title: Akt1 expression and activity at different stages in experimental heart failure.
abstract: Loss of function or/and death of cardiomyocytes is one of the major contributing factors in the development of heart failure. Cytosolic Hsp60 can directly interact and regulate activation of some kinases and sequestrate certain proapoptotic molecules to avoid the cardiomyocyte apoptosis. We assumed that Akt1 kinase, a downstream effector of PI3 kinase, can interact with Hsp60. Our aim was to clarify the interaction of Akt1 and Hsp60 and to investigate the Akt1 expression in normal and failing hearts in acute and chronic stress. The experimental mouse models of inducible myocarditis and DCM-like pathology were developed in our laboratory. Akt1 and phospho-Akt1 (pS473) expression were studied by Western blot analysis. Co-immunoprecipitation method was used to test complex formation of Akt1 and Hsp60. The interaction of Hsp60 and Akt1 was detected for the first time by co-immunoprecipitation method in normal myocardium and under pathology as well. There were no significant changes in the level of Akt1 expression in both myocardia. At the same time we observed significant decrease in Akt1 phosphorylation at the final stage of DCM-like pathology but not at experimental myocarditis. The final stage of heart failure in mouse model of DCM-like pathology was characterized by reduced level of phospho-Akt1/Akt1 (pS473; -26%; P<0.05), whereas no differences were found in total Akt1 protein content. We suggest a possible involvement of cytoplasmic Hsp60 in regulation of Akt1 activity at heart failure progression.
authors: Institute of Molecular Biology and Genetics, NAS of Ukraine, 150, Zabolotnogo Str., Kyiv 03680, Ukraine. Electronic address: lyuda-kap@mail.ru.
authors: L
authors: L
authors: Kapustian
authors: Institute of Molecular Biology and Genetics, NAS of Ukraine, 150, Zabolotnogo Str., Kyiv 03680, Ukraine.
authors: I
authors: I
authors: Kroupskaya
authors: Institute of Molecular Biology and Genetics, NAS of Ukraine, 150, Zabolotnogo Str., Kyiv 03680, Ukraine.
authors: O
authors: O
authors: Rozhko
authors: Institute of Molecular Biology and Genetics, NAS of Ukraine, 150, Zabolotnogo Str., Kyiv 03680, Ukraine.
authors: V
authors: V
authors: Bobyk
authors: National Scientific Center "M. D. Strazhesko Institute of Cardiology, MAS of Ukraine", 5, Narodnogo Opolchenya Str., Kyiv 03151, Ukraine.
authors: D
authors: D
authors: Ryabenko
authors: Institute of Molecular Biology and Genetics, NAS of Ukraine, 150, Zabolotnogo Str., Kyiv 03680, Ukraine.
authors: L
authors: L
authors: Sidorik
keywords: Akt kinase; DCM; Heart failure; Hsp60; Mice; Myocarditis