Hepatitis C virus E2 protein induce reactive oxygen species (ROS)-related fibrogenesis in the HSC-T6 hepatic stellate cell line

2011 ◽  
Vol 112 (1) ◽  
pp. 233-243 ◽  
Author(s):  
Hsieh Ming-Ju ◽  
Hsieh Yih-Shou ◽  
Chen Tzy-Yen ◽  
Chiou Hui-Ling
Keyword(s):  
Reactive Oxygen Species ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cell Line ◽  
Hepatic Stellate Cell ◽  
Stellate Cell ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
E2 Protein

scholarly journals Oxidative Stress Attenuates Lipid Synthesis and Increases Mitochondrial Fatty Acid Oxidation in Hepatoma Cells Infected with Hepatitis C Virus

2015 ◽  
Vol 291 (4) ◽  
pp. 1974-1990 ◽  
Author(s):  
Donna N. Douglas ◽  
Christopher Hao Pu ◽  
Jamie T. Lewis ◽  
Rakesh Bhat ◽  
Anwar Anwar-Mohamed ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Growth Arrest ◽  
Lipid Synthesis ◽  
Reactive Oxygen ◽  
Hcv Infection ◽  
Peroxisome Proliferator ◽  
Oxygen Species ◽  
Peroxisome Proliferator Activated Receptor

Cytopathic effects are currently believed to contribute to hepatitis C virus (HCV)-induced liver injury and are readily observed in Huh7.5 cells infected with the JFH-1 HCV strain, manifesting as apoptosis highly correlated with growth arrest. Reactive oxygen species, which are induced by HCV infection, have recently emerged as activators of AMP-activated protein kinase. The net effect is ATP conservation via on/off switching of metabolic pathways that produce/consume ATP. Depending on the scenario, this can have either pro-survival or pro-apoptotic effects. We demonstrate reactive oxygen species-mediated activation of AMP-activated kinase in Huh7.5 cells during HCV (JFH-1)-induced growth arrest. Metabolic labeling experiments provided direct evidence that lipid synthesis is attenuated, and β-oxidation is enhanced in these cells. A striking increase in nuclear peroxisome proliferator-activated receptor α, which plays a dominant role in the expression of β-oxidation genes after ligand-induced activation, was also observed, and we provide evidence that peroxisome proliferator-activated receptor α is constitutively activated in these cells. The combination of attenuated lipid synthesis and enhanced β-oxidation is not conducive to lipid accumulation, yet cellular lipids still accumulated during this stage of infection. Notably, the serum in the culture media was the only available source for polyunsaturated fatty acids, which were elevated (2-fold) in the infected cells, implicating altered lipid import/export pathways in these cells. This study also provided the first in vivo evidence for enhanced β-oxidation during HCV infection because HCV-infected SCID/Alb-uPA mice accumulated higher plasma ketones while fasting than did control mice. Overall, this study highlights the reprogramming of hepatocellular lipid metabolism and bioenergetics during HCV infection, which are predicted to impact both the HCV life cycle and pathogenesis.

scholarly journals Reactive oxygen species suppress hepatitis C virus RNA replication in human hepatoma cells

Hepatology ◽  
2004 ◽  
Vol 39 (1) ◽  
pp. 81-89 ◽  
Author(s):  
Jinah Choi ◽  
Ki Jeong Lee ◽  
Yanyan Zheng ◽  
Ardath K. Yamaga ◽  
Michael M.C. Lai ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Reactive Oxygen ◽  
Rna Replication ◽  
Oxygen Species ◽  
Human Hepatoma ◽  
Hepatitis C Virus Rna ◽  
Human Hepatoma Cells ◽  
Virus Rna

scholarly journals Hepatitis C Virus Core Protein Inhibits Mitochondrial Electron Transport and Increases Reactive Oxygen Species (ROS) Production

2005 ◽  
Vol 280 (45) ◽  
pp. 37481-37488 ◽  
Author(s):  
Masaaki Korenaga ◽  
Ting Wang ◽  
Yanchun Li ◽  
Lori A. Showalter ◽  
Tehsheng Chan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Electron Transport ◽  
Core Protein ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Virus Core

Role of reactive oxygen species in zinc deficiency-induced hepatic stellate cell activation

2005 ◽  
Vol 39 (5) ◽  
pp. 631-640 ◽  
Author(s):  
Akiko Kojima-Yuasa ◽  
Kanako Umeda ◽  
Tomoko Ohkita ◽  
David Opare Kennedy ◽  
Shuhei Nishiguchi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Zinc Deficiency ◽  
Hepatic Stellate Cell ◽  
Cell Activation ◽  
Stellate Cell ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Hepatic Stellate Cell Activation

scholarly journals Nitric oxide promotes caspase-independent hepatic stellate cell apoptosis through the generation of reactive oxygen species

Hepatology ◽  
2008 ◽  
Vol 47 (6) ◽  
pp. 1983-1993 ◽  
Author(s):  
Daniel A. Langer ◽  
Amitava Das ◽  
David Semela ◽  
Ningling Kang-Decker ◽  
Helen Hendrickson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Hepatic Stellate Cell ◽  
Cell Apoptosis ◽  
Stellate Cell ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Hepatocyte NAD(P)H oxidases as an endogenous source of reactive oxygen species during hepatitis C virus infection

Hepatology ◽  
2010 ◽  
Vol 52 (1) ◽  
pp. 47-59 ◽  
Author(s):  
Nabora Soledad Reyes de Mochel ◽  
Scott Seronello ◽  
Shelley Hsiuying Wang ◽  
Chieri Ito ◽  
Jasper Xi Zheng ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Hepatitis C Virus Infection

scholarly journals Hepatitis C Virus Triggers Mitochondrial Permeability Transition with Production of Reactive Oxygen Species, Leading to DNA Damage and STAT3 Activation

2006 ◽  
Vol 80 (14) ◽  
pp. 7199-7207 ◽  
Author(s):  
Keigo Machida ◽  
Kevin T.-H. Cheng ◽  
Chao-Kuen Lai ◽  
King-Song Jeng ◽  
Vicky M.-H. Sung ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Reactive Oxygen ◽  
Mitochondrial Damage ◽  
Hcv Infection ◽  
Oxygen Species ◽  
Dna Breaks ◽  
Infected Cells

ABSTRACT Hepatitis C virus (HCV) infection is frequently associated with the development of hepatocellular carcinomas and non-Hodgkin's B-cell lymphomas. Previously, we reported that HCV infection causes cellular DNA damage and mutations, which are mediated by nitric oxide (NO). NO often damages mitochondria, leading to induction of double-stranded DNA breaks (DSBs) and accumulation of oxidative DNA damage. Here we report that HCV infection causes production of reactive oxygen species (ROS) and lowering of mitochondrial transmembrane potential (ΔΨm) in in vitro HCV-infected cell cultures. The changes in membrane potential could be inhibited by BCL-2. Furthermore, an inhibitor of ROS production, antioxidant N-acetyl-l-cysteine (NAC), or an inhibitor of NO, 1400W, prevented the alterations of ΔΨm. The HCV-induced DSB was also abolished by a combination of NO and ROS inhibitors. These results indicated that the mitochondrial damage and DSBs in HCV-infected cells were mediated by both NO and ROS. Among the HCV proteins, core, E1, and NS3 are potent ROS inducers: their expression led to DNA damage and activation of STAT3. Correspondingly, core-protein-transgenic mice showed elevated levels of lipid peroxidation and oxidatively damaged DNA. These HCV studies thus identified ROS, along with the previously identified NO, as the primary inducers of DSBs and mitochondrial damage in HCV-infected cells.

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