Augmenter of Liver Regeneration (ALR) regulates bile acid synthesis and attenuates bile acid-induced apoptosis via glycogen synthase kinase-3 β (GSK-3β) inhibition.

Augmenter of Liver Regeneration (ALR) regulates bile acid synthesis and attenuates bile acid-induced apoptosis via glycogen synthase kinase-3β (GSK-3β) inhibition. Exp Cell Res. 2020 Oct 24;397(1):112343 Authors: Ibrahim S, Dayoub R, Saberi V, Buchner M, Melter M, Weiss TS Abstract Bile acid synthesis is restricted to hepatocytes and is rate-limited by CYP7A1 (cholesterol 7α hydroxylase). CYP7A1 expression undergoes tight regulation and is repressed after partial hepatectomy to prevent the accumulation of toxic bile acids. Augmenter of Liver Regeneration (ALR) is a hepatotrophic factor shown to support liver regeneration by augmenting cell proliferation and reducing apoptosis. Nevertheless, less is known about ALR's role in protecting hepatocytes from bile acid accumulation and bile acid-induced apoptosis. Therefore, HepG2 and Huh-7 cells were incubated with recombinant human ALR (rALR) and the expression of CYP7A1, bile acid-induced apoptosis as well as potential molecular mechanisms were analyzed. We found that rALR reduces CYP7A1 expression by increasing nuclear NFκB levels. Moreover, rALR reduced glycochenodeoxycholate (GCDC)-induced-apoptosis by decreased expression of pro-apoptotic Bax and enhanced expression of anti-apoptotic Mcl-1, which is regulated by phosphatidylinositol-3-kinase (PI3K)/Akt activation and glycogen synthase kinase-3β (GSK3β) phosphorylation. Inhibitors for PI3K/Akt (GSK690693) and GSK3β (SB415286) c...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research