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
