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 (CCl4)-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 CCl4 injection to induce acute liver injury. Pin1 overexpression in the liver of the experimental mice attenuated acute liver injury induced by CCl4. 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 CCl4 by modulating apoptotic signals and by increasing NF-kB activity.