| Research Abstract |
Glucocorticoid (GC) is used for the treatment of leukemias or lymphomas because GC induces apoptosis in certain types of lymphocytes. However, the mechanism of how GC mediates apoptosis is unknown. The purpose of this research project was to elucidate the molecular mechanism of GC-mediated apoptosis. During the period of two years we got the results as follows using 697, a pre-B leukemia cell line.
1. Reduction of mitochondrial membrane potential and reactive oxygen production were observed during GC-mediated apoptosis. Both of which, as well as cell death itself were inhibited by a pan-caspase inhibitor, zVAD-fmk.
2. On the other hand, a caspase-3-like protease inhibitor, AC-DEVD-CHO inhibited neither of them, while significantly inhibited DNA fragmentation.
3.These results indicate the presence of caspase(s), which is inhibited by zVAD-fmk but not by AC-DEVD-CHO, upstream of mitochondrial changes.
4.Unexpectedly, caspase-3, a main effector caspase, was not proteolytically activated during GC-induced apoptosis.
5. Instead, caspase-6 and -7, other effector caspases, were processed and activated.
6. These results indicate that apoptosis triggered by GC has a distinct pathway where caspase-3 is not involved.
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