CASPASE INHIBITION PREVENTS STAUROSPORINE-INDUCED APOPTOSIS IN CHO-K1CELLS

Apoptosis is a distinct form of programmed cell death that plays an im portant role in many biological processes. Although the phenotypes of apoptotic cells are well documented, little is known of the central me chanism leading to programmed cell death. Over the past few years, a n umber of ICE/CED-3 family proteases (also termed caspases) have been d iscovered and implicated as the common effectors of apoptosis. In this report, we demonstrate that induction of apoptosis in CHO-K1 cells by staurosporine, a broad spectrum inhibitor of protein kinases, results in an increase in DEVD-dependent protease activity. These events were followed by nuclear DNA fragmentation and cell death. Inhibition of t he DEVD-cleaving activity by a synthetic tetrapeptide inhibitor DEVD-C HO, blocked staurosporine-induced downstream apoptotic phenotypes, suc h as morphological characteristics and DNA fragmentation. These result s suggest that staurosporine-induced apoptosis in CHO-K1 cells is medi ated through the CPP32/caspase-3-like cysteine proteases.