FIGURE 4.
Yap1 loss in hepatocytes is associated with enhanced hepatotoxicity and downregulation of detoxification enzymes including Aldh1a1 after ethanol/CCl4 treatment. (A) The ethanol‐fed Yap1 null livers lost both pericentral and periportal induction of Yap protein post CCl4 intoxication, and exhibited elevated levels of lipid peroxidation as indicated by stronger staining of HNE‐adducts than controls. Scale bar: 100 μm. Areas immunoreactive to antibodies for Yap or HNE were quantified, and the percentages of positive areas were calculated as means ± SEM based on quantification of images from more than 10 fields (100× magnification) from 5 mice per group. *p < .05; **p < .01; ***p < .001. (B–E) Enhanced production of hepatic MDA (B), ROS (C), and acetaldehyde (D) were associated with decreased cytosolic Aldh activity (E) in the damaged Yap1 KO livers. (F and G) Downregulation of Adh1, Aldh1a1, and Drs3 were found at mRNA in Q‐RT‐PCR analysis (F) and protein levels in immunoblotting (G). Values in (B–F) represent means ± SD (n = 5 mice per group). *p < .05