PDTC Inhibits TNF-alpha-Induced Apoptosis in MC3T3E1 Cells.
- Author:
Han Jung CHAE
1
;
Jeehyeon BAE
;
Soo Wan CHAE
Author Information
1. Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Jonju, Jeonbuk, South Korea. soowan@moak.chonbuk.ac.kr
- Publication Type:Original Article
- Keywords:
TNF-alpha;
Pyrrolidine dithiocarbamate;
NF-kappaB;
Osteoblasts;
Apoptosis;
c-Jun N-terminal kinase
- MeSH:
Apoptosis*;
Arthritis, Rheumatoid;
Bone Resorption;
Caspase 3;
Cytochromes c;
Inflammation;
JNK Mitogen-Activated Protein Kinases;
NF-kappa B;
Osteoblasts;
Periodontal Diseases;
Transcription Factor AP-1;
Transcription Factors;
Tumor Necrosis Factor-alpha
- From:The Korean Journal of Physiology and Pharmacology
2003;7(4):199-206
- CountryRepublic of Korea
- Language:English
-
Abstract:
Osteoblasts are affected by TNF-alpha overproduction by immune cells during inflammation. It has been suggested that functional NF-kappaB sites are involved in TNF-alpha-induced bone resorption. Thus, we explored the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor (NF-kappaB), on the induction of TNF-alpha-induced activation of JNK/SAPK, AP-1, cytochrome c, caspase and apoptosis in MC3T3E1 osteoblasts. Pretreatment of the cells with PDTC blocked TNF-alpha-induced NF-kappaB activation. TNF-alpha-induced activation of AP-1, another nuclear transcription factor, was suppressed by PDTC. The activation of c-Jun N-terminal kinase, implicated in the regulation of AP-1, was also down regulated by PDTC. TNF-alpha-induced apoptosis, release of cytochrome c and subsequent activation of caspase-3 were abolished by PDTC. TNF-alpha-induced apoptosis was partially blocked by Ac-DEVD-CHO, a caspase-3 inhibitor, suggesting that caspase-3 is involved in TNF-alpha- mediated signaling through NF-kappaB in MC3T3E1 osteoblasts. Thus, these results demonstrate that PDTC, has an inhibitory effect on TNF-alpha-mediated activation of JNK/SAPK, AP-1, cytochrome c release and subsequent caspase-3, leading to the inhibition of apoptosis. Our study may contribute to the treatment of TNF-alpha-associated immune and inflammatory diseases such as rheumatoid arthritis and periodontal diseases.
