Toward an understanding of the molecular mechanisms of physiological cell death.

Abstract

Cell death is a normal physiological process. Morphological studies have shown that cells that die by physiological mechanisms often undergo characteristic changes termed "apoptosis" or "programmed cell death." Recent work has begun to unravel the molecular mechanisms of these deaths and has shown that one of the primary cell-death pathways is conserved throughout much of evolution. In the nematode Caenorhabditis elegans programmed cell deaths are mediated by a mechanism controlled by the ced-9 gene; in mammals apoptosis can often be inhibited by expression of the bcl-2 gene. The ability of the human BCL2 gene to prevent cell deaths in C. elegans strongly suggests that bcl-2 and ced-9 are homologous genes. Although the process of cell death controlled by bcl-2 can occur in many cell types, there appears to be more than one physiological cell-death mechanism. Targets of cytotoxic T cells and cells deprived of growth factor both exhibit changes characteristic of apoptosis, such as DNA degradation. However, bcl-2 expression protects cells from factor withdrawal but fails to prevent cytotoxic T-cell killing. DNA degradation is, thus, not specific for any one cell-death mechanism. The ability of bcl-2 to protect cells from a wide variety of pathological, as well as physiological, stimuli indicates that many triggers can serve to activate the same suicide pathway, even some thought to cause necrosis, and not physiological cell death.

The pathophysiology of photosensitivity in lupus erythematosus

“…Apoptosis is an ordered means of non-inflammatory cell removal in which a central biochemical program initiates the dismantling of cells by nuclear fragmentation, formation of an apoptotic envelope and shrinking of the cell into fragments leading to phagocytosis by parenchymal cells as well as phagocytes (74)(75)(76). Apoptosis can be further categorized into ''immediate'' apoptosis or preprogrammed cell death, and ''intermediate'' and ''delayed'' apoptosis or programmed cell death (reviewed by (77)).…”

Tansley Review No. 118

“…During senescence, N stored in mature leaves is remobilized for transport to younger or more demanding plant parts. Hence the observation of increased protease activity, increased content of the readily transportable amino acids asparagine and glutamine, and appearance of ammonia in senescent tissues (Thomas, 1978 ;Vaux, 1993 ;BuchananWollaston, 1997 ;Distefano et al, 1997 ;Jiang et al, 1999). The cells around the vascular tissues are the last to senesce (Gan & Amasino, 1997), and this might be related to the requirement for prolonged transport ability.…”

“…Cell death in plants is a valuable mechanism for the survival of the whole organism, just as unchecked cell proliferation in animals is prevented by apoptosis (Vaux, 1993). Whereas apoptosis in mammals is now a well understood phenomenon, it is less so in plants, mainly because there are various forms of cell death, for example, programmed cell death in organogenesis, necrosis and senescence (Beers, 1997 ;Pennell & Lamb, 1997 ;Buckner et al, 1998).…”

“…expression (Godiard et al, 1998) and increased protease activity (Minami & Fukuda, 1995 ;Drake et al, 1996 ;Ye & Varner, 1996 ;Beers & Freeman, 1997 ;Gan & Amasino, 1997). In animals, the caspase subfamily of the cysteine proteases plays a key role in apoptotic cascade signalling, together with the appropriate regulatory signals (Vaux, 1993 ;Noode! n et al, 1997).…”

Autonomous proliferation and bcl-2 expression involving haematopoietic cells in patients with myelodysplastic syndrome

“…bcl-2 was initially detected at a translocation breakpoint in B-cell follicular lymphomas and was subsequently shown to have a role in preventing apoptosis (Korsmeyer. 1992: Vaux. 1993).…”