Please use this identifier to cite or link to this item:
10.3390/v7062745
Title: | HCV core protein uses multiple mechanisms to induce oxidative stress in human hepatoma huh7 cells |
Authors: | Ivanov, Alexander V. Smirnova, Olga A. Petrushanko, Irina Y. Ivanova, Olga N. Karpenko, Inna L. Alekseeva, Ekaterina Sominskaya, Irina Makarov, Alexander A. Bartosch, Birke Kochetkov, Sergey N. Isaguliants, Maria G. Institute of Microbiology and Virology |
Keywords: | Cytochrome P450;ER oxidoreductin;Hepatitis C virus;NADPH oxidase;Oxidative stress;Reactive oxygen species;Transforming growth factor;3.1 Basic medicine;3.3 Health sciences;1.1. Scientific article indexed in Web of Science and/or Scopus database;Infectious Diseases;Virology;SDG 3 - Good Health and Well-being |
Issue Date: | 29-May-2015 |
Citation: | Ivanov , A V , Smirnova , O A , Petrushanko , I Y , Ivanova , O N , Karpenko , I L , Alekseeva , E , Sominskaya , I , Makarov , A A , Bartosch , B , Kochetkov , S N & Isaguliants , M G 2015 , ' HCV core protein uses multiple mechanisms to induce oxidative stress in human hepatoma huh7 cells ' , Viruses , vol. 7 , no. 6 , pp. 2745-2770 . https://doi.org/10.3390/v7062745 |
Abstract: | Hepatitis C virus (HCV) infection is accompanied by the induction of oxidative stress, mediated by several virus proteins, the most prominent being the nucleocapsid protein (HCV core). Here, using the truncated forms of HCV core, we have delineated several mechanisms by which it induces the oxidative stress. The N-terminal 36 amino acids of HCV core induced TGFβ1-dependent expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 1 and 4, both of which independently contributed to the production of reactive oxygen species (ROS). The same fragment also induced the expression of cyclo-oxygenase 2, which, however, made no input into ROS production. Amino acids 37–191 of HCV core up-regulated the transcription of a ROS generating enzyme cytochrome P450 2E1. Furthermore, the same fragment induced the expression of endoplasmic reticulum oxidoreductin 1α. The latter triggered efflux of Ca2+ from ER to mitochondria via mitochondrial Ca2+ uniporter, leading to generation of superoxide anions, and possibly also H2O2. Suppression of any of these pathways in cells expressing the full-length core protein led to a partial inhibition of ROS production. Thus, HCV core causes oxidative stress via several independent pathways, each mediated by a distinct region of the protein. |
Description: | Publisher Copyright: © 2015 by the authors; licensee MDPI, Basel, Switzerland. |
DOI: | 10.3390/v7062745 |
ISSN: | 1999-4915 |
Appears in Collections: | Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure |
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HCV_Core_Protein_Uses_Multiple_Mechanisms_to_Induce_Oxidative_Stress_in_Human_Hepatoma.pdf | 1.96 MB | Adobe PDF | View/Open |
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