008, S. 846-852.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Mechanical unloading of the rat heart involves marked changes in the protein kinase-phosphatase balance.
AU - Schwoerer, Alexander
AU - Neuber, Christiane
AU - Schmechel, Ariane
AU - Melnychenko, Ivan
AU - Mearini, Giulia
AU - Boknik, Peter
AU - Kirchhefer, Uwe
AU - Schmitz, Wilhelm
AU - Ehmke, Heimo
AU - Eschenhagen, Thomas
AU - El-Armouche, Ali
PY - 2008
Y1 - 2008
N2 - Mechanical unloading of failing hearts by left ventricular (LV) assist devices is regularly used as a bridge to transplantation and may lead to symptomatic improvement. The latter has been associated with altered phosphorylation of cardiac regulatory proteins, but the underlying mechanisms remained unknown. Here, we tested whether cardiac unloading alters protein phosphorylation by affecting the corresponding kinase-phosphatase balance. Cardiac unloading and reduction in LV mass were induced by heterotopic heart transplantation in rats for two weeks (n=8). Native in situ hearts from the recipient animals were used as controls (n=8). The steady-state protein kinase A (PKA) and/or Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) phosphorylation levels of phospholamban (PLB, Ser(16) and Thr(17)) and troponin I (TnI, Ser(23/24)) were decreased by 40-60% in unloaded hearts. Consistently, in these hearts PKA activity was decreased by approximately 80% and the activity of protein phosphatase 1 and 2A was increased by 50% and 90%, respectively. In contrast, CaMKII activity was approximately 60% higher, which may serve as a partial compensation. These data indicate that unloading shifts the kinase-phosphatase balance towards net dephosphorylation of PLB and TnI. This shift may also contribute to the reduction in phosphorylation levels of cardiac phosphoproteins observed in diseased human hearts after LVAD.
AB - Mechanical unloading of failing hearts by left ventricular (LV) assist devices is regularly used as a bridge to transplantation and may lead to symptomatic improvement. The latter has been associated with altered phosphorylation of cardiac regulatory proteins, but the underlying mechanisms remained unknown. Here, we tested whether cardiac unloading alters protein phosphorylation by affecting the corresponding kinase-phosphatase balance. Cardiac unloading and reduction in LV mass were induced by heterotopic heart transplantation in rats for two weeks (n=8). Native in situ hearts from the recipient animals were used as controls (n=8). The steady-state protein kinase A (PKA) and/or Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) phosphorylation levels of phospholamban (PLB, Ser(16) and Thr(17)) and troponin I (TnI, Ser(23/24)) were decreased by 40-60% in unloaded hearts. Consistently, in these hearts PKA activity was decreased by approximately 80% and the activity of protein phosphatase 1 and 2A was increased by 50% and 90%, respectively. In contrast, CaMKII activity was approximately 60% higher, which may serve as a partial compensation. These data indicate that unloading shifts the kinase-phosphatase balance towards net dephosphorylation of PLB and TnI. This shift may also contribute to the reduction in phosphorylation levels of cardiac phosphoproteins observed in diseased human hearts after LVAD.
M3 - SCORING: Zeitschriftenaufsatz
VL - 45
SP - 846
EP - 852
JO - J MOL CELL CARDIOL
JF - J MOL CELL CARDIOL
SN - 0022-2828
IS - 6
M1 - 6
ER -
