Mechanisms of cell death.
Two distinct morphological patterns of cell death have been recognized, termed necrosis and apoptosis. Apoptosis, or programmed cell death, occurs in both physiological and pathological conditions. It arises due to an elevation of cytosolic free calcium concentration resulting in activation of a nuclear endonuclease. Activated endonuclease produces oligonucleosome-length DNA fragments. This DNA cleavage can directly precipitate cell death. Both glucocorticoids and TCDD may induce apoptosis by production of a heat labile factor that mediates calcium influx whereas tributyltin causes the opening of calcium channels. Evidence that perturbation in calcium homeostasis is an important event in cell necrosis is becoming increasingly persuasive, but the events that propagate the lesion are still unclear. Despite evidence for cytoskeletal disruption, activation of degradative enzymes such as proteases and phospholipase A2 and stimulation of other enzymes such as poly (ADP-ribose) polymerase, the exact role that these play in cell killing is not resolved. Indeed, recently the radical dichotomy between apoptosis and necrotic cell death has come into question. It is clear that further work is required to determine the role played by some elements of the apoptotic process in chemically induced cell death.
Fawthrop
D J
DJ
Department of Clinical Pharmacology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Boobis
A R
AR
Davies
D S
DS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D009243:NAD / Q000378:metabolism; D009336:Necrosis
D009243:NAD; D000255:Adenosine Triphosphate; D004247:DNA; D002118:Calcium