Ibrahim, Sara and Dayoub, Rania and Krautbauer, Sabrina and Liebisch, Gerhard and Wege, Anja Kathrin and Melter, Michael and Weiss, Thomas S. (2019) Bile acid-induced apoptosis and bile acid synthesis are reduced by over-expression of Augmenter of Liver Regeneration (ALR) in a STAT3-dependent mechanism. EXPERIMENTAL CELL RESEARCH, 374 (1). pp. 189-197. ISSN 0014-4827, 1090-2422
Full text not available from this repository. (Request a copy)Abstract
Cholestasis represents pathophysiologic syndromes defined as an impaired bile flow from the liver. As an outcome, bile acids accumulate and promote hepatocytes injury followed by liver cirrhosis and liver failure. Bile acids induce apoptosis, ER stress and mitochondrial membrane instability. In this study we aimed to investigate the role of cytosolic short form of ALR (Augmenter of Liver Regeneration) in the synthesis of bile acids and bile acid-induced apoptosis. Human hepatoma cells over-expressing the short form of ALR (sfALR, 15 kDa) were incubated with glycochenodeoxycholic acid (GCDCA), and then primary bile acids' production and apoptosis were analyzed. High levels of cytosolic sfALR reduced CYP7A1 mRNA expression and bile acids levels, the ratelimiting enzyme in the classic pathway of bile acid synthesis. This reduction was attributed to STAT3 (signal transducer and activator of transcription 3) activation and reduction of HNF4 alpha (Hepatocyte nuclear factor 4 alpha). Furthermore, apoptosis induction by GCDCA and TRAIL was reduced in cells over-expressing sfALR which was attributed to reduced expression of death receptor 5 (DR5). We found decreased hepatic mRNA levels of ALR and FOXA2 (Forkhead Box A2), an inducer of ALR expression, in human cholestatic liver samples which might explain the increased accumulation of bile acids and bile acid-induced apoptosis in cholestasis patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATOCYTE APOPTOSIS; GROWTH-FACTOR; NUCLEAR RECEPTORS; GENE; CHOLESTEROL; CHOLESTASIS; ACTIVATION; MOUSE; REPRESSION; INHIBITION; Augmenter of liver regeneration; Cholestasis; Apoptosis; STAT3; FOXA2 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Lehrstuhl für Kinder- und Jugendmedizin Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Apr 2020 06:52 |
| Last Modified: | 22 Apr 2020 06:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27887 |
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