ABSTRACT
Ireland KEY WORDS: caspase, caspase inhibitors-crmA, IAP, p35, zVAD-fmk, “commitment step”, cytotoxic drugs-actinomycin D, dexamethasone, etoposide, staurosporine, developmental death-C.elegans, Drosophila, mitochondria-AIF, cytochrome c, permeability transition (PT), ROS, oncogenes-Bax, Bcl, Bcr-Abl, c-myc
INTRODUCTION
It is now widely accepted that apoptosis, or active cell death, is essential for the development and cellular homeostasis of metazoan animals. The fundamental importance of this form of cell death can be appreciated by its conservation throughout evolution (Ameisen et al., 1995; Ameisen, 1996; Cornillon et al., 1994; Vaux et al., 1994). Apoptosis constitutes an intrinsic suicide mechanism that systematically destroys the cell with characteristic morphological and biochemical changes without initiating an inflammatory response (Kerr et al., 1972; Wyllie, 1980; Arends and Wyllie, 1991; Raff, 1992). This altruistic process is extremely rapid (minutes to hours) and the resulting apoptotic debris is cleared with similar efficiency. Perturbations in this process have been implicated in a range of human pathological disorders including cancer (Green et al., 1994; Thompson, 1995; Williams, 1991; Martin and Green, 1995), acquired immunodeficiency syndrome (AIDS) (Ameisen, 1994; Terai et al., 1991; Meyaard et al., 1992; Martin, 1993; Ameisen and Capron, 1991), ischemic injury (Martinou, 1994) and neurodegenerative disorders (Carson and Ribeiro, 1993; Loo et al., 1993; Holden and Mooney, 1995). Thus investigations into the regulation of apoptosis may have important therapeutic potential.
