Time course of the apoptotic cascade and effects of caspase inhibitors in adult rat ventricular cardiomyocytes

Journal of Molecular and Cellular Cardiology
K SuzukiJ Schaper

Abstract

K. Suzuki, S. Kostin, V. Person, A. Elsässer and J. Schaper. Time Course of the Apoptotic Cascade and Effects of Caspase Inhibitors in Adult Rat Ventricular Cardiomyocytes. Journal of Molecular and Cellular Cardiology (2001) 33, 983-994. Interpretation of the rate of apoptosis in diseased hearts is hampered by the fact that the time course of the apoptotic cascade in adult cardiomyocytes is largely unknown. Therefore, we established a standardized in vitro system, relevant to the in vivo situation of heart failure, using adult de- and redifferentiating cardiomyocytes to determine the time intervals necessary for the different steps of the apoptotic cascade to occur. Apoptosis was induced with 0.1 mmol/l H(2)O(2)in adult rat cardiomyocytes 10 days in culture. Dosages >0.5 mmol/l H(2)O(2)produced necrosis. Disruption of the mitochondrial membrane potential (Deltapsim) was the earliest sign of apoptosis and occurred at 2 h after H(2)O(2)exposure. The number of annexin V (translocation of phosphatidylserine) and PhiPhiLux (activation of caspase-3) positive cells significantly increased after 4 h and remained constant thereafter. Bcl-2 levels decreased. At 9 h, Bax expression was significantly elevated resulting in a reduced Bcl-2/B...Continue Reading

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