Apoptosis: an overview

Abstract

The term apoptosis first appeared in the biomedical literature in 19721. That cells die had never been in doubt, and that some deaths are part of the enactment of a developmental programme had been recognised at least since the descriptive work of Glucksmann in 19512 and put on a firm experimental basis by Saunders3. The unique character of this developmentally regulated death had been encapsulated by the term programmed cell death, introduced by Lockshin4. The justification for the new term apoptosis was the realisation that cells entering death in development undergo a unique and distinct set of structural changes and that similar or identical changes are also shared by cells dying in a wide variety of circumstances outside of development: T-cell killing, negative selection within the immune system, atrophy induced by endocrine and other essentially physiological stimuli, normal cell turnover in many tissues, and in tumours and normal tissues following exposure to the appropriate (low) doses of ionising radiation, chemotherapy, and even hypoxia. Moreover, this process of death was clearly different from necrosis, till then the only mode of death that had been well described in pathological and toxicological literature, and which appears to be the consequence of extreme perturbations of the cellular microenvironment. Apoptosis represents a stereotyped sequence of structural change Briefly, the structural features of apoptosis include the following. The dying cell separates from its neighbours, usually with loss of specialised Corroipondancefo- membrane structures such as microvilli and desmosomes. It undergoes a Prof Andre wH Wyllm, period of blebbing and contortion that is dramatically visualised in time-