Pyrrolidine dithiocarbamate inhibits serum-induced NF-kappa B activation and induces apoptosis in ROS 17/2.8 osteoblasts

Citation
H. Chae et al., Pyrrolidine dithiocarbamate inhibits serum-induced NF-kappa B activation and induces apoptosis in ROS 17/2.8 osteoblasts, INT IMMUNO, 1(2), 2001, pp. 255-263
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
INTERNATIONAL IMMUNOPHARMACOLOGY
ISSN journal
1567-5769 → ACNP
Volume
1
Issue
2
Year of publication
2001
Pages
255 - 263
Database
ISI
SICI code
1567-5769(200102)1:2<255:PDISNB>2.0.ZU;2-F
Abstract
Nuclear factor-kappaB (NF-kappaB) activity affects cell survival in ROS 17/ 2.8 osteoblasts. Preventing NF-kappaB transcription activity with a potent NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), results in apoptos is. Thus, we explored the effect of pyrrolidine dithiocarbamate (PDTC), whi ch potently blocks the activation of nuclear factor-kappaB (NF-kappaB) in s erum-exposed condition, on the activation of mitogen activated protein kina se (MAPK), especially, JNK/SAPK and p38 MAPK induction. PDTC transiently in creased the phosphotransferase activity of c-Jun N-terminal Kinase1 (JNK1), which might in turn activates transcriptional activity of activating prote in-1 (AP-1). The activation of JNK was completely decreased in dominant neg ative JNK1 transfected cells and the PDTC-induced cell death was attenuated in these cells. In addition, AP-1 activation was decreased in the JNK 1 tr ansfected cells, compared with vector-transfected cells. The NF-KB inhibito r also transiently activates p38 MAPK but SB203580, a specific p38 MAPK inh ibitor, does not have any regulatory effect on PDTC-induced cell death, sug gesting that the cell death is mediated by JNK not by p38 MAPK. Thus, overa ll, these results show that PDTC induces apoptosis and suggest that JNK/SAP K and subsequent AP-1 activation may be involved in the apoptotic pathway i n ROS 17/2.8 osteoblasts. (C) 2001 Elsevier Science B.V. All rights reserve d.