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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
Kim, Kang Mo; Yoon, Jung-Hwan; Gwak, Geum-Youn; Kim, Won; Lee, Sung Hee; Jang, Ja June; Lee, Hyo-Suk
Issue Date
2006-02-21
Publisher
Academic Press
Citation
Biochem. Biophys. Res. Commun. 342 (2006) 1108-1113.
Keywords
AnimalsApoptosis/drug effects/*physiologyCell LineCell Survival/drug effectsChenodeoxycholic Acid/administration & dosage/*metabolismCyclooxygenase 2/*metabolismDose-Response Relationship, DrugHepatocytes/drug effects/*metabolismHumansNeoplasm Proteins/*metabolismProto-Oncogene Proteins c-bcl-2/*metabolismRatsSignal 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
URI
http://hdl.handle.net/10371/10034
DOI
https://doi.org/10.1016/j.bbrc.2006.02.072
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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