Abstract | BACKGROUND: Apoptotic cell death and c-Jun N-terminal kinase (JNK) activation occur after hepatic ischemia/reperfusion injury. In other cell types, JNK activation was shown to be required for apoptosis. This study tested the hypotheses that JNK contributes to hepatocellular apoptosis, and that inhibition of JNK activity improves cell viability. METHODS: RESULTS: CONCLUSIONS: These data show that pharmacologic inhibition of JNK activity reduces bile salt or TNF-alpha-induced apoptosis by maintaining expression of anti-apoptotic proteins. The results indicate that JNK is an important component of the apoptosis signaling cascade and suggest a possible therapeutic strategy in certain liver disorders.
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Authors | Eric L Marderstein, Brian Bucher, Zhong Guo, Xuesheng Feng, Kaye Reid, David A Geller |
Journal | Surgery
(Surgery)
Vol. 134
Issue 2
Pg. 280-4
(Aug 2003)
ISSN: 0039-6060 [Print] United States |
PMID | 12947330
(Publication Type: Journal Article)
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Chemical References |
- Anthracenes
- Enzyme Inhibitors
- Proteins
- Proto-Oncogene Proteins c-bcl-2
- Tumor Necrosis Factor-alpha
- Tumor Suppressor Protein p53
- X-Linked Inhibitor of Apoptosis Protein
- Dactinomycin
- pyrazolanthrone
- JNK Mitogen-Activated Protein Kinases
- Mitogen-Activated Protein Kinases
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Topics |
- Animals
- Anthracenes
(pharmacology)
- Apoptosis
(drug effects)
- Cell Survival
(drug effects)
- Cells, Cultured
- Dactinomycin
(pharmacology)
- Enzyme Inhibitors
(pharmacology)
- Hepatocytes
(drug effects, enzymology, metabolism, physiology)
- JNK Mitogen-Activated Protein Kinases
- Male
- Mitogen-Activated Protein Kinases
(antagonists & inhibitors)
- Proteins
(metabolism)
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Tumor Necrosis Factor-alpha
(pharmacology)
- Tumor Suppressor Protein p53
(metabolism)
- X-Linked Inhibitor of Apoptosis Protein
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