Molecular mechanism of staurosporine-induced apoptosis in osteoblasts.
Staurosporine, a microbial alkaloid, is a strong inhibitor of protein kinases. We induced apoptosis in murine osteoblast MC3T3E-1 cells by exposure to the staurosporine. Staurosporine transiently increased the phosphotransferase activity of c-Jun N-terminal kinase-1 (JNK1), which in turn may activate the transcriptional activity of activating protein-1 (AP-1). We then prepared extracts from staurosporine-treated MC3T3E-1 cells and monitored the cleavage of acetyl-YVAD-AMC and acetyl-DEVD-AMC, fluorogenic substrates of caspase-1-like and caspase-3-like proteases, respectively. Staurosporine caused a significant increase in the proteolytic activity of caspase-3-like proteases, but not in the activity of caspase-1-like proteases. Furthermore, staurosporine increased the transcriptional activity of nuclear factor- kappa B (NF- kappa B). These data suggest that staurosporine-induced apoptosis in osteoblasts may occur via activation of JNK1, caspase-3-like proteases, and transcriptional factors including AP-1 and NF- kappa B.
Chae
H J
HJ
Department of Dental Pharmacology and Wonkwang Dental Research Institute, Iksan, Chonbuk, Japan.
Kang
J S
JS
Byun
J O
JO
Han
K S
KS
Kim
D U
DU
Oh
S M
SM
Kim
H M
HM
Chae
S W
SW
Kim
H R
HR
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000737:chemistry; D010450:Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010770:Phosphotransferases / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D004791:Enzyme Inhibitors; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D010770:Phosphotransferases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D010450:Endopeptidases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine