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Bile acid-mediated induction of cyclooxygenase-2 and Mcl-1 in hepatic stellate cells
Cited 8 time in
Web of Science
Cited 10 time in Scopus
- Authors
- Issue Date
- 2006-02-21
- Publisher
- Academic Press
- Citation
- Biochem. Biophys. Res. Commun. 342 (2006) 1108-1113.
- Keywords
- Animals ; Apoptosis/drug effects/*physiology ; Cell Line ; Cell Survival/drug effects ; Chenodeoxycholic Acid/administration & dosage/*metabolism ; Cyclooxygenase 2/*metabolism ; Dose-Response Relationship, Drug ; Hepatocytes/drug effects/*metabolism ; Humans ; Neoplasm Proteins/*metabolism ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Rats ; Signal Transduction/drug effects/physiology
- Abstract
- In cholestatic liver diseases, bile acids induce hepatocyte apoptosis and thus cause liver injury, but hepatic stellate cells (HSCs) survive in the presence of bile acids. We attempted to analyze anti-apoptotic signaling pathways in HSCs against bile acid-induced apoptosis. In immortalized human HSCs and primarily cultured rat HSCs, bile acid treatment increased the expression levels of cyclooxygenase-2 (COX-2) and Mcl-1. COX-2 induction was found to be due to transcriptional enhancement dependent on p42/44, p38 MAPK, and JNK activation, whereas Mcl-1 induction resulted from bile acid-mediated protein stabilization in a Raf-1-dependent manner. Moreover, the inhibitions of either COX-2 activity by celecoxib or Mcl-1 induction by siRNA transfection rendered HSCs susceptible to bile acid-induced apoptosis. These results imply that the bile acid-mediated inductions of COX-2 and Mcl-1 may lead to HSC survival in cholestatic liver diseases.
- ISSN
- 0006-291X
- Language
- English
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