Prologation of c-Jun N-Terminal Kinase is Associated with Cell Death Induced by Tumor Necrosis Factor Alpha in Human Chondrocytes.
10.3346/jkms.2004.19.4.567
- Author:
Ho Sung YOON
1
;
Hyun Ah KIM
Author Information
1. Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea. kimha@hallym.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Chondrocytes;
Apoptosis;
Tumor Necrosis Factor;
Mitogen-Activated Protein Kinases
- MeSH:
Cell Death/*physiology;
Cells, Cultured;
Chondrocytes/cytology/*drug effects/metabolism;
Enzyme Activation;
Enzyme Inhibitors/metabolism;
Humans;
JNK Mitogen-Activated Protein Kinases/*metabolism;
NF-kappa B/metabolism;
Neoplasm Proteins/metabolism;
Proto-Oncogene Proteins c-bcl-2/metabolism;
Research Support, Non-U.S. Gov't;
Signal Transduction/physiology;
Tumor Necrosis Factor-alpha/*pharmacology
- From:Journal of Korean Medical Science
2004;19(4):567-573
- CountryRepublic of Korea
- Language:English
-
Abstract:
The aim of this study was to elucidate the role of JNK signaling pathway involved in tumor necrosis factor-alpha (TNF-alpha)-induced death of chondrocytes. Primary chondrocyte cultures were obtained from human knee osteoarthritis cartilages. First passage chondrocytes were treated with TNF-alpha and various potentiators, and cell death was measured with MTT assay. C-Jun N terminal kinase (JNK) activation was investigated with the solid phase kinase assay. Expression of apoptosis-related molecule was assayed with Western blot. Chondrocytes were resistant to TNF-alpha-induced cell death. In contrast, pretreatment with actinomycin D, the phosphatase inhibitor vanadate or MAP kinase phosphatase-1 (MKP-1) inhibitor Ro318220 invariably led to chondrocyte death. While TNF-alpha alone stimulated a single, brief JNK activity, a second JNK peak was observed when the cells were pretreated with actinomycin D. When the cells were pretreated with vanadate or Ro318220, TNF-alpha-induced JNK activation was greatly prolonged, which was associated with the induction of cell death. The expression of Bcl-2 and Mcl-1 decreased significantly in conditions of cell death. In conclusions, our data suggest that chondrocyte death induced by TNF-alpha is associated with sustained JNK activation. This effect may be due to downregulation of TNF-alpha induced phosphatase that inactivates JNK and of Bcl-2 family proteins.
