Apoptosis and oncotic
necrosis in neuronal and glial cells have been documented in many neurological diseases. Distinguishing between these two major types of cell death in different neurological diseases is needed in order to better reveal the injury mechanisms so as to open up opportunities for
therapy development. Accumulating evidence suggests apoptosis and oncosis epitomize the extreme ends of a broad spectrum of morphological and biochemical events.
Biochemical markers that can distinguish between the
calpain and
caspase dominated types of cell death would help in this process. In this study, three chemical agents,
maitotoxin (MTX),
staurosporine (STS) and thylenediaminetetraacetic
acid (
EDTA), were used to induce different types of cell death in PC12 neuronal-like cells. MTX-induced
necrosis, as determined by the increased levels of
calpain-specific cleaved fragments of
spectrin by
antibodies specific to the
calpain-cleaved 150 kDa alphaII-
spectrin breakdown product (SBDP150) and 145 kDa alphaII-
spectrin breakdown product (SBDP145). In this paradigm, there were no detectable SBDP150i and SBDP120 fragments as determined by
antibodies specific to the
caspase-cleaved specific fragments similar to those seen in the
EDTA-mediated apoptotic PC-12 cells. In contrast to the
calpain specific MTX
necrosis treatment and the
caspase EDTA apoptotic treatment is the STS treatment which induced both
proteases as shown by the increase in all the
SBDP fragments. Furthermore, compared to SBDP150, SBDP145 appears to be a more specific and sensitive
biomarker for
calpain activation. Taken together, our results suggested calpains and
caspases which dominate the two major types of cell death could be independently discriminated by specifically examining the multiple alphaII-
spectrin cleavage breakdown products.