| Literature DB >> 19051025 |
Alisan Kahraman1, Justin L Mott, Steven F Bronk, Nathan W Werneburg, Fernando J Barreyro, Maria E Guicciardi, Yuko Akazawa, Karen Braley, Ruth W Craig, Gregory J Gores.
Abstract
Hepatocyte apoptosis contributes to liver injury and fibrosis after cholestatic injury. Our aim was to ascertain if the anti-apoptotic protein Mcl-1 alters liver injury or fibrosis in the bile duct-ligated mouse. Markers of apoptosis and fibrosis were compared in wild-type and transgenic mice expressing human Mcl-1 after bile duct ligation. Compared to hMcl-1 transgenic animals, ligated wild-type mice displayed a significant increase in TUNEL-positive cells and in caspase 3/7-positive hepatocytes. Consistent with apoptotic injury, the pro-apoptotic protein Bak underwent a conformational change to an activated form upon cholestatic injury, a change mitigated by hMcl-1 overexpression. Likewise, liver histology, number of bile infarcts, serum ALT values, markers of hepatic fibrosis, and animal survival were improved in bile duct-ligated mice transgenic for hMcl-1 as compared to wild-type mice. In conclusion, increased Mcl-1 expression plays a role in hepatoprotection upon cholestatic liver injury.Entities:
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Year: 2008 PMID： 19051025 PMCID： PMC2879585 DOI： 10.1007/s10620-008-0583-5
Source DB: PubMed Journal: Dig Dis Sci ISSN： 0163-2116 Impact factor: 3.199