title: Involvement of both caspase-like proteases and serine proteases in apoptotic cell death induced by ricin, modeccin, diphtheria toxin, and pseudomonas toxin.
abstract: We investigated the involvement of caspases and serine proteases in apoptotic cell death induced by ricin, modeccin, diphtheria toxin, and Pseudomonas toxin in U937 cells. We found that caspase-3- and caspase-6-like activities, but not caspase-1-like activity, increased during toxin-induced apoptosis. Z-D-CH2-DCB, a caspase-like inhibitor, completely inhibited the generation of caspase-3- and caspase-6-like activities and blocked all features of apoptosis induced by toxins: nuclear morphological changes, DNA fragmentation, and cytotoxicity. However, three caspase-specific inhibitors, Ac-YVAD-CHO, Ac-DEVD-CHO, and Ac-VEID-CHO, had no effect, even though Ac-DEVD-CHO and Ac-VEID-CHO inhibited the increased caspase-3- and caspase-6-like activity, respectively. These results suggest that the generation of caspase-3- and caspase-6-like activities is redundant, and other caspases distinct from caspase-3 and -6 may be important in toxin-induced apoptosis. Furthermore, serine protease inhibitor, 3,4-dichloroisocoumarine (DCI), abolished the apoptotic cell death and DNA fragmentation caused by toxins, without affecting the increased caspase-3- and caspase-6-like activities. Our results suggest that multiple proteases with different preferences for apoptotic substrates participate in toxin-induced apoptotic death of U937 cells.
authors.affiliation: Division of Biochemistry, Faculty of Fisheries, Nagasaki University, Bunkyo-machi, Nagasaki, 852-8521, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Komatsu
authors.forename: T
authors.initials: T
authors.lastname: Oda
authors.forename: T
authors.initials: T
authors.lastname: Muramatsu
mesh_terms: D036002:ADP Ribose Transferases; D017209:Apoptosis / Q000187:drug effects*; D001427:Bacterial Toxins; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004167:Diphtheria Toxin / Q000494:pharmacology*; D005098:Exotoxins / Q000494:pharmacology*; D006801:Humans; D037102:Lectins / Q000494:pharmacology*; D037121:Plant Lectins; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism*; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D003546:Cysteine Endopeptidases; D004167:Diphtheria Toxin; D005098:Exotoxins; D037102:Lectins; D037121:Plant Lectins; D011500:Protein Synthesis Inhibitors; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin; D012697:Serine Endopeptidases; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C016004:modeccin