Activation of physiological cell death mechanisms by a necrosis-causing agent.
Cell death is an important physiological process, but it can be triggered by both physiological and nonphysiological stimuli. The product of the bcl-2 gene has the ability to inhibit a physiological cell death process that can be activated by a variety of physiological signals, such as growth factor deprivation. This report describes the use of electron microscopy to examine the effects of two cytotoxic drugs on factor-dependent cells that constitutively express the human bcl-2 gene. Although all cells treated with sodium azide showed changes typical of necrosis, in the absence of Bcl-2 the cells died more rapidly and also displayed features of apoptosis. The fact that Bcl-2 could delay cell death argues that cells can activate internal cell death mechanisms to commit suicide before they are killed by a cytotoxin. Northern analysis showed that growth factor did not preserve viability of the cells through induction of bcl-2. However, growth factor may prevent activation of the physiological cell death mechanisms that bcl-2 can control. This process may constitute a primitive defense response, and blocking it may provide a means of limiting damage caused by otherwise sublethal injuries.
Vaux
D L
DL
Department of Pathology, Stanford University Medical Center, California 94305, USA.
Whitney
D
D
Weissman
I L
IL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001386:Azides / Q000494:pharmacology*; D015152:Blotting, Northern; D001853:Bone Marrow / Q000378:metabolism / Q000648:ultrastructure; D001854:Bone Marrow Cells; D002453:Cell Cycle; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008854:Microscopy, Electron; D009153:Mutagens / Q000494:pharmacology*; D009336:Necrosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D019810:Sodium Azide
D001386:Azides; D009153:Mutagens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019810:Sodium Azide; D003078:Colchicine