Distinct interleukin-1beta-converting enzyme family proteases mediate cisplatin- and staurosporine-induced apoptosis of mouse proximal tubule cells.
Interleukin-1beta converting enzyme (ICE) family proteases (caspases) are known to be implicated as important effectors of apoptotic pathways. The purpose of this study was to elucidate the role of ICE family proteases in apoptosis of mouse cells derived from the terminal proximal tubule (S3) treated with cisplatin, an anti-tumor drug, or staurosporine, a protein kinase C inhibitor. For this purpose, we measured the activities of ICE family proteases and examined the effects of tetrapeptide and viral ICE family protease inhibitors on the activities of ICE family proteases in and the degree of apoptosis of S3 cells treated with cisplatin and staurosporine. RT-PCR analysis revealed that S3 cells as well as mouse kidney express mRNA for ICE and CPP32, an ICE family protease. Results of enzymatic analysis, determination the degree of DNA fragmentation and cytotoxicity test suggest that CPP32 mediates cisplatin-induced apoptosis of S3 cells, whereas ICE family proteases other than CPP32 mediate staurosporine-induced apoptosis of S3 cells. In conclusion, distinct ICE family proteases mediate apoptosis of mouse proximal tubule cells depending on the stimuli to which the cells are exposed.
Fukuoka
K
K
The First Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Takeda
M
M
Kobayashi
M
M
Osaki
T
T
Shirato
I
I
Soejima
A
A
Nagasawa
T
T
Endou
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000633:toxicity*; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D015843:Serpins / Q000494:pharmacology; D019311:Staurosporine / Q000633:toxicity*; D014158:Transcription, Genetic; D014764:Viral Proteins
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D012333:RNA, Messenger; D015843:Serpins; D014764:Viral Proteins; C074641:interleukin-1beta-converting enzyme inhibitor; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D019311:Staurosporine; D002945:Cisplatin