Overexpression of peptidyl-prolyl isomerase Pin1 attenuates hepatocytes apoptosis and secondary necrosis following carbon tetrachloride-induced acute liver injury in mice.

Pin1, a member of the parvulin family of PPIase enzymes, plays a crucial role in the post phosphorylation regulation that governs important roles in the cell signaling mechanism and regulates a variety of cellular events. In this study, we investigated the role of Pin1 in carbon tetrachloride (CCl(4))-induced apoptosis and necrosis of hepatocytes during acute liver injury of mice. An in vivo study was done with the overexpression of Pin1 in the mouse liver; using Pin1-adenoviruse (ad-Pin1) followed by CCl(4) injection to induce acute liver injury. Pin1 overexpression in the liver of the experimental mice attenuated acute liver injury induced by CCl(4) . Serum aminotransferases and the number of apoptotic cells were decreased compared to those of control virus injected mice. In addition, Pin1 overexpression increased NF-kB activity, as evidenced by increased DNA binding. In conclusion, Pin1 reduces acute liver injury of mice due to CCl(4) by modulating apoptotic signals and by increasing NF-kB activity.