Calpain involvement in calphostin C-induced apoptosis.
A major problem in assessing the role of calpains in apoptosis induction concerns the fact that calpain inhibitors can also impair the activity of the proteasome, also reported to be involved in apoptosis. Herein we showed that apoptosis induced by calphostin C in U937 human promonocytic leukemia cells was associated, at its onset, with enhanced protein (poly)ubiquitination. This observation prompted us to study whether protein degradation through the ubiquitin/proteasome pathway was involved in apoptosis induction. We found that N-acetyl-Leu-Leu-norleucinal (50 microM), a proteasome as well as a calpain inhibitor, was able to reduce calphostin C-induced apoptosis by approximately 60%, whereas lactacystin (10 microM), a specific proteasome inhibitor, was ineffective. These results suggest that calphostin C-induced apoptosis is partly calpain-mediated, but does not require protein degradation through the ubiquitin/proteasome pathway.
Spinedi
A
A
Department of Biology, University of Rome Tor Vergata, Italy. spinedi@seneca.ccd.utovrm.it
Oliverio
S
S
Di Sano
F
F
Piacentini
M
M
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D020298:U937 Cells; D014452:Ubiquitins / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D009097:Multienzyme Complexes; D009281:Naphthalenes; D009363:Neoplasm Proteins; D014452:Ubiquitins; C063261:acetylleucyl-leucyl-norleucinal; C067713:lactacystin; D002154:Calpain; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C058819:calphostin C; D000111:Acetylcysteine