Apoptosis and toxicology--what relevance?
All cells are mortal-i.e. they can be killed if a vital metabolic process is blocked. All cells can engage in a variety of stress responses, such as the heat shock response, when vital processes are slowly, or only partially, inhibited. These stress responses involve detection of the damage, transduction of signals, and activation of a response, such as production of heat shock proteins, proteases, or chaperones. Many cells possess mechanisms whose purpose is to kill the cell. Such physiological cell death mechanisms are used to remove unwanted or damaged cells. Among metazoans, physiological cell death is implemented by a family of cysteine proteases, termed caspases, that exist in a latent state even in healthy cells. Cells killing themselves via activation of their caspases typically exhibit an appearance termed 'apoptosis'. Apoptosis is not only used to remove cells in physiological circumstances, such as during development, but is also a common response to cell stress. Thus many cells will detect damage to, or malfunctioning of, vital metabolic processes, and generate signals that lead to activation of the caspases, and apoptotic death of the cell. This has led to a great deal of confusion, because many drugs and toxins with known biochemical functions have been found to induce apoptosis, and rather than this being interpreted as a stress response, it has often wrongly been assumed that apoptosis is a direct effect of the drug or toxin.
Vaux
D L
DL
The Walter and Eliza Hall Institute of Medical Research, Royal Parade, Parkville, Vic 3050, Australia. vaux@wehi.edu.au
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D013312:Stress, Physiological / Q000473:pathology; D014116:Toxicology / Q000639:trends*