ABSTRACT
Apoptosis Research Group, Institute for Biological Sciences, National Research Council of Canada, Ottawa ON, Canada K1A 0R6
An electrophoretic laddered pattern of DNA fragments remains the premiere biochemical hallmark of an apoptotic mode of cell death (Wyllie et al., 1980; Bortner et al., 1995; Walker and Sikorska, 1997). This electrophoretic laddered pattern arises from scission of the internucleosomal linker DNA in chromatin that results in oligomeric 200 base pair (bp) fragments; it has been documented in a wide variety of cells and tissues induced to die by innumerable insults. Neurons die by apoptosis in mammoth numbers during fetal and early postnatal development as supernumerary precursor neuroblasts are culled during synapse formation (Lo et al., 1995). The programmed cell death of such immature neurons is regarded as apoptotic since, for one, they exhibit the biochemical characteristic of laddered DNA fragmentation (Blaschke et al., 1996; PorteraCailliau et al., 1997a). Electrophoretic patterns of laddered DNA fragments have also been seen in ischemic brain tissue. But, one may ask, are all DNA-
ladders the same? The fragmentation following cerebral ischemia has been considered apoptotic for several reasons. First, the fragments appear as approximately 200 bp oligomers, which is similar to classic apoptosis (reviewed in Charriaut-Marlangue et al., 1996; Choi, 1996; MacManus and Linnik, 1997). Second, the fragmentation is different from the random cleavage of necrosis (Tominaga et al., 1993; MacManus et al., 1995). Third, there is evident involvement of the apoptotic protease, caspase-3, following cerebral ischemia (Endres et al., 1998; Namura et al., 1998) and a caspase-activated nuclear endonuclease has been recently described (Enari et al., 1998) that may be active in injured brain tissue.
