Prologation of c-Jun N-Terminal Kinase is Associated with Cell Death Induced by Tumor Necrosis Factor Alpha in Human Chondrocytes
Journal of Korean Medical Science
;
: 567-573, 2004.
Article
in English
| WPRIM
| ID: wpr-109225
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Signal Transduction
/
Cells, Cultured
/
NF-kappa B
/
Tumor Necrosis Factor-alpha
/
Cell Death
/
Proto-Oncogene Proteins c-bcl-2
/
Chondrocytes
/
JNK Mitogen-Activated Protein Kinases
/
Enzyme Activation
/
Enzyme Inhibitors
Limits:
Humans
Language:
English
Journal:
Journal of Korean Medical Science
Year:
2004
Type:
Article
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