Carvajal-Yepes, Monica and Himmelsbach, Kiyoshi and Schaedler, Stephanie and Ploen, Daniela and Krause, Janis and Ludwig, Leopold and Weiss, Thomas and Klingel, Karin and Hildt, Eberhard (2011) Hepatitis C Virus Impairs the Induction of Cytoprotective Nrf2 Target Genes by Delocalization of Small Maf Proteins. JOURNAL OF BIOLOGICAL CHEMISTRY, 286 (11). pp. 8941-8951. ISSN 0021-9258, 1083-351X
Full text not available from this repository. (Request a copy)Abstract
The expression of a variety of cytoprotective genes is regulated by short cis-acting elements in their promoters, called antioxidant response elements (AREs). A central regulator of ARE-mediated gene expression is the NF-E2-related factor 2 (Nrf2). Nrf2/ARE-regulated genes are crucial for the maintenance of cellular integrity. Hepatitis C virus inhibits the induction of ARE-regulated genes, but neither induction nor inhibition of ARE-regulated gene expression affects HCV replication directly. In HCV-replicating cells the core protein triggers the delocalization of sMaf proteins from the nucleus to the replicon complex. Here sMafs bind to NS3. The extranuclear sMaf proteins prevent Nrf2 from entry in the nucleus and thereby inhibit the induction of Nrf2/ARE-regulated genes. This results in the decreased expression of cytoprotective genes. Consistent with this finding, the elimination of ROI is impaired in HCV-replicating cells as demonstrated by elevated protein oxidation or 8-OH-dG formation, reflecting DNA damage. In conclusion, these data identified a novel mechanism of Nrf2 regulation and suggest that the HCV-dependent inhibition of Nrf2/ARE-regulated genes confers to the HCV-associated pathogenesis by elevation of intracellular ROI that affect integrity of the host genome and regenerative processes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANTIOXIDANT RESPONSE; B-VIRUS; HUMAN HEPATOCYTES; OXIDATIVE STRESS; VIRAL-HEPATITIS; RNA REPLICATION; NS5A; ACTIVATION; PROTEASOME; EXPRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Jun 2020 05:14 |
| Last Modified: | 24 Jun 2020 05:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21108 |
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