期刊
PHARMACOLOGICAL RESEARCH
卷 42, 期 4, 页码 373-381出版社
ACADEMIC PRESS LTD
DOI: 10.1006/phrs.2000.0700
关键词
staurosporine; osteoblast; apoptosis; caspase; transcriptional factor
.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. (C) 2000 Academic Press.
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