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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human angiotensinogen gene consists of five exons interrupted by four introns and spans 12 kilobases. The gene is expressed in liver and HepG2 cells derived from human hepatoma. To examine whether the angiotensinogen gene is expressed in extrahepatic cells, RNAs from kidney and several human cell lines have been isolated and analyzed by Northern blot hybridization with the cloned gene as a probe. The mRNA for angiotensinogen was detected in human kidney and human glioblastoma (A-172) cells. To investigate the endogenous regulation of angiotensinogen gene expression, HepG2 cells were cultured in the presence of 3-aminobenzamide, a specific inhibitor of poly(ADP-ribose) polymerase. The expression of the angiotensinogen gene was demonstrated to be completely suppressed by 3-aminobenzamide (10 mM).
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PMID:Expression of the human angiotensinogen gene in human cell lines. 170 21

The cellular mechanism by which the angiotensin II (AII) agonist, Sar1-AII, inhibits production and release of angiotensinogen in human hepatoma HepG2 cells was examined. Pretreatment of HepG2 cells with pertussis toxin attenuated the ability of Sar1-AII to block angiotensinogen production. This effect could be correlated with the in situ ADP-ribosylation of a protein(s) of apparent molecular weight 39,000-41,000 on SDS-PAGE, and attenuation of the ability of Sar1-AII to inhibit cAMP accumulation. The role of cAMP in angiotensinogen production was examined. A transient increase in cAMP accumulation above basal could be evoked by forskolin (8-fold) or by glucagon (5-fold) using insulin-deficient media. Although neither forskolin nor glucagon had a significant effect on angiotensinogen production agents producing a sustained increase in intracellular cAMP (8-bromo-cAMP, dibutyryl-cAMP, cholera toxin) were able to increase angiotensinogen production. Although these data indicate that intracellular cAMP is a regulatory factor in angiotensinogen production other evidence suggests that modulation of intracellular cAMP is not entirely responsible for the effects of Sar1-AII.
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PMID:Involvement of a pertussis toxin-sensitive G protein in the regulation of angiotensinogen production by an angiotensin II analog in HepG2 cells. 217 1

To investigate whether glucocorticoids can stimulate rat brain angiotensinogen production directly, we have studied the effect of dexamethasone on angiotensinogen secretion and angiotensinogen mRNA concentration in primary astroglial cultures from rat diencephalon. Dexamethasone stimulated angiotensinogen secretion by astroglial cells in a dose-related fashion. The half-maximally effective concentration was 11 nM, and the effect was blocked by RU 486, an antagonist of type II glucocorticoid receptors. This was similar to what was observed in rat hepatoma H4IIEC cells, where the half-maximally effective concentration of dexamethasone on angiotensinogen secretion was 10 nM. At maximal concentrations, dexamethasone increased angiotensinogen secretion and angiotensinogen mRNA concentration 2-fold in astroglial cells. In the hepatoma cells, however, the increase in angiotensinogen secretion was 5-fold. The in vivo diencephalon angiotensinogen mRNA concentration was decreased after adrenalectomy. Dexamethasone restored those levels to normal and induced a modest increase when the animals were killed 6 h after drug administration. In contrast, dexamethasone induced a robust increase in liver angiotensinogen mRNA concentration in the same animals. These results indicate that glucocorticoids increase angiotensinogen production through a direct receptor-mediated mechanism in both liver and brain. However, the angiotensinogen gene appears much more responsive to the action of glucocorticoids in liver than in brain.
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PMID:Glucocorticoid regulation of rat diencephalon angiotensinogen production. 229 77

The acute-phase activation of the rat angiotensinogen (rAT) gene in liver cells is a transcriptional event mediated through an interleukin-1-inducible, NF kappa B-binding, cis-acting element (the acute-phase response element [APRE]). Using a cell culture model for the acute-phase response, we showed that the increase in angiotensionogen mRNA in H35 rat hepatoma cells requires costimulation with glucocorticoids and cytokines. Stably transfected rAT promoter-luciferase reporter genes were also activated by cytokines only in the presence of glucocorticoids. This permissive role of glucocorticoids is dependent on the expression of functional glucocorticoid receptors, because in HepG2 cells naturally deficient in such receptors, rAT gene-luciferase reporter constructs responded to interleukin-1 only when cotransfected with an expression vector for the glucocorticoid receptor. Point mutations in the two rAT gene glucocorticoid response elements located adjacent to the APRE led to loss of interleukin-1 inducibility. Induction of luciferase activity in transfected cells occurred even in the presence of cycloheximide, demonstrating that this synergistic response did not depend on new protein synthesis. Thus, a direct interaction between the interleukin-1-inducible NF kappa B-binding APRE and glucocorticoid response elements, located in cis, underlies the acute-phase activation of the rAT gene.
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PMID:The permissive role of glucocorticoids on interleukin-1 stimulation of angiotensinogen gene transcription is mediated by an interaction between inducible enhancers. 237 Aug 71

Three South African blacks with hepatocellular carcinoma and arterial hypertension are described. Plasma angiotensinogen (renin substrate) concentrations were increased eightfold to 10-fold in the two patients in whom these concentrations were measured. One of these two patients also showed a 34-fold rise in plasma inactive, active, and total renin concentrations, and an elevated plasma renin activity (2.73 ng.L-1.s-1 angiotensin l/mL/h). Inactive renin (prorenin) constituted 90% of the total plasma renin concentration. In the third patient only plasma renin activity was measured, and this was considerably raised (6.05 ng.L-1.s-1; angiotensin l/mL/h). Thus, the arterial hypertension that rarely complicates hepatocellular carcinoma may be caused either by a combination of eutopic synthesis of excessive quantities of angiotensinogen and ectopic production and secretion of active renin by malignant hepatocytes, or by eutopic production of angiotensinogen alone.
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PMID:Arterial hypertension as a paraneoplastic phenomenon in hepatocellular carcinoma. 254 97

The aim of this study was to examine in Hep G2, a human hepatoma-derived cell line, the presence of angiotensin II (ANG II) receptors and the effect of ANG II and its analogues on angiotensinogen production. The presence of ANG II receptors was demonstrated using a long-acting ANG II analogue, 125I-labeled [Sar1]ANG II. A single class of specific binding sites was identified in these cells with a dissociation constant (Kd) of 2 nM. The number and affinity of these binding sites were not changed by [Sar1]ANG II treatment over 24 h. ANG II showed an inhibitory effect on angiotensinogen production. [Sar1]ANG II also exhibited a similar inhibitory effect as that of ANG II but to a greater extent and therefore was used throughout these studies. [Sar1]ANG II inhibited angiotensinogen production in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) of 2 nM. Other ANG II analogues showed similar effects on angiotensinogen production. In order of decreasing ability, they were [Sar1]ANG II greater than [Sar1-Ala8]ANG II greater than [Sar1-Val8]ANG II greater than [Sar1-Val5-(Br5)-Phe8]ANG II greater than [Sar1-Val5-DPhe8]ANG II. Results of these studies show that the Hep G2 cell possesses specific ANG II receptors and that [Sar1]ANG II induces a dose-dependent inhibition of angiotensinogen production in this system.
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PMID:Inhibition of angiotensinogen production by angiotensin II analogues in human hepatoma cell line. 259 83

Angiotensinogen has been identified as one of the acute-phase reactants. In vitro studies were carried out using the Reuber H35 hepatoma cell line to identify the species of cytokines contributing to the increased synthesis of angiotensinogen in the liver. Angiotensinogen secretion by H35 cells was maximally increased 4-fold by the addition of 10(-7) M dexamethasone. Under this condition, angiotensinogen secretion was further stimulated by B cell stimulatory factor 2/interleukin-6 (IL-6, 50 U/ml), but not by interleukin-1 or interferon-alpha. In the absence of glucocorticoid, IL-6 did not affect angiotensinogen secretion by H35 cells, indicating that the presence of glucocorticoid is required for the stimulatory activity of IL-6. These results suggest that IL-6 is a mediator responsible for the increased synthesis of angiotensinogen in the liver during acute inflammation.
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PMID:Angiotensinogen production by rat hepatoma cells is stimulated by B cell stimulatory factor 2/interleukin-6. 278 93

Angiotensinogen is the precursor of biologically active peptide angiotensin II and its synthesis is increased in the liver during acute inflammation. We have used radiolabeled human angiotensinogen cDNA to study the effect of hepatocyte stimulating factor (HSF), a protein synthesized in differentiating monocytes which increases the synthesis of various hepatic proteins during inflammation, on angiotensinogen mRNA levels in human hepatoma cells (HepG2). Our results indicate that angiotensinogen mRNA is present in human hepatoma (HepG2) cells and its levels are decreased when treated with hepatocyte stimulating factor. Although dexamethasone elevated angiotensinogen mRNA levels, HSF reduced this increase. These results suggest that a factor other than HSF may be involved in elevating the angiotensinogen mRNA levels in the liver during inflammation.
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PMID:Regulation of angiotensinogen gene expression in a human hepatoma cell line. 282 52

To define the basis of the heterogeneity of angiotensinogen, we have characterized the immunoreactivity of high molecular weight (HMW) and low molecular weight (LMW) plasma angiotensinogen, the angiotensinogen precursor synthesized by cell-free translation, and angiotensinogen secreted by human hepatoma (Hep G2) cells. Angiotensinogen precursor synthesized by rabbit reticulocyte lysate primed with RNA prepared from liver or Hep G2 cells was compared with angiotensinogen secreted by Hep G2 cells by using immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). So as to assess the contribution of N-glycosylation of angiotensinogen, Hep G2 cells were incubated in the presence of tunicamycin. Glycosylation of secreted angiotensinogen was further characterized by using chromatography on concanavalin A-Sepharose, digestion with neuraminidase, and treatment with trifluoromethane sulfonic acid. In Sephadex G-200 column chromatography, HMW plasma angiotensinogen eluted just after the column void volume and was clearly separated from LMW angiotensinogen which eluted just before bovine serum albumin. Both HMW and LMW plasma angiotensinogen were shown to bind to monoclonal and polyclonal antibodies raised against pure LMW angiotensinogen. Only one angiotensinogen precursor (mol wt 50,000) was identified by cell-free translation which, after cleavage by renin, was reduced to mol wt 45,600. Angiotensinogen secreted by Hep G2 cells showed electrophoretic heterogeneity (mol wt 53,100-65,400). Tunicamycin-treated Hep G2 cells secreted five discrete forms of angiotensinogen, a predominant form of mol wt 46,200, with other forms (mol wt 46,800, 48,100, 49,200, and 49,600) representing 10% of secreted angiotensinogen. All five forms showed a similar reduction in molecular weight after cleavage by renin. The predominant 46,200-mol wt protein represented nonglycosylated angiotensinogen in that, after cleavage by renin, it had an electrophoretic mobility (mol wt 45,600) identical to the desangiotensin I-angiotensinogen resulting from renin cleavage of the angiotensinogen precursor. The other higher molecular weight forms of angiotensinogen secreted by tunicamycin-treated Hep G2 cells were shown to represent O-glycosylated angiotensinogen in that they were reduced to 46,200 mol wt by treatment with trifluoromethane sulfonic acid. Dexamethasone (10(-7) and 10(-6)M) stimulated angiotensinogen secretion by Hep G2 cells two- to fourfold, both in the absence and presence of tunicamycin. However, a small stimulatory effect of mestranol (10(-7) M) was evident only in the presence of tunicamycin. Neither dexamethasone nor mestranol influenced the electrophoretic pattern (SDS-PAGE) of angiotensinogen secreted by Hep G2 cells. However, when incubation media were chromatographed on Sephadex G-200 with subsequent immunoprecipitation of the column fractions, both dexamethasone and mestranol were shown to stimulate the secretion of HMW angiotensinogen (eluting just after the column void volume) which, on SDS-PAGE, migrated in a position identical to LMW angiotensinogen. From these studies, we conclude that all forms of human angiotensinogen are derived from a single precursor. The heterogeneity of secreted angiotensinogen represents differences in posttranslational processing of angiotensinogen. This processing includes both N- and O-glycosylation, and also the formation of HMW complexes (HMW angiotensinogen) through association either with other angiotensinogen molecules or with some other protein(s) whose secretion by hepatocytes is stimulated by glucocorticoids and estrogens.
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PMID:Characterization of precursor and secreted forms of human angiotensinogen. 298 36

Specific binding sites for angiotensin II (Ang II) were identified in a human hepatoma cell line, HepG2. Binding of [125I]-Sar1 Ang II to these cells showed a high-affinity site with a Kd of 2.4 +/- 0.2 nmol/l. This specific binding was not changed during the cell cycle and showed no alteration after 24 h of treatment with Sar1-Ang II (10(-8) mol/l). Exposure of HepG2 cells to the Ang II agonist Sar1-Ang II caused a dose-dependent decrease in angiotensinogen production. The maximal inhibitory effect was at a dose of 10(-6) mol/l Sar1-Ang II which elicited 67% inhibition of angiotensinogen production after 24 h (control: 2.015 +/- 0.5 micrograms angiotensinogen/mg DNA; Sar1-Ang II 10(-6) mol/l: 0.68 +/- 0.03 micrograms angiotensinogen/mg DNA). Fifty per cent inhibition was obtained at a dose of 10(-9) mol/l Sar1-Ang II. Angiotensin II had a less marked effect, showing maximal inhibition of 40%. This study shows that the HepG2 cells possess specific Ang II binding sites and that Ang II analogues induce a dose-dependent inhibition of angiotensinogen production in cell culture.
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PMID:Regulation of angiotensinogen production by angiotensin II analogues. 324 Dec 35


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