Early stages of p53-induced apoptosis are reversible.
Apoptosis is a type of physiological cell death that occurs during development, normal tissue homeostasis, or as a result of different cellular insults. The phenotype of an apoptotic cell is relatively consistent in most cases of apoptosis and involves at least changes in the cell membrane, proteolysis of cytoplasmic and nuclear proteins, and eventual destruction of nuclear DNA. Our laboratory is interested in the reversibility of apoptosis. We have initial evidence that DNA repair is activated early in p53-induced apoptosis and may be involved in its reversibility. The present work further strengthens our proposition that p53-induced apoptosis is reversible. We show that p53 activation induces phosphatidylserine (PS) externalization early in apoptosis, and that these early apoptotic cells with externalized PS can be rescued and proliferate if the apoptotic stimulus is removed. In addition, we show that unscheduled DNA synthesis occurs in early apoptotic cells, and that if DNA repair is inhibited by aphidicolin, apoptosis is accelerated. These results confirm that early p53-induced apoptotic cells can be rescued from the apoptotic program, and that DNA repair can modulate that cell death process.
Geske
F J
FJ
Department of Pathology, University of Colorado Health Sciences Center, Denver 80262, USA.
Lieberman
R
R
Strange
R
R
Gerschenson
L E
LE
D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D051379:Mice; D010718:Phosphatidylserines / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D010718:Phosphatidylserines; D016159:Tumor Suppressor Protein p53; D016590:Aphidicolin