Hepatitis C Virus NS5A Protein Triggers Oxidative Stress by Inducing NADPH Oxidases 1 and 4 and Cytochrome P450 2E1
Joint Authors
Bartosch, Birke
Smirnova, Olga A.
Ivanova, Olga N.
Valuev-Elliston, Vladimir T.
Mukhtarov, Furkat
Kochetkov, Sergey N.
Ivanov, Alexander V.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-04-20
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Replication of hepatitis C virus (HCV) is associated with the induction of oxidative stress, which is thought to play a major role in various liver pathologies associated with chronic hepatitis C.
NS5A protein of the virus is one of the two key viral proteins that are known to trigger production of reactive oxygen species (ROS).
To date it has been considered that NS5A induces oxidative stress by altering calcium homeostasis.
Herein we show that NS5A-induced oxidative stress was only moderately inhibited by the intracellular calcium chelator BAPTA-AM and not at all inhibited by the drug that blocks the Ca2+ flux from ER to mitochondria.
Furthermore, ROS production was not accompanied by induction of ER oxidoreductins (Ero1), H2O2-producing enzymes that are implicated in the regulation of calcium fluxes.
Instead, we found that NS5A contributes to ROS production by activating expression of NADPH oxidases 1 and 4 as well as cytochrome P450 2E1.
These effects were mediated by domain I of NS5A protein.
NOX1 and NOX4 induction was mediated by enhanced production of transforming growth factor β1 (TGFβ1).
Thus, our data show that NS5A protein induces oxidative stress by several multistep mechanisms.
American Psychological Association (APA)
Smirnova, Olga A.& Ivanova, Olga N.& Bartosch, Birke& Valuev-Elliston, Vladimir T.& Mukhtarov, Furkat& Kochetkov, Sergey N.…[et al.]. 2016. Hepatitis C Virus NS5A Protein Triggers Oxidative Stress by Inducing NADPH Oxidases 1 and 4 and Cytochrome P450 2E1. Oxidative Medicine and Cellular Longevity،Vol. 2016, no. 2016, pp.1-10.
https://search.emarefa.net/detail/BIM-1114333
Modern Language Association (MLA)
Smirnova, Olga A.…[et al.]. Hepatitis C Virus NS5A Protein Triggers Oxidative Stress by Inducing NADPH Oxidases 1 and 4 and Cytochrome P450 2E1. Oxidative Medicine and Cellular Longevity No. 2016 (2016), pp.1-10.
https://search.emarefa.net/detail/BIM-1114333
American Medical Association (AMA)
Smirnova, Olga A.& Ivanova, Olga N.& Bartosch, Birke& Valuev-Elliston, Vladimir T.& Mukhtarov, Furkat& Kochetkov, Sergey N.…[et al.]. Hepatitis C Virus NS5A Protein Triggers Oxidative Stress by Inducing NADPH Oxidases 1 and 4 and Cytochrome P450 2E1. Oxidative Medicine and Cellular Longevity. 2016. Vol. 2016, no. 2016, pp.1-10.
https://search.emarefa.net/detail/BIM-1114333
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1114333