Bile acid-mediated induction of cyclooxygenase-2 and Mcl-1 in hepatic stellate cells
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| Titel: | Bile acid-mediated induction of cyclooxygenase-2 and Mcl-1 in hepatic stellate cells |
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| Autoren: | Kim, Kang Mo, Yoon, Jung-Hwan, Gwak, Geum-Youn, Kim, Won, Lee, Sung Hee, Jang, Ja June, Lee, Hyo-Suk |
| Weitere Verfasser: | 김강모, 윤정환, 곽금윤, 김원, 이승희, 장자준, 이효석 |
| Verlagsinformationen: | Academic Press |
| Publikationsjahr: | 2006 |
| Bestand: | Seoul National University: S-Space |
| Schlagwörter: | 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 |
| Beschreibung: | 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. |
| Publikationsart: | article in journal/newspaper |
| Sprache: | English |
| Relation: | https://hdl.handle.net/10371/10034 |
| DOI: | 10.1016/j.bbrc.2006.02.072 |
| Verfügbarkeit: | https://hdl.handle.net/10371/10034 https://doi.org/10.1016/j.bbrc.2006.02.072 |
| Dokumentencode: | edsbas.C3E55F2A |
| Datenbank: | BASE |
Nájsť tento článok vo Web of Science | 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. |
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| DOI: | 10.1016/j.bbrc.2006.02.072 |