scholarly journals HBV Upregulates CtBP2 Expression via the X Gene

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Xinghui Liu ◽  
Chengliang Zhu ◽  
Jie Li ◽  
Fengxia Xu ◽  
Gang Huang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Hepatoma Cell ◽  
Infectious Clone ◽  
Single Gene ◽  
Gene Promoter ◽  
Hepatoma Cell Line ◽  
Human Hepatoma Cell ◽  
Activation Effect ◽  
Mrna And Protein Expression ◽  
X Gene

Background. Hepatitis B virus (HBV) infection causes acute and chronic liver diseases that can eventually develop into cirrhosis and hepatocellular carcinoma (HCC), but the carcinogenesis of HBV is not fully understood. Carboxyl-terminal-binding protein 2 (CtBP2) plays an important role in tumorigenesis and progression. The aim of this study was to investigate the effect of HBV on CtBP2 expression and to explore its mechanism.Methods. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting were used to evaluate the CtBP2 mRNA and protein expression levels in tissues and cells. The HBV infectious clone pHBV1.3 and plasmids expressing a single gene of the HBV genome were cotransfected with the CtBP2 gene promoter pGL3-CtBP2 into the human hepatoma cell line HepG2, and luciferase activity was determined using a luminometer.Results. CtBP2 expression was higher in HBV-related HCC tissues than in paracancerous tissues. CtBP2 expression was higher in HepG2.2.15 cells integrated with the HBV genome than in HepG2 cells. pHBV1.3 upregulated CtBP2 mRNA and protein expression. The HBV X gene significantly activated CtBP2 gene promoter activity, and CtBP2 mRNA and protein expression were upregulated by the HBV X gene. This activation effect was enhanced by the increase in the dose of the X gene, showing metrological dependence.Conclusion. HBV may be involved in the occurrence and development of HCC by upregulating CtBP2 expression.

Inhibition of interferon-α-induced signaling by hyperosmolarity and hydrophobic bile acids

2010 ◽  
Vol 391 (10) ◽  
Author(s):  
Dirk Graf ◽  
Katrin Haselow ◽  
Ivo Münks ◽  
Johannes G. Bode ◽  
Dieter Häussinger
Keyword(s):  
Protein Expression ◽  
Bile Acids ◽  
Hepatoma Cell ◽  
Protein A ◽  
Sodium Taurocholate ◽  
Inhibitory Effect ◽  
Interferon Α ◽  
Hepatoma Cell Line ◽  
Human Hepatoma Cell ◽  
Mrna And Protein Expression

Abstract Apart from viral conditions, host factors such as elevated bile acid concentrations are determinants of successful interferon-α (IFN-α) treatment in patients with chronic hepatitis C or B. The present study demonstrates that hydrophobic bile acids inhibit Jak1- and Tyk2-phosphorylation, which lead to blockade of STAT1-mediated IFN-α-signaling in the sodium-taurocholate cotransporting peptide (NTCP)-transfected human hepatoma cell line HepG2, resulting in a decreased mRNA and protein expression of IFN-stimulated genes such as myxovirus resistance protein A (MxA) or dsRNA-activated protein kinase (PKR). In addition, hyperosmotic stress leads to an inhibition of IFN-α-induced Jak1- and Tyk2-phosphorylation, and STAT1/STAT2-phosphorylation and gene expression. This inhibitory effect of hydrophobic bile acids or hyperosmolarity is not due to caspase-mediated cleavage or lysosomal degradation of the cognate receptors or to the generation of oxidative stress, activation of p38- or Erk-mediated MAPK pathways or phosphatase activity. Preincubation with the organic osmolyte betaine blocked the inhibitory effect of bile acids or hyperosmolarity on MxA protein expression, but had no effect on transcript levels or activation of STAT1, suggesting that betaine mediates its effects on MxA expression at a translational or post-translational level. Our findings could provide a rationale for betaine use in cholestatic HBV/HCV patients undergoing interferon therapy.

scholarly journals Stimulation of de novo glutathione synthesis by nitrofurantoin for enhanced resilience of hepatocytes

2021 ◽  
Author(s):  
Lukas S. Wijaya ◽  
Carina Rau ◽  
Theresa S. Braun ◽  
Serif Marangoz ◽  
Vincent Spegg ◽  
...  
Keyword(s):  
De Novo ◽  
Hepatoma Cell ◽  
Proteasome Inhibitors ◽  
Essential Element ◽  
Hepatoma Cell Line ◽  
Related Factor ◽  
Human Hepatoma Cell ◽  
Intact Cells ◽  
Intracellular Glutathione ◽  
Endogenous Antioxidant

AbstractToxicity is not only a function of damage mechanisms, but is also determined by cellular resilience factors. Glutathione has been reported as essential element to counteract negative influences. The present work hence pursued the question how intracellular glutathione can be elevated transiently to render cells more resistant toward harmful conditions. The antibiotic nitrofurantoin (NFT) was identified to stimulate de novo synthesis of glutathione in the human hepatoma cell line, HepG2, and in primary human hepatocytes. In intact cells, activation of NFT yielded a radical anion, which subsequently initiated nuclear-factor-erythroid 2-related-factor-2 (Nrf2)-dependent induction of glutamate cysteine ligase (GCL). Application of siRNA-based intervention approaches confirmed the involvement of the Nrf2-GCL axis in the observed elevation of intracellular glutathione levels. Quantitative activation of Nrf2 by NFT, and the subsequent rise in glutathione, were similar as observed with the potent experimental Nrf2 activator diethyl maleate. The elevation of glutathione levels, observed even 48 h after withdrawal of NFT, rendered cells resistant to different stressors such as the mitochondrial inhibitor rotenone, the redox cycler paraquat, the proteasome inhibitors MG-132 or bortezomib, or high concentrations of NFT. Repurpose of the antibiotic NFT as activator of Nrf2 could thus be a promising strategy for a transient and targeted activation of the endogenous antioxidant machinery.

scholarly journals Pyrrolizidine Alkaloids Induce Cell Death in Human HepaRG Cells in a Structure-Dependent Manner

2020 ◽  
Vol 22 (1) ◽  
pp. 202
Author(s):  
Josephin Glück ◽  
Julia Waizenegger ◽  
Albert Braeuning ◽  
Stefanie Hessel-Pras
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Pyrrolizidine Alkaloids ◽  
Defense Mechanism ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Human Hepatoma Cell

Pyrrolizidine alkaloids (PAs) are a group of secondary metabolites produced in various plant species as a defense mechanism against herbivores. PAs consist of a necine base, which is esterified with one or two necine acids. Humans are exposed to PAs by consumption of contaminated food. PA intoxication in humans causes acute and chronic hepatotoxicity. It is considered that enzymatic PA toxification in hepatocytes is structure-dependent. In this study, we aimed to elucidate the induction of PA-induced cell death associated with apoptosis activation. Therefore, 22 structurally different PAs were analyzed concerning the disturbance of cell viability in the metabolically competent human hepatoma cell line HepaRG. The chosen PAs represent the main necine base structures and the different esterification types. Open-chained and cyclic heliotridine- and retronecine-type diesters induced strong cytotoxic effects, while treatment of HepaRG with monoesters did not affect cell viability. For more detailed investigation of apoptosis induction, comprising caspase activation and gene expression analysis, 14 PA representatives were selected. The proapoptotic effects were in line with the potency observed in cell viability studies. In vitro data point towards a strong structure–activity relationship whose effectiveness needs to be investigated in vivo and can then be the basis for a structure-associated risk assessment.

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