Role of hepatocyte NADPH Oxidase 4 in oxidative stress and DNA damage by genotype 1a hepatitis C virus

摘要: Hepatitis C virus (HCV) infection can lead to chronic resulting in severe liver diseases, including cirrhosis and hepatocellular carcinoma (HCC). Chronic hepatitis (CHC) is characterized by ongoing inflammation generation of reactive oxygen species (ROS) such as superoxide (O2.-) hydrogen peroxide (H2O2). NADPH oxidase (Nox) enzymes produce ROS their primary function have been associated with oxidative stress CHC. However, the precise role that Nox play pathogenesis HCC still unclear. We show structural core protein genotype 1a HCV sufficient elevate Nox1 4 mRNA, expression, enzyme activity H2O2 levels vitro. Human hepatocytes constitutively expressing exhibited elevated Nox4 nucleus increased DNA damage markers. Furthermore, novel Nox-specific inhibitor VAS-2870 was capable decreasing core-associated increase activity. Altogether, these results highlight importance developing therapeutic agents targeting for use adjunct treatment CHC prevent carcinogenesis.