CALPAIN INVOLVEMENT IN CALPHOSTIN C-INDUCED APOPTOSIS

A major problem in assessing the role of calpains in apoptosis inducti on concerns the fact that calpain inhibitors can also impair the activ ity of the proteasome, also reported to be involved in apoptosis. Here in we showed that apoptosis induced by calphostin C in U937 human prom onocytic leukemia cells was associated, at its onset, with enhanced pr otein (poly)ubiquitination. This observation prompted us to study whet her protein degradation through the ubiquitin/proteasome pathway was i nvolved in apoptosis induction. We found that N acetyl-Leu-Leu-norleuc inal (50 mu M), a proteasome as well as a calpain inhibitor, was able to reduce calphostin C-induced apoptosis by approximately 60%, whereas lactacystin (10 mu M), a specific proteasome inhibitor, was ineffecti ve. These results suggest that calphostin C-induced apoptosis is partl y calpain-mediated, but does not require protein degradation through t he ubiquitin/proteasome pathway. BIOCHEM PHARMACOL 56;11:1489-1492, 19 98. (C) 1998 Elsevier Science Inc.