A proteomics analysis of cellular proteins associated with HBV genotype-specific HBX: potential in identification of early diagnostic markers for HCC

Tan, Tuan Lin; Chen, Wei Ning

doi:10.1016/j.jcv.2004.12.015

Cited by 37 publications

(32 citation statements)

References 22 publications

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“…Recent studies suggest that time to HBeAg seroconversion, HBV DNA levels, prevalence of double mutation in the core promoter (CP, at nucleotides 1762T/1764A), in the precore (PC) region (at nucleotide 1896A) can influence the disease progression and are also associated with HBV genotypes [2,7,8] . Very recently, it was shown that HBV genotypes can influence the cellular response [9] , hepatocarcinogenic mechanisms [10] and even the effect of same mutations are genotype differentiated [11] .…”

Section: Introductionmentioning

confidence: 99%

Molecular Epidemiology and Clinical Significance of Hepatitis B Virus Genotypes, Core Promoter and Precore Mutations in Eastern India

Datta

Biswas²,

Chandra³

et al. 2008

Intervirology

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Objectives: This unmatched case-control study aimed at determining the molecular epidemiology and clinical significance of HBV genotypes, core promoter (CP) and precore (PC) mutations in Eastern India. Methods: Serological, biochemical and molecular assays were used to examine antigens, ALT, genotypes, mutations and viremia among 106 inactive carriers and 183 chronic liver disease (CLD) patients. Results: Male gender (p < 0.001), HBeAg positivity (p = 0.050), high ALT (p < 0.001), high viremia (p < 0.001), CP mutations (p < 0.001), and genotypes A (p < 0.001) and C (p = 0.027) were significantly associated with CLD. Subjects infected with genotypes A and C had significantly higher prevalence of BCP mutations (p < 0.001), and low incidence of PC mutation (p < 0.001 and p = 0.047, respectively). Prevalence of genotype D was significantly higher among subjects with history of familial/childhood jaundice, while genotypes A and C were frequent among subjects with possible percutaneous exposure. Conclusions: Significant differences in risk factors and disease manifestation do exist among patients infected with different HBV genotypes. Genotypes A and C are frequently found among chronic liver disease patients, while genotype D is associated with inactive HBeAg-negative infections. This evaluation of clinical relevance of HBV genotypes, mutations and risk factors may be useful in disease prognosis, management and prevention strategies.

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Section: Introductionmentioning

confidence: 99%

Molecular Epidemiology and Clinical Significance of Hepatitis B Virus Genotypes, Core Promoter and Precore Mutations in Eastern India

Datta

Biswas²,

Chandra³

et al. 2008

Intervirology

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“…It will be of great interest to detect changes in quantitative protein profiles and to infer biological function from the observed patterns. Proteomics analysis has been widely used to establish cellular signaling pathways in response to various external stimuli, including comparing normal and diseased conditions (15)(16)(17)(18). Established methods for relative quantitation of proteins involve isotope-coded affinity tag (19) and chemical and enzymatic modifications (20).…”

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confidence: 99%

Comparative Proteomics Analysis of Vascular Smooth Muscle Cells Incubated with S- and R-Enantiomers of Atenolol Using iTRAQ-coupled Two-dimensional LC-MS/MS

Sui¹,

Zhang²,

Tan

et al. 2008

Molecular & Cellular Proteomics

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Atenolol is a ␤ 1 -selective drug, which exerts greater blocking activity on ␤ 1 -adrenoreceptors than on ␤ 2 -adrenoreceptors, with the S-enantiomer being more active than R-enantiomer. The aim of this study was to investigate the proteins with differential protein expression levels in the proteome of vascular smooth muscle cells (A7r5) incubated separately with individual enantiomers of atenolol using an iTRAQ-coupled two-dimensional LC-MS/MS approach. Our results indicated that some calcium-binding proteins such as calmodulin, protein S100-A11, protein S100-A4, and annexin A6 were downregulated and showed relatively lower protein levels in cells incubated with the S-enantiomer of atenolol than those incubated with the R-enantiomer, whereas metabolic enzymes such as aspartate aminotransferase, glutathione S-transferase P, NADH-cytochrome b 5 reductase, and ␣-N-acetylgalactosaminidase precursor were up-regulated and displayed higher protein levels in cells incubated with the S-enantiomer relative to those incubated with the R-enantiomer. The involvement of NADHcytochrome b 5 reductase in the intracellular anabolic activity was validated by NAD ؉ /NADH assay with a higher ratio of NAD ؉ /NADH correlating with a higher proportion of NAD ؉ . The down-regulation of the calciumbinding proteins was possibly involved in the lower intracellular Ca 2؉ The ␤-adrenoreceptors belong to the family of G proteincoupled receptors (GPRs) 1 (1) characterized by seven transmembrane-spanning domains forming a pocket in which the agonists and competitive antagonists find their binding sites (2). The signal transduction process triggered by agonist binding to ␤-adrenoreceptors consists of discrete steps, and one of the earliest is the coupling of this complex to heterotrimeric G protein that dissociates in G␣ and G␤␥ subunits (3). G␣ and G␤␥ subunits activate or inhibit a number of effector enzymes such as adenylyl cyclase, phospholipase C, ion channels, or mitogen-activated protein kinases (MAPKs), resulting in a variety of cellular functions. One of the well documented signal transduction steps is that the coupling of this complex to the heterotrimeric G protein G␣ subunits will stimulate adenylyl cyclase activity, which produces the second messenger cAMP. Protein kinase A activated by cAMP phosphorylates L-type calcium channels and myosin light chain kinase (4, 5), facilitating Ca 2ϩ entry and producing the positive inotropic effect in atria and ventricles. In addition to mechanisms that indirectly lead to alterations in ion transport, ␤-adrenoreceptor activation is more directly linked to ion channels (6). After agonist stimulation, most GPRs rapidly lose their ability to respond to agonist. For many GPRs, this process, commonly referred to as desensitization, appears to be primarily mediated by two protein families: G protein-coupled receptor kinases (GRKs) and arrestins. GRKs specifically bind to the agonist-occupied receptor, thereby promoting receptor phosphorylation, which in turn leads to arrestin binding. Arrestin bin...

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“…A number of studies have reported that a frequently occurring HBx mutation is the deletion of the COOH-terminus in tissue samples of patients with HCC [3][4][5] . These data suggest that COOH-terminal truncations of HBx may play a critical role in hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…As such, HBx is involved in the regulation of genotoxic stress responses, protein degradation pathways, cell proliferation and apoptosis, immune responses and cell adhesion [2] . It has been reported that COOH-terminal deletions of HBx are frequent events in HBV-associated HCC tissues [3][4][5] . In addition, our previous study found a natural mutant of HBx that had 27 truncated amino acids at the COOH-terminal (termed HBxΔ127) [6] , which was consistent with other reports [3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

“…It has been reported that COOH-terminal deletions of HBx are frequent events in HBV-associated HCC tissues [3][4][5] . In addition, our previous study found a natural mutant of HBx that had 27 truncated amino acids at the COOH-terminal (termed HBxΔ127) [6] , which was consistent with other reports [3][4][5] . It has been reported that HBx mutants with the COOH-terminal deletion abrogated the antiproliferative effects of wild type HBx [7] .…”

Section: Introductionmentioning

confidence: 99%

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A mutant of HBx (HBxΔ127) promotes hepatoma cell growth via sterol regulatory element binding protein 1c involving 5-lipoxygenase

Wang

Zhang

et al. 2010

Acta Pharmacol Sin

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Aim: Previously, we identified a natural mutant of hepatitis B virus X gene (HBx) with a deletion from 382 to 401 base pairs (termed HBxΔ127), which could potently enhance growth of hepatoma cells. In this study, we further investigated the mechanism of increased hepatoma cell growth that was mediated by HBxΔ127. Methods: We examined the effect of HBxΔ127 on the transcription factor sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS) in a model of HepG2-XΔ127 (or H7402-XΔ127) cells, which was stably transfected with HBxΔ127 gene in a human hepatoma HepG2 (or H7402) cell line. Results: Relative to wild type HBx, HBxΔ127 was able to potently activate SREBP-1c at the levels of promoter activity, mRNA and protein by a luciferase reporter gene assay, RT-PCR and Western blot analysis. Then, using the treatment with MK886, a specific 5-lipoxygenases (5-LOX) inhibitor, (or 5-LOX siRNA) we identified that 5-LOX was responsible for the upregulation of SREBP-1c by luciferase reporter gene assay, RT-PCR and Western blot analysis. Because FAS was a target gene of SREBP-1c, we further showed that HBxΔ127 was able to strongly activate the promoter activity of FAS and upregulated the mRNA expression level of FAS as well, by luciferase reporter gene assay and RT-PCR. In function, flow cytometry analysis revealed that FAS contributed to the growth of hepatoma cells that was mediated by HBxΔ127, using cerulenin (a FAS inhibitor). Conclusion: HBxΔ127 promotes hepatoma cell growth through activating SREBP-1c involving 5-LOX.

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A proteomics analysis of cellular proteins associated with HBV genotype-specific HBX: potential in identification of early diagnostic markers for HCC

Cited by 37 publications

References 22 publications

Molecular Epidemiology and Clinical Significance of Hepatitis B Virus Genotypes, Core Promoter and Precore Mutations in Eastern India

Molecular Epidemiology and Clinical Significance of Hepatitis B Virus Genotypes, Core Promoter and Precore Mutations in Eastern India

Comparative Proteomics Analysis of Vascular Smooth Muscle Cells Incubated with S- and R-Enantiomers of Atenolol Using iTRAQ-coupled Two-dimensional LC-MS/MS

A mutant of HBx (HBxΔ127) promotes hepatoma cell growth via sterol regulatory element binding protein 1c involving 5-lipoxygenase

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