Hepatocyte-specific deficiency of SOD-2 causes liver failure and promotes tumorigenesis

In the mitochondrial matrix manganese superoxide dismutase (SOD-2) is the essential antioxidant enzyme that degrades reactive oxygen species. The liver has the highest specific MnSOD activity, which implies its important role for maintaining proper organ function and to prevent pathological situations such as cancer. In line with this, we generated hepatocyte-specific SOD-2 knockout mice and found that that ROS levels were enhanced in livers of SOD-2 lacking mice which were reduced in size and displayed signs of liver failure such as intracellular protein droplets, increased apoptotic bodies and Bax levels as well as multinuclear hepatocytes. Further, the zonation of glutamine synthetase, glucokinase and phosphoenolpyruvate carboxykinase was no longer preserved. Serum levels of enzymes indicating liver damage such as glutamate oxalacetate aminotransferase, glutamate pyruvate aminotransferase, cholinesterase, gamma glutamyltransferase, alkaline phosphatase were elevated compared to the control animals. In addition, bilirubin and albumin levels were also enhanced. Further, by using diethylnitrosamine as tumor-inducing agent we could show that tumor development was accelarated in mice with hepatocyte-specific lack of SOD-2.

hepatocyte - manganese superoxide dismutase - reactive oxygen species - tumor