Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four fibrolamellar liver carcinomas were surgically removed and were postoperatively examined. Three patients are alive roughly three years from surgery, and there are no signs of imminent recurrence, while the fourth case was diagnosed only two months back. The carcinomas had developed in non-cirrhotic livers which also produced negative responses to serological tests for hepatitis B. In flow cytometry, DNA indices were indicative of diploidy in two cases and aneuploidy in the other two. The highest DNA index value was recorded from the smallest tumour which could be assigned to the category of "minute HCC". No correlation was found to exist either between age, sex, and DNA index. Positive CEA reaction was immunohistochemically recorded from few tumour cells, whereas negative AFP responses were exhibited by all four tumours. Appearance of AAT in tumour cells was detected in three cases. High degree of differentiation, similarity between tumour and liver cells, and oncocytoid nature of cells were revealed by optical light and electron microscopy. This high degree of differentiation was additionally confirmed by two factors: glucose-6-phosphatase activity was preserved in all four tumours, adenosinetriphosphatase activity was histochemically detectable from certain points of the tumour cell membrane. Gamma-glutamyl-transpeptidase activity, too, was very strongly pronounced in all tumour cells, which, however, cannot be interpreted as a sign of differentiation. Membrane-bordered "dense-core" granules were visible in few tumour cells in two cases. Intensive granular serotonin reactions were immunohistochemically recorded from the majority of tumour cells in the same cases. Our histochemical and ultrastructural parameters have produced clear-cut evidence to the hepatocyte nature of FLC cells. Yet, the presence of secretory granules and positive serotonin reaction might possibly support the assumption that the FLC originates from those pluripotent cells of the liver which may develop in two directions, depending on the individual case, to become either hepatocytes or neurosecretory cells.
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PMID:[Fibrolamellar liver carcinoma]. 215 93

PLC/PRF/5, a tissue culture cell line derived from a human hepatocellular carcinoma and producing hepatitis B surface antigen (HBsAg), was studied by immune and enzyme histochemical techniques. HBsAg was demonstrated in the cytoplasm and on the surface of tumor cells. The percentage of HBsAg-positive cells in subculture increased with time until almost all cells expressed HBsAg when the monolayer reached confluence. Similar patterns were found for alpha 1-anti-trypsin and carcino-embryonic antigen, whereas alpha-fetoprotein was observed only in small foci of cells. Hepatitis B core antigen and albumin were not detected. gamma-Glutamyl transferase activity was markedly increased in the tumor cells, whereas adenosine triphosphatase and glucose-6-phosphatase activities were not demonstrable. Patterns of antigenic expression and enzyme phenotype of PLC/PRF/5 cells show remarkable resemblance to those observed in vivo in human hepatocellular carcinoma. Therefore, this cell line may be a useful model to study the control and modulation of both oncofetal antigens and HBsAg.
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PMID:Immune and enzyme histochemical studies of a human hepatocellular carcinoma cell line producing hepatitis B surface antigen. 616 57

The complete hepatitis B virus (Dane particle) contains a circular doublestranded DNA with single stranded regions and an endogenous DNA polymerase. The HBV associated DNA polymerase closes the single stranded regions of the HBV-DNA in the presence of triphosphatase and a detergent. The DNA polymerase reaction can be inhibition by antiviral substances that exhibit different mode of actions: intercalating agents, phosphonoformiate and the triphosphates of arabinofuranosyladenine and arabinofuranosylcytosine. The value of these in vitro test for the therapy of HBsAg positive chronic liver disease is limited by the fact that is remains so far unclear whether the HBV associated DNA polymerase is a virus- or a host-coded enzyme, and whether virus- or host-coded enzymes are involved in HBV-DNA synthesis in vivo.
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PMID:[Inhibition of hepatitis B virus associated DNA polymerase by antiviral agents: in vitro studies with clinical implications (author's transl)]. 645 51

The X protein (pX) of hepatitis B virus (HBV) is a general transcription regulator and directly associated with the transcription machinery. pX cannot bind DNA directly but interacts with cellular factors that bind the regulatory elements. There is an accumulation of evidence concerning different activities exerted by pX in transfected cells; nevertheless, the function and the biochemical properties of the protein are unknown. Biochemical analysis of bacterially expressed pX revealed that the protein possesses hydrolytic activity specific for adenine nucleotides with a Km of approximately 95 microM. This ATPase (dATPase) activity is not DNA-dependent. Mutation analysis revealed that the 88-119 amino-acid region of pX is required for its maximal activity. The putative involvement of (d)ATPase activity in the mechanism of transcription stimulation exerted by pX may be proposed by a certain analogy to the activity of transcription factors which participate in the initiation complex.
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PMID:The X protein of hepatitis B virus has a ribo/deoxy ATPase activity. 800 50

The feasibility of liver repopulation with hepatocytes has been shown, although clinical applications demand significant hepatic replacement. To show whether portal vascular bed in large animals could accomodate a greater cell number, we analyzed liver repopulation in syngeneic Fischer 344 rats deficient in dipeptidyl peptidase IV. This system allowed localization of transplanted normal hepatocytes in liver or various ectopic sites, as well as dual studies for analysis of gene expression. Interestingly, the product of a dipeptidyl peptidase IV substrate inactivated bile canalicular adenosine triphosphatase (ATPase) activity in normal but not in dipeptidyl peptidase IV-deficient rats, which allowed localization of dipeptidyl peptidase IV-deficient hepatocytes in normal rat liver for additional reversed transplantation systems. Further studies with genetically marked cells showed that because of the size difference between hepatocytes and portal vein radicles, intrasplenically transplanted cells were distributed in periportal areas (zone 1) in mice, whereas in larger animals (rats or rabbits) cells were also distributed downstream to midlobular (zone 2) or perivenous (zone 3) areas. Transplantation of an escalating number of hepatocytes showed that adult rats tolerated intrasplenic injection of a large cell number in single sessions (up to 1 X 10(8), approximately 10% to 15% of the host hepatocyte mass). Morphometric analysis of recipient livers showed survival of a significantly greater cell number with incorporation in host liver plates. At 4 weeks, transplantation of 2 x 10(7) hepatocytes into adult rats led to a survival of 1.4 +/- 1.0 x 10(6) transplanted cells/cm3 liver, whereas after transplantation of 5 x 10(7) cells or 7.5 x 10(7) cells, the number of surviving transplanted cells in the liver significantly increased to 4.1 +/- 1.4 x 10(6) transplanted cells/cm3 liver (mean, 2.9-fold; P<.003) and 5.5 +/- 1.3 x 10(6) transplanted cells/cm3 liver (mean, 3.9-fold; P<.003), respectively. When cells were injected in greater numbers, transplanted hepatocytes retained normal function and produced more serum albumin or hepatitis B surface antigen in deficient hosts. These data indicate the feasibility in larger animals of significant liver repopulation with hepatocyte transplantation. Use of dipeptidyl peptidase IV-deficient rats should help further analysis of mechanisms in liver repopulation.
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PMID:Studies of liver repopulation using the dipeptidyl peptidase IV-deficient rat and other rodent recipients: cell size and structure relationships regulate capacity for increased transplanted hepatocyte mass in the liver lobule. 861 28

COS7 cells and other cell lines expressing the SV40 large T-antigen, have been of great benefit in transfection studies using transient expression vectors which contain the SV40 origin of replication, as these cells allow plasmid replication to a high copy number. As no T-antigen expressing cell line derived from a well characterised hepatocyte-like continuous cell line currently exists, the establishment of such a cell line for studies which require expression of hepatocyte-specific factors would be extremely useful. A HepG2-derived stable cell line (THT1) was therefore developed which demonstrates a high level of transfection efficiency whilst retaining hepatocyte-like features, such as the production of hepatitis B virus. The THT1 cell line displayed chromosomal integration of the SV40 T-antigen gene and nuclear expression of the antigen. The cell line also maintained the general morphological features of its parent cell line, and showed an increased rate of cell growth.
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PMID:The development and characterisation of a SV40 T-antigen positive cell line of human hepatic origin. 912 63

Hepatitis B virus (HBV) has a unique fourth open reading frame coding for a 16.5-kDa protein known as hepatitis B virus X protein (HBX). The importance of HBX in the life cycle of HBV has been well established, but the underlying molecular function of HBX remains controversial. We previously identified a proteasome subunit PSMA7 that interacts specifically with HBX in the Saccharomyces cerevisiae two-hybrid system. Here we demonstrate that PSMC1, an ATPase-like subunit of the 19 S proteasome component, also interacts with HBX and PSMA7. Analysis of the interacting domains among PSMA7, PSMC1, and HBX by deletion and site-directed mutagenesis suggested a mutually competitive structural relationship among these polypeptides. The competitive nature of these interactions is further demonstrated using a modified yeast two-hybrid dissociator system. The crucial HBX sequences involved in interaction with PSMA7 and PSMC1 are important for its function as a transcriptional coactivator. HBX, while functioning as a coactivator of AP-1 and acidic activator VP-16 in mammalian cells, had no effect on the transactivation function of their functional orthologs GCN4 and Gal4 in yeast. Overexpression of PSMC1 seemed to suppress the expression of various reporters in mammalian cells; this effect, however, was overcome by coexpression of HBX. In addition, HBX expression inhibited the cellular turnover of c-Jun and ubiquitin-Arg-beta-galactosidase, two well known substrates of the ubiquitin-proteasome pathway. Thus, interaction of HBX with the proteasome complex in metazoan cells may underlie the functional basis of proteasome as a cellular target of HBX.
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PMID:Structural and functional characterization of interaction between hepatitis B virus X protein and the proteasome complex. 1074 18

We have used the Hepatitis B Virus DNA genome as a probe to identify genes clonally mutated in vivo, in human liver cancers. In a tumor, HBV-DNA was found to be integrated into the gene encoding Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA), which pumps calcium, an important intracellular messenger for cell viability and growth, from the cytosol to the endoplasmic reticulum. The HBV X gene promoter cis-activates chimeric HBV X/SERCA1 transcripts, with splicing of SERCA1 exon 11, encoding C-terminally truncated SERCA1 proteins. Two chimeric HBV X/SERCA1 proteins accumulate in the tumor and form dimers. In vitro analyses have demonstrated that these proteins localize to the ER, determine its calcium depletion and induce cell death. We have also shown that these biological effects are related to expression of the SERCA, rather than of the viral moiety. This report involves for the first time the expression of mutated SERCA proteins in vivo in a tumor cell proliferation and in vitro in the control of cell viability. Oncogene (2000).
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PMID:Hepatitis B virus-related insertional mutagenesis implicates SERCA1 gene in the control of apoptosis. 1087 38

Initiation of reverse transcription in hepadnaviruses (hepatitis B viruses) depends on the specific binding of an RNA signal (the packaging signal, epsilon) on the pregenomic RNA template by the viral reverse transcriptase (RT) and is primed by the RT itself (protein priming). We have previously shown that the RT-epsilon interaction and protein priming require the cellular heat shock protein, Hsp90. However, additional host factors required for these reactions remained to be identified. We now report that five cellular chaperone proteins, all known cofactors of Hsp90, were sufficient to reconstitute a duck hepatitis B virus RT active in epsilon binding and protein priming in vitro. Four proteins, Hsp90, Hsp70, Hsp40, and Hop, were required for reconstitution of RT activity, and the fifth protein, p23, further enhanced the kinetics of reconstitution. RT activation by the chaperone proteins is a dynamic process dependent on ATP hydrolysis and the Hsp90 ATPase activity. Thus, our results have defined a minimal complement of host factors necessary and sufficient for RT activation. Furthermore, this defined in vitro reconstitution system has now paved the way for future biochemical and structural studies to elucidate the mechanisms of RT activation and chaperone functions.
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PMID:In vitro reconstitution of functional hepadnavirus reverse transcriptase with cellular chaperone proteins. 1173 92

The hepatitis B virus X protein (HBx) is a multifunctional protein, acting on different targets (e.g. transcription factors, cytoplasmic kinases, and mitochondrial proteins) and exerting cellular effects as diverse as stimulation of cell proliferation and apoptosis. In its biological effects, the modulation of cellular Ca2+ signals has been proposed to be involved, but the direct assessment of Ca2+ homeostasis in HBx-transfected cells has not been carried out yet. In this work, we have employed for this purpose aequorin-based recombinant probes specifically targeted to intracellular organelles and microdomains. Using these probes, we observed that overexpression of HBx enhanced agonist-evoked cytosolic Ca2+ signals in HepG2 and HeLa cells, without affecting either the steady state of endoplasmic reticulum Ca2+ concentration or the kinetics of Ca2+ release. Rather, caspase-3-dependent cleavage of the plasma membrane Ca2+ ATPase could be demonstrated, and larger rises were detected in the cytoplasmic rim beneath the plasma membrane. In mitochondria, major morphological (fragmentation and swelling) and functional (reduced Ca2+ uptake) alterations were detected in HBx-expressing cells. As to the cellular consequences, we observed that HBx-induced apoptosis was markedly reduced when the alterations in Ca2+ signaling (e.g. by loading a Ca2+ chelator or preventing PMCA cleavage) or the downstream effects (e.g. by inhibiting mitochondrial permeability transition) were prevented. Overall, these results indicate that HBx perturbs intracellular Ca2+ homeostasis, acting on the extrusion mechanisms, and that this effect plays an important role in the control of HBx-related apoptosis.
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PMID:Caspase-dependent alterations of Ca2+ signaling in the induction of apoptosis by hepatitis B virus X protein. 1279 72


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