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mitochondrial HBV X

H-R Lee, Y Y Cho, G Y Lee, D-G You, Y D Yoo, Y J Kim
Hepatitis B virus X protein (HBx) acts as a multifunctional protein that regulates intracellular signalling pathways during HBV infection. It has mainly been studied in terms of its interaction with cellular proteins. Here, we show that HBx induces membrane permeabilization independently of the mitochondrial permeability transition pore complex. We generated mitochondrial outer membrane-mimic liposomes to observe the direct effects of HBx on membranes. We found that HBx induced membrane permeabilization, and the region comprising the transmembrane domain and the mitochondrial-targeting sequence was sufficient for this process...
April 2018: Journal of Viral Hepatitis
Z I Siddiqui, S R Farooqui, S A Azam, M Afroz, S Wajid, S Parveen, S N Kazim
Hepatitis B virus (HBV) genomic mutations A1762T, G1764A and AG1762/1764TA cause production of HBV X protein (HBx) mutants, namely K130M, V131I and KV130/131MI. These mutations are important biomarkers for the development of cirrhosis and hepatocellular carcinoma (HCC) in chronic HBV patients. This study comparatively analyses the impact of intracellular expression of HBx mutants on HCC cell line Huh7. It was found that expression of KV130/131MI induced: cell proliferation, altered expression of cell cycle regulatory genes in favour of cell proliferation, intracellular reactive oxygen species (ROS) production and mitochondrial depolarization...
December 2017: Journal of Viral Hepatitis
H-C Chi, S-L Chen, S-L Lin, C-Y Tsai, W-Y Chuang, Y-H Lin, Y-H Huang, M-M Tsai, C-T Yeh, K-H Lin
Infection by hepatitis B virus (HBV) accounts for 50-80% of hepatocellular carcinoma (HCC) development worldwide, in which the HBV-encoded X protein (HBx) has critical role in the induction of carcinogenesis. Several studies have shown that thyroid hormone (TH) suppresses HCC development and protects hepatocytes from HBx-induced damage, thus it is of interest to examine whether TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice with or without TH, we confirmed the protective effects of TH on HBx-induced hepatocarcinogenesis, which was achieved via reduction of reactive oxygen species (ROS) inflicted DNA damage...
September 14, 2017: Oncogene
Ren Wang, Chen Yin, Xiao-Xing Li, Xian-Zi Yang, Yang Yang, Mei-Yin Zhang, Hui-Yun Wang, X F Steven Zheng
The development and progression of hepatocellular carcinoma (HCC) is accompanied with persistent oxidative stress, but the molecular basis is not well defined. Superoxide dismutase 2 (SOD2) is an important mitochondrial antioxidant and a key aging factor. Here we investigated the expression and clinical significance of SOD2 in a large cohort of HBV-positive HCC tumors. Both SOD2 mRNA and protein are reduced in human primary HCCs compared with matching liver tissues. Consistently, the SOD2 DNA copy numbers are decreased in HCCs, providing a genetic basis for the decrease in SOD2 mRNA expression...
June 2016: Aging
Lei Li, Hong-Hai Hong, Shi-Ping Chen, Cai-Qi Ma, Han-Yan Liu, Ya-Chao Yao
AIM: To investigate the anti-apoptotic capability of the hepatitis B virus (HBV) in the HepG2 hepatoma cell line and the underlying mechanisms. METHODS: Cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. Targeted knockdown of manganese superoxide dismutase (MnSOD), AMP-activated protein kinase (AMPK) and hepatitis B virus X protein (HBx) genes as well as AMPK agonist AICAR and antagonist compound C were employed to determine the correlations of expression of these genes...
May 7, 2016: World Journal of Gastroenterology: WJG
Ji-Hua Ren, Xiang Chen, Li Zhou, Na-Na Tao, Hong-Zhong Zhou, Bo Liu, Wan-Yu Li, Ai-Long Huang, Juan Chen
BACKGROUND/AIM: The hepatitis B virus (HBV) infection is accompanied by the induction of oxidative stress, especially mediated by HBV X protein (HBx). Oxidative stress has been implicated in a series of pathological states, such as DNA damage, cell survival and apoptosis. However, the host factor by which cells protect themselves under this oxidative stress is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we first confirmed that HBV infection significantly induced oxidative stress...
2016: PloS One
K Yuan, Y Lei, H-N Chen, Y Chen, T Zhang, K Li, N Xie, K Wang, X Feng, Q Pu, W Yang, M Wu, R Xiang, E C Nice, Y Wei, C Huang
Interleukin-6 (IL-6) has been demonstrated to be involved in Hepatitis B virus (HBV)-associated hepatocarcinogenesis through activation of the STAT3 pathway. The sustained activation of the IL-6/STAT3 pathway is frequently associated with repression of SOCS3, which is both a target gene and a negative regulator of STAT3. However, the silencing mechanism of SOCS3 in hepatocellular carcinoma (HCC) remains to be elucidated. Here, we showed that the repression of SOCS3 and sustained activation of IL-6/STAT3 pathway in HBV-producing HCC cells were caused by HBV-induced mitochondrial ROS accumulation...
April 2016: Cell Death and Differentiation
Dan Li, Zhixin Chen, Yun Chen, Na Lin, Xiaozhong Wang
OBJECTIVE: To identify the binding site position of the hepatitis B virus (HBV) X protein (HBx) functional interaction with the cytochrome C oxidase subunit III (COX III, a key regulator of mitochondrial function) by using a yeast two-hybrid system. METHODS: Two fragments of HBx mutants (X1 1-72aa and X2 1-117aa) were amplified by PCR and inserted into the bait plasmid pAS2-1.The resultant mutant plasmids were transfected into yeast cells using the lithium acetate-method...
October 2014: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Yun-li Wu, Dong Wang, Xian-e Peng, Yan-ling Chen, Da-li Zheng, Wan-nan Chen, Xu Lin
NAD(P)H:quinone oxidoreductase 1 (NQO1) is a phase II enzyme that participates in the detoxification of dopamine-derived quinone molecules and reactive oxygen species. Our prior work using a proteomic approach found that NQO1 protein levels were significantly decreased in stable hepatitis B virus (HBV)-producing hepatoma cells relative to the empty-vector-transfected controls. However, the mechanism and biological significance of the NQO1 suppression remain elusive. In this study we demonstrate that HBV X protein (HBx) induces epigenetic silencing of NQO1 in hepatoma cells through promoter hypermethylation via recruitment of DNA methyltransferase DNMT3A to the promoter region of the NQO1 gene...
December 2013: Free Radical Biology & Medicine
C Chakvetadze, F Bani-Sadr, F X Lescure, C Fontaine, C Le Pendeven, P Bonnard, P Mariot, P Soussan, G Pialoux
BACKGROUND: Hepatitis B reactivation has been observed in HIV-infected patients with isolated anti-HBc. However, the impact of isolated anti-HBc on liver fibrosis is not known in this population. METHODS: We investigated liver stiffness values (LSV) in a population of HIV-infected patients with isolated anti-HBc, and attempted to identify risk factors for high values. RESULTS: Fifty-one out of 69 patients (74%) had low LSV (≤7.1 kPa). In univariate analysis, high LSV (>7...
June 2013: Médecine et Maladies Infectieuses
Samuel Martín-Vílchez, Ricardo Moreno-Otero, Paloma Sanz-Cameno
The infection by hepatitis B virus often promotes chronic liver inflammation which progresses to cirrhosis and hepatocellular carcinoma in a high percentage of patients. The persistent activation of the immune system causes an incessant liver damage, which fosters a disorganized stimulation of tissue repair and remodelling phenomena. In turn, the viral protein X (HBx) is essential for virus replication and therefore for the maintenance of chronic infection. However, the important oncogenic potential of HBx seems to reside, on one hand, in its ability to integrate into cellular DNA and, additionally, in the transactivation of different cellular signaling pathways involved in cell growth regulation, apoptosis and DNA repair...
June 4, 2013: Medicina Clínica
Wei-Ping Lee, Keng-Hsin Lan, Chung-Pin Li, Yee Chao, Han-Chieh Lin, Shou-Dong Lee
The X protein of hepatitis B virus (HBx) has been specifically implicated in either pro-apoptotic or anti-apoptotic activity in an experimental system, but the underlying mechanism is yet uncertain. Activations of survival and proliferation signaling pathways appear to account partly for its anti-apoptotic property. Change in mitochondrial membrane potential may be responsible for its apoptotic property. In this study, we isolated two HBx isoforms from an HBV carrier, one of which contains Akt phosphorylation site at Ser31 and functions as an anti-apoptotic protein (designated HBx-S31)...
December 15, 2012: Archives of Biochemistry and Biophysics
Haiying Liu, Yanzhi Yuan, Hongyan Guo, Keith Mitchelson, Ke Zhang, Lan Xie, Wenyan Qin, Ying Lu, Jian Wang, Yong Guo, Yuxiang Zhou, Fuchu He
Hepatitis B virus (HBV) encoded X protein (HBx) has been implicated in apoptotic and related pathogenic events during hepatocellular carcinoma. However, the underlying molecular mechanism through which HBx acts is largely unclear. We used tandem affinity purification under mild conditions to gain insight into the HBx interactome in HBV-producing HepG2.2.15 cells and identified 49 proteins by mass spectrometry that are potentially associated with HBx. Two of the key proteins of the caspase-independent apoptosis pathway were newly identified, apoptosis-inducing factor (AIF) and the homologous AMID (AIF-homologue mitochondrion-associated inducer of death)...
October 5, 2012: Journal of Proteome Research
Chan-Yen Kuo, Ju-I Tsai, Tzu-Yu Chou, Man-Jung Hung, Cheng-Chung Wu, Shih-Lan Hsu, Guang-Yuh Hwang
The hepatitis B virus X protein (HBx) critically modulates cell growth by inducing apoptosis or proliferation. We sought to clarify whether HBx-mediated apoptosis in a CCL13 stable cell line (Chang-HBx) with inducible HBx expression proceeds through the extrinsic (death receptor-mediated) and/or intrinsic (mitochondrial-mediated) pathways of apoptosis. We used western blotting, cell viability assays, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, caspase activity assays, JC-1 staining and DNA fragmentation analysis to study the role of HBx in apoptosis...
July 2012: Oncology Reports
Weilin Wang, Dongkai Zhou, Jianfeng Wei, Zehui Wu, Xiaofei Cheng, Qiang Sun, Haiyang Xie, Lin Zhou, Shusen Zheng
The hepatitis B virus X (HBx) protein has many significant roles in hepatocellular carcinoma (HCC). Our previous research demonstrated that mitofusion-2 (Mfn2), a potential tumor suppressor gene in HCC, is a novel direct target of p53 that exerts apoptotic effects via the mitochondrial apoptotic pathway. However, the relationship between HBx and Mfn2 expression in the development of HCC is unknown. We found that HBx had little direct effect on the expression of Mfn2 or p53 in HCC cells not treated with doxorubicin...
May 4, 2012: Biochemical and Biophysical Research Communications
Jiejie Xu, Haiou Liu, Lin Chen, Shanshan Wang, Lei Zhou, Xiaojing Yun, Linlin Sun, Yumei Wen, Jianxin Gu
BACKGROUND & AIMS: Patients with chronic hepatitis B virus (HBV) infection are at risk for metastatic hepatocellular carcinoma (HCC). Metastatic cancer cells develop resistance to anoikis. The serine/threonine p21-activated kinase (PAK) 1 regulates cytoskeletal dynamics and protects cells from anoikis; it also promotes virus replication. We investigated the effects of PAK1 on anoikis resistance in human hepatoma cells and in mice. METHODS: We transfected human hepatoma cells with pHBV1...
July 2012: Gastroenterology
Bei Yang, Michael J Bouchard
Chronic hepatitis B virus (HBV) infections are associated with the development of hepatocellular carcinoma (HCC). The HBV X protein (HBx) is thought to play an important role in the development of HBV-associated HCC. One fundamental HBx function is elevation of cytosolic calcium signals; this HBx activity has been linked to HBx stimulation of cell proliferation and transcription pathways, as well as HBV replication. Exactly how HBx elevates cytosolic calcium signals is not clear. The studies described here show that HBx stimulates calcium entry into cells, resulting in an increased plateau level of inositol 1,4,5-triphosphate (IP3)-linked calcium signals...
January 2012: Journal of Virology
Yi Mao, Liang Da, Hong Tang, Jiali Yang, Yinrui Lei, Pierre Tiollais, Tsaiping Li, Mujun Zhao
The hepatitis B virus X protein (HBx) has been implicated in the development of hepatocellular carcinoma (HCC) associated with chronic infection. As a multifunctional protein, HBx regulates numerous cellular pathways, including autophagy. Although autophagy has been shown to participate in viral DNA replication and envelopment, it remains unclear whether HBx-activated autophagy affects host cell death, which is relevant to both viral pathogenicity and the development of HCC. Here, we showed that enforced expression of HBx can inhibit starvation-induced cell death in hepatic (L02 and Chang) or hepatoma (HepG2 and BEL-7404) cell lines...
November 11, 2011: Biochemical and Biophysical Research Communications
Samuel Martin-Vilchez, Enrique Lara-Pezzi, Maria Trapero-Marugán, Ricardo Moreno-Otero, Paloma Sanz-Cameno
Hepatitis B virus is considered one of the most significant environmental carcinogens in humans. Because the mechanisms of HBV replication and the development of hepatocellular carcinoma (HCC) are partially known, HBV-associated pathogenesis remains a challenge to increase its understanding. Evidence suggests that the regulatory protein hepatitis B virus X (HBx) mediates the establishment and maintenance of the chronic carrier state. HBx is a multifunctional and potentially oncogenic protein that is conserved among mammalian hepadnaviruses; it is produced very early after infection and throughout the chronic phase...
September 2011: Reviews in Medical Virology
Qi Ling, Xiao Xu, Xuyong Wei, Weibing Wang, Bin Zhou, Bei Wang, Shusen Zheng
BACKGROUND: Oxymatrine, an isolated extract from traditional Chinese herb Sophora Flavescens Ait, has been traditionally used for therapy of anti-hepatitis B virus, anti-inflammation and anti-anaphylaxis. The present study was to investigate the anti-cancer effect of oxymatrine on human pancreatic cancer PANC-1 cells, and its possible molecular mechanism. METHODS: The effect of oxymatrine on the viability and apoptosis was examined by methyl thiazolyl tetrazolium and flow cytometry analysis...
June 29, 2011: Journal of Experimental & Clinical Cancer Research: CR
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