Please use this identifier to cite or link to this item: 10.1371/journal.pone.0024957
Title: Hepatitis C virus proteins activate NRF2/ARE pathway by distinct ROS-dependent and independent mechanisms in HUH7 cells
Authors: Ivanov, Alexander V.
Smirnova, Olga A.
Ivanova, Olga N.
Masalova, Olga V.
Kochetkov, Sergey N.
Isaguliants, Maria G.
Keywords: 1.6 Biological sciences;3.4 Medical biotechnology;1.1. Scientific article indexed in Web of Science and/or Scopus database;General Biochemistry,Genetics and Molecular Biology;General Agricultural and Biological Sciences;General;SDG 3 - Good Health and Well-being
Issue Date: 13-Sep-2011
Citation: Ivanov , A V , Smirnova , O A , Ivanova , O N , Masalova , O V , Kochetkov , S N & Isaguliants , M G 2011 , ' Hepatitis C virus proteins activate NRF2/ARE pathway by distinct ROS-dependent and independent mechanisms in HUH7 cells ' , PloS one , vol. 6 , no. 9 , e24957 . https://doi.org/10.1371/journal.pone.0024957
Abstract: Hepatitis C virus (HCV) is a highly pathogenic human virus associated with liver fibrosis, steatosis, and cancer. In infected cells HCV induces oxidative stress. Here, we show that HCV proteins core, E1, E2, NS4B, and NS5A activate antioxidant defense Nrf2/ARE pathway via several independent mechanisms. This was demonstrated by the analysis of transient co-expression in Huh7 cells of HCV proteins and luciferase reporters. Expression, controlled by the promoters of stress-response genes or their minimal Nrf2-responsive elements, was studied using luminescence assay, RT-qPCR and/or Western-blot analysis. All five proteins induced Nrf2 activation by protein kinase C in response to accumulation of reactive oxygen species (ROS). In addition, expression of core, E1, E2, NS4B, and NS5A proteins resulted in the activation of Nrf2 in a ROS-independent manner. The effect of core and NS5A was mediated through casein kinase 2 and phosphoinositide-3 kinase, whereas those of NS4B, E1, and E2, were not mediated by either PKC, CK2, PI3K, p38, or ERK. Altogether, on the earliest stage of expression HCV proteins induced a strong up-regulation of the antioxidant defense system. These events may underlie the harmful effects of HCV-induced oxidative stress during acute stage of hepatitis C.
DOI: 10.1371/journal.pone.0024957
ISSN: 1932-6203
Appears in Collections:Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.