Overexpression of Peptidyl-Prolyl Isomerase Pin1 Attenuates Hepatocytes Apoptosis and Secondary Necrosis Following Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Pathol Int. 2012 Jan;62(1):8-15. doi: 10.1111/j.1440-1827.2011.02744.x. Epub 2011 Nov 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / genetics
  • Carbon Tetrachloride
  • Cell Line
  • Chemical and Drug Induced Liver Injury / enzymology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology*
  • Hepatocytes / metabolism
  • Hepatocytes / pathology*
  • Male
  • Mice
  • Mice, Knockout
  • NF-kappa B / metabolism
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Necrosis
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism*
  • Transaminases / blood
  • Up-Regulation / genetics

Substances

  • NF-kappa B
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Carbon Tetrachloride
  • Transaminases
  • Peptidylprolyl Isomerase
  • Pin1 protein, mouse