scholarly journals Up-regulation of Foxo4 mediated by hepatitis B virus X protein confers resistance to oxidative stress-induced cell death

2011 ◽  
Author(s):  
Young-Hwa Chung
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
X Protein ◽  
B Virus

scholarly journals Hepatitis B Virus X Protein Stimulates the Mitochondrial Translocation of Raf-1 via Oxidative Stress

2007 ◽  
Vol 81 (12) ◽  
pp. 6757-6760 ◽  
Author(s):  
Jun Chen ◽  
Aleem Siddiqui
Keyword(s):  
Oxidative Stress ◽  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Viral Genome ◽  
X Protein ◽  
Disease Pathogenesis ◽  
Mitochondrial Translocation ◽  
B Virus ◽  
Insight Into

ABSTRACT The human hepatitis B virus (HBV) X protein (HBx) plays a crucial role(s) in the viral life cycle and contributes to the onset of hepatocellular carcinoma (HCC). HBx caused the mitochondrial translocation of Raf-1 kinase either alone or in the context of whole-viral-genome transfections. Mitochondrial translocation of Raf-1 is mediated by HBx-induced oxidative stress and was dependent upon the phosphorylation of Raf-1 at the serine338/339 and Y340/341 residues by p21-activated protein kinase 1 and Src kinase, respectively. These studies provide an insight into the mechanisms by which HBV induces intracellular events relevant to liver disease pathogenesis, including HCC.

scholarly journals Mitochondrially Associated Hepatitis B Virus X Protein Constitutively Activates Transcription Factors STAT-3 and NF-κB via Oxidative Stress

2001 ◽  
Vol 21 (22) ◽  
pp. 7721-7730 ◽  
Author(s):  
Gulam Waris ◽  
Kyung-Won Huh ◽  
Aleem Siddiqui
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Pyrrolidine Dithiocarbamate ◽  
Voltage Dependent Anion Channel ◽  
X Protein ◽  
Mobility Shift ◽  
Mitochondrial Functions ◽  
B Virus

ABSTRACT The hepatitis B virus X protein (HBx) plays essential roles in viral replication and the generation of hepatocellular carcinoma. In spite of a large number of suggestive cellular targets and functions, a clear picture of its mechanism(s) of action has remained elusive. In this report, we continue to characterize its recently described mitochondrial association and further examine its impact on mitochondrial functions. HBx was previously shown to bind to a voltage-dependent anion channel (VDAC3) and alter the mitochondrial transmembrane potential (ΔΨm). Here we show that, as a consequence of association with mitochondria, HBx constitutively induces activation of transcription factors, which include STAT-3 and NF-κB. This induction of activation was sensitive to the antioxidantsN-acetyl l-cysteine and pyrrolidine dithiocarbamate, as well as to overexpression of Mn-superoxide dismutase. These results therefore implicate a potential role of reactive oxygen species (ROS) in a process that ultimately leads to the activation of STAT-3 and NF-κB. Evidence is also presented for the HBx-induced generation of ROS. The ability of HBx to induce the activation of STAT-3 and NF-κB was demonstrated by mobility shift and reporter gene expression assays with lysates from HBx-transfected HepG2 cells. A C-terminal HBx deletion mutant, HBxΔ99, failed to bind VDAC3 and activate STAT-3 and NF-κB. These studies shed new light on the physiological significance of HBx's mitochondrial association and its role in inducing oxidative stress which can contribute to the liver disease pathogenesis associated with the hepatitis B virus infection.

scholarly journals Hepatitis B virus X protein promotes liver cell pyroptosis under oxidative stress through NLRP3 inflammasome activation

2020 ◽  
Vol 69 (7) ◽  
pp. 683-696 ◽  
Author(s):  
Wen-hui Xie ◽  
Jian Ding ◽  
Xiao-xia Xie ◽  
Xiao-huang Yang ◽  
Xiao-Fan Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Liver Cell ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
X Protein ◽  
Nlrp3 Inflammasome Activation ◽  
B Virus

Blocking of G1/S transition and cell death in the regenerating liver of Hepatitis B virus X protein transgenic mice

2006 ◽  
Vol 340 (3) ◽  
pp. 916-928 ◽  
Author(s):  
Bo-Kuan Wu ◽  
Chao-Chin Li ◽  
Huei-Jane Chen ◽  
Junn-Liang Chang ◽  
King-Song Jeng ◽  
...  
Keyword(s):  
Cell Death ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Regenerating Liver ◽  
X Protein ◽  
B Virus

scholarly journals Hepatitis B Virus X Protein Increases 8-Oxo-7,8-Dihydro-2ʹ-Deoxyguanosine (8-Oxodg) Level via Repressing MTH1/ MTH2 Expression in Hepatocytes

2018 ◽  
Vol 51 (1) ◽  
pp. 80-96 ◽  
Author(s):  
Yan-Ting Lin ◽  
Wei Liu ◽  
Yun He ◽  
Yun-Li Wu ◽  
Wan-Nan Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Hbv Infection ◽  
Luciferase Reporter ◽  
Sequencing Analysis ◽  
X Protein ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Background/Aims: Chronic hepatitis B virus (HBV) infection markedly increases the risk of development of hepatocellular carcinoma (HCC). Among the seven viral proteins that HBV encodes, HBV X protein (HBx) appears to have the most oncogenic potential. The mitochondria-associated HBx can induce oxidative stress in hepatocytes, leading to the production of abundant reactive oxygen species (ROS). High levels of ROS usually induce oxidative DNA damage and 8-hydroxy-2-deoxyguanosine (8-OHdG), also known as 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG), which is one of the major products of DNA oxidation and an important biomarker for oxidative stress and carcinogenesis. Cells have evolved a mechanism to prevent oxidized nucleotides from their incorporation into DNA through nucleotide pool sanitization enzymes of MTH1 (NUDT1), MTH2 (NUDT15), MTH3 (NUDT18) and NUDT5. However, little is known as to whether HBx can regulate the expression of those enzymes and modulate the formation and accumulation of 8-oxodG in hepatocytes. Methods: The level of 8-oxodG was assessed by ELISA in stable HBV-producing hepatoma cell lines, an HBV infectious mouse model, HBV and HBx transgenic mice and HBV-infected patients versus their respective controls. Expression of MTH1, MTH2, MTH3 and NUDT5 was determined by a real-time quantitative PCR and western blot analysis. Transcriptional regulation of MTH1 and MTH2 expression by HBx and the effect of HBx on MTH1 and MTH2 promoter hypermethylation were examined using a luciferase reporter assay and bisulfite sequencing analysis. Results: In comparison with controls, significantly higher levels of 8-oxodG were detected in the genome and culture supernatant of stable HBV-producing HepG2.2.15 cells, in the sera and liver tissues of HBV infectious mice and HBV or HBx transgenic mice, and in the sera of HBV-infected patients. Expression of HBx in hepatocytes significantly increased 8-oxodG level and reduced the expression of MTH1 and MTH2 at both mRNA and protein levels. It was also demonstrated that HBx markedly attenuated the MTH1 or MTH2 promoter activities through hypermethylation. Furthermore, enhancement of 8-oxodG production by HBx was reversible by overexpression of MTH1 and MTH2. Conclusion: Our data show that HBx expression results in the accumulation of 8-oxodG in hepatocytes through inhibiting the expression of MTH1 and MTH2. This may implicate that HBx may act as a tumor promoter through facilitating the mutational potential of 8-oxodG thus connecting a possible link between HBV infection and liver carcinogenesis.

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