Pyrrolidine dithiocarbamate inhibits serum-induced NF-kappaB activation and induces apoptosis in ROS 17/2.8 osteoblasts.
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 apoptosis. Thus, we explored the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor-kappaB (NF-kappaB) in serum-exposed condition, on the activation of mitogen activated protein kinase (MAPK), especially, JNK/SAPK and p38 MAPK induction. PDTC transiently increased the phosphotransferase activity of c-Jun N-terminal Kinase1 (JNK1), which might in turn activates transcriptional activity of activating protein-1 (AP-1). The activation of JNK was completely decreased in dominant negative JNK1 transfected cells and the PDTC-induced cell death was attenuated in these cells. In addition, AP-1 activation was decreased in the JNK1 transfected cells, compared with vector-transfected cells. The NF-kappaB inhibitor also transiently activates p38 MAPK but SB203580, a specific p38 MAPK inhibitor, does not have any regulatory effect on PDTC-induced cell death, suggesting that the cell death is mediated by JNK not by p38 MAPK. Thus, overall, these results show that PDTC induces apoptosis and suggest that JNK/SAPK and subsequent AP-1 activation may be involved in the apoptotic pathway in ROS 17/2.8 osteoblasts.
Chae
H
H
Department of Dental Pharmacology, School of Dentistry, Wonkwang University, Iksan, Chonbuk, South Korea.
Chae
S
S
Park
N
N
Bang
B
B
Cho
S
S
Kim
J
J
Kim
H
H
Kim
H
H
Lee
Z
Z
Kim
H
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D013859:Thiocarbamates / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D018808:Transcription Factor AP-1; C020972:pyrrolidine dithiocarbamic acid; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases