Activation of physiological cell death mechanisms by a necrosis-causing agent.
Vaux DL., Whitney D., Weissman IL.
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.