caa a22 4500 477120687 CHVBK 20180405111636.0 cr unu---uuuuu 170330e19960301xx s 000 0 eng 10.1007/BF00408667 doi (NATIONALLICENCE)springer-10.1007/BF00408667 Apoptosis in the heart: when and why? [Elektronische Daten] [Hans Jürgen Brömme, Jürgen Holtz] Since mammalian cardiac myocytes essentially rely on aerobic energy metabolism, it has been assumed that cardiocytes die in a catastrophic breakdown of cellular homeostasis (i.e. necrosis), if oxygen supply remains below a critical limit. Recent observations, however, indicate that a process of gene-directed cellular suicide (i.e. apoptosis) is activated in terminally differentiated cardiocytes of the adult mammalian heart by ischemia and reperfusion, and by cardiac overload as well. Apoptosis or programmed cell death is an actively regulated process of cellular self destruction, which requires energy and de novo gene expression, and which is directed by an inborn genetic program. The final result of this program is the fragmentation of nuclear DNA into typical "nucleosomal ladders”, while the functional integrity of the cell membrane and of other cellular organelles is still maintained. The critical step in this regulated apoptotic DNA fragmentation is the proteolytic inactivation of poly-[ADPribose]-polymerase (PARP) by a group of cysteine proteases with some structural homologies to interleukin-1β-converting enzyme (ICE-related proteases [IRPs] such as apopain, yama and others). PARP catalyzes the ADP-ribosylation of nuclear proteins at the sites of spontaneous DNA strand breaks and thereby facilitates the repair of this DNA damage. IRP-mediated destruction of PARP, the ‘supervisor of the genome', can be induced by activation of membrane receptors (e.g. FAS or APOI) and other signals, and is inhibited by activation of ‘anti-death genes' (e.g. bcl-2). Overload-triggered myocyte apoptosis appears to contribute to the transition to cardiac failure, which can be prevented by therapeutic hemodynamic unloading. In myocardial ischemia, the activation of the apoptotic program in cardiocytes does not exclude their final destiny to catastrophic necrosis with release of cytosolic enzymes, but might be considered as an adaptive process in hypoperfused ventricular zones, sacrificing some jeopardized myocytes to regulated apoptosis, which may by less arrhythmogenic than necrosis with the primary disturbance of membrane function. Kluwer Academic Publishers, 1996 apoptosis nationallicence necrosis nationallicence myocyte nationallicence heart nationallicence Jürgen Brömme Hans Institute of Pathophysiology, Martin Luther University Halle-Wittenberg, Magdeburger Str. 18, D-06097, Halle, Germany aut Holtz Jürgen Institute of Pathophysiology, Martin Luther University Halle-Wittenberg, Magdeburger Str. 18, D-06097, Halle, Germany aut Molecular and Cellular Biochemistry Kluwer Academic Publishers; http://www.wkap.nl 163-164/1(1996-03-01), 261-275 0300-8177 163-164:1<261 1996 163-164 11010 https://doi.org/10.1007/BF00408667 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00408667 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jürgen Brömme Hans Institute of Pathophysiology, Martin Luther University Halle-Wittenberg, Magdeburger Str. 18, D-06097, Halle, Germany aut NATIONALLICENCE 700 1- Holtz Jürgen Institute of Pathophysiology, Martin Luther University Halle-Wittenberg, Magdeburger Str. 18, D-06097, Halle, Germany aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Kluwer Academic Publishers; http://www.wkap.nl 163-164/1(1996-03-01), 261-275 0300-8177 163-164:1<261 1996 163-164 11010 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer