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Open Access Green as soon as Postprint is submitted to ZB.
Tauro-β-muricholic acid restricts bile acid-induced hepatocellular apoptosis by preserving the mitochondrial membrane potential.
Biochem. Biophys. Res. Commun. 424, 758-764 (2012)
Purpose: beta-Muricholic acid (beta mcA) is a trihydroxylated bile acid that constitutes the major bile acid in rat and mouse. beta MCA is more hydrophilic than ursodeoxycholic acid and has been evaluated for dissolution of cholesterol gallstones. Since it is unknown if beta MCA has beneficial effects on hepatocyte cell death we determined the effect of tauro-beta MCA (T beta MCA) on apoptosis in vitro. Methods: Human Ntcp-transfected HepG2 cells and primary hepatocytes from rat and mouse were incubated with the proapoptotic glycochenodeoxycholic acid (GCDCA) as well as the free fatty acid palmitate in the absence and presence of T beta MCA. Apoptosis was quantified using caspase 3/7-assays and after Hoechst 33342 staining. The mitochondrial membrane potential (MMP) was measured fluorometrically using JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazol-carbocyaniniodide). Immunoblotting was performed against the proapoptotic Bcl-2-protein Bax. Results: In Ntcp-HepG2 cells, GCDCA markedly increased apoptosis after 4 h. Co-incubation with T beta MCA reduced apoptosis to 49% (p < 0.01 vs. GCDCA, each; n = 6). While GCDCA (100 mu mol/L) reduced the MMP to 34% after 6 h, combination treatment with T beta MCA restored the MMP to control levels at all time points (n = 4). T beta MCA also restored breakdown of the MMP induced by palmitate. GCDCA induced a translocation of Bax from the cytosol to mitochondria that was inhibited by simultaneous treatment with T beta MCA in eqimolar concentrations. Conclusions: T beta MCA restricts hepatocellular apoptosis induced by low micromolar concentrations of GCDCA or palmitate via inhibition of Bax translocation to mitochondria and preservation of the MMP. Thus, further studies are warranted to evaluate a potential use of T beta MCA in ameliorating liver injury in cholestasis.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Cholestasis ; Bile Acid ; Apoptosis ; Mitochondrial Membrane Potential; Primary Biliary-Cirrhosis; Primary Sclerosing Cholangitis; Human Hepatoma-Cells; Ursodeoxycholic Acid; Rat-Liver; Biochemical Response; Induced Cholestasis; Tauroursodeoxycholate; Cytoprotection; Hepatocytes
ISSN (print) / ISBN
0006-291X
e-ISSN
1090-2104
Quellenangaben
Volume: 424,
Issue: 4,
Pages: 758-764
Publisher
Elsevier
Non-patent literature
Publications
Reviewing status
Peer reviewed