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Pyrrolidine dithiocarbamate inhibits serum-induced NF-kappaB activation and induces apoptosis in ROS 17/2.8 osteoblasts.
Int Immunopharmacol. 2001 Feb; 1(2):255-63.II

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 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.

Authors+Show Affiliations

Department of Dental Pharmacology, School of Dentistry, Wonkwang University, Iksan, Chonbuk, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11360927

Citation

Chae, H, et al. "Pyrrolidine Dithiocarbamate Inhibits Serum-induced NF-kappaB Activation and Induces Apoptosis in ROS 17/2.8 Osteoblasts." International Immunopharmacology, vol. 1, no. 2, 2001, pp. 255-63.
Chae H, Chae S, Park N, et al. Pyrrolidine dithiocarbamate inhibits serum-induced NF-kappaB activation and induces apoptosis in ROS 17/2.8 osteoblasts. Int Immunopharmacol. 2001;1(2):255-63.
Chae, H., Chae, S., Park, N., Bang, B., Cho, S., Kim, J., Kim, H., Kim, H., Lee, Z., & Kim, H. (2001). Pyrrolidine dithiocarbamate inhibits serum-induced NF-kappaB activation and induces apoptosis in ROS 17/2.8 osteoblasts. International Immunopharmacology, 1(2), 255-63.
Chae H, et al. Pyrrolidine Dithiocarbamate Inhibits Serum-induced NF-kappaB Activation and Induces Apoptosis in ROS 17/2.8 Osteoblasts. Int Immunopharmacol. 2001;1(2):255-63. PubMed PMID: 11360927.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pyrrolidine dithiocarbamate inhibits serum-induced NF-kappaB activation and induces apoptosis in ROS 17/2.8 osteoblasts. AU - Chae,H, AU - Chae,S, AU - Park,N, AU - Bang,B, AU - Cho,S, AU - Kim,J, AU - Kim,H, AU - Kim,H, AU - Lee,Z, AU - Kim,H, PY - 2001/5/22/pubmed PY - 2001/9/14/medline PY - 2001/5/22/entrez SP - 255 EP - 63 JF - International immunopharmacology JO - Int Immunopharmacol VL - 1 IS - 2 N2 - 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. SN - 1567-5769 UR - https://www.unboundmedicine.com/medline/citation/11360927/Pyrrolidine_dithiocarbamate_inhibits_serum_induced_NF_kappaB_activation_and_induces_apoptosis_in_ROS_17/2_8_osteoblasts_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(00)00025-4 DB - PRIME DP - Unbound Medicine ER -