Journal of Hepatology

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Differential contribution of hepatitis C virus NS5A and core proteins to the induction of oxidative and nitrosative stress in human hepatocyte-derived cells, 27 June 2005
García-Mediavilla MV, Sánchez-Campos S, González-Pérez P, Gómez-Gonzalo M, Majano PL, López-Cabrera M, Clemente G, García-Monzón C, González-Gallego J
pages 606-613
Background/Aims
We aimed to explore the effects of hepatitis C virus (HCV) core and NS5A proteins on reactive oxygen (ROS) and nitrogen species (RNS) formation and on gene expression profile of iNOS in human hepatocyte-derived cells.
Methods
Production of ROS and RNS and nitrotyrosine residues accumulation were determined by flow cytometry and fluorescent microscopy as well as by Western blot, respectively, in NS5A- and core-transfected cells. Northern blot, Western blot, real-time PCR, and luciferase assays were used to assess iNOS gene expression in both transfectants.
Results
Cytokine-activated NS5A- and core-transfected cells induced ROS and RNS production but an earlier and more marked increase was observed in NS5A-expressing cells. Superoxide production was also augmented, showing a similar temporal pattern of appearance in both NS5A- and core-transfected cells. Although both NS5A and core HCV proteins were able to up-regulate iNOS gene expression, accompanied by a nitrotyrosine-containing proteins accumulation, an earlier iNOS overexpression was observed in NS5A-expressing cells, suggesting a different time course of iNOS activation pattern for core and NS5A HCV proteins.
Conclusions
Our results indicate a differential contribution of both HCV proteins to oxidative and nitrosative stress generation.