Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The two human hepatoma cell lines, HepG2 and Hep3B, have been demonstrated to metabolize ethanol efficiently even in the absence of alcohol dehydrogenase. By using specific metabolic inhibitors, it was found that the microsomal ethanol-oxidizing system (MEOS) plays a significant role in ethanol metabolism in these two cell lines. There is a strong positive correlation between the rates of ethanol metabolism and the total cytochrome P-450 levels in the hepatoma cells. The involvement of the cytochrome P-450 system was further supported by the induction of aniline p-hydroxylase activity after ethanol treatment. However, the 3- to 4-fold elevation in aniline p-hydroxylase activity was not accompanied by an increase in cytochrome P450IIE1 mRNA level. Exposure of HepG2 and Hep3B cells to ethanol resulted in an increase of accumulation of apoA-I (15%-45% over control) in a dose-dependent manner (from 5 to 50 mM) of ethanol over a 24-hr period. All other major apolipoproteins which included apo CII, apo CIII and apoE, with the exception of apoB, were not affected by these treatments. At a concentration of ethanol of 25 mM or greater, accumulation of apoB, VLDL and LDL triglyceride were increased by 20% to 25% over the control level. Elevation of HDL cholesterol (40%-70% over control) was observed when the cells were exposed to an ethanol concentration of > or = 10 mM. Metyrapone, which inhibited the MEOS, was capable of blocking the induction of apoAI caused by ethanol treatment.
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PMID:Effect of ethanol on lipoprotein secretion in two human hepatoma cell lines, HepG2 and Hep3B. 133 18

C1027, a new macromolecular peptide antitumor antibiotic produced by Streptomyces globisporus C1027, shows extremely potent cytotoxicity to cultured cancer cells. The antibiotic is composed of an apoprotein and a chromophore and the latter serves as the active part of the compound. C1027 was separated into apoprotein and chromophore by methanol extraction and the separated parts can be reconstituted to form the active C1027 molecule in phosphate buffer. For determination of the specificity of C1027 reconstitution, the apoprotein was incubated with epirubicin and the chromophore was incubated with H16, a McAb directed against hepatoma cells. Notably, the reconstitution of C1027 occurred neither between apoprotein and epirubicin nor between chromophore and IgG molecule. In addition, bovine serum albumin showed no competition with C1027 apoprotein in binding to the chromophore. Various methods for linking C1027 to McAb were studied and two kinds of immunoconjugates have been prepared: (1) direct conjugate was made by linking C1027 to McAb, using SPDP as a linker agent, (2) assembled conjugate was made by linking and reconstitution, including 3 steps. Firstly, the chromophore was extracted with methanol and stored at -70 degrees C in drak. Secondly, the apoprotein was conjugated to McAb by SPDP and finally the extracted chromophore was added to the McAb-apoprotein conjugate. Determined by clonogenic assay, the IC50 values for hepatoma cells were 42 pmol/L, and 5.5 pmol/L, respectively, for direct conjugate and assembled conjugate. The IC50 value of M3-C1027 assembled conjugate prepared by linking the irrelevant McAb M3 to C1027 was 1,400 pmol/L.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Antitumor activity of new antitumor antibiotic C1027 and its monoclonal antibody assembled conjugate]. 144 79

The synthesis and secretion of apolipoprotein (apo) E, a major protein component of very low density lipoproteins, were examined in the human hepatoma cell line HepG2 under metabolic conditions known to stimulate lipogenesis and the production of apoB-containing lipoproteins. When HepG2 cells were incubated in the presence of fetal bovine serum (5 or 10%) or canine chylomicron remnants (5 or 10 micrograms of protein), the secretion of triglycerides and cholesteryl esters of lipoproteins of d less than 1.063 g/ml increased, as determined by the incorporation of [14C]acetate. Determination of the distribution of apoE among media lipoproteins by agarose column chromatography showed that the majority of secreted apoE was associated with large lipoproteins when cells were incubated with fetal bovine serum. However, immunoblot analysis of total media apoE revealed that incubating cells with or without the lipogenic factors had no effect on the amount of apoE secreted. Pulse-chase and continuous labeling experiments demonstrated that the synthesis and secretion of apoE did not vary under the different metabolic conditions, even though there was a 5-fold increase in apoB secretion in response to increased lipogenesis. Neither apoE nor apoB mRNA levels responded to the lipogenic stimuli. We conclude that the synthesis and secretion of apoE are independent of the production of apoB-containing lipoproteins in HepG2 cells.
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PMID:Synthesis and secretion of apolipoprotein E occur independently of synthesis and secretion of apolipoprotein B-containing lipoproteins in HepG2 cells. 155 3

The regulation of low-density lipoprotein (LDL) receptor activity, protein synthesis, and cellular mRNA content was evaluated in the human hepatoma cell line Hep G2. Incubation of the cells with LDL led to a complete downregulation of LDL receptor mRNA and LDL receptor protein synthesis. This LDL regulation of the LDL receptor and its mRNA was both time- and concentration-dependent. In contrast to protein synthesis and cellular mRNA concentrations of the LDL receptor, which were reduced to undetectable levels by prolonged incubation in the presence of LDL, LDL receptor activity was reduced to only 44% of preincubation levels. These findings support the presence of a second metabolic pathway for LDL uptake in human hepatocytic cells. The effect of LDL on cellular LDL receptor expression was specific for LDL because incubation in the presence of HDL did not affect any of these study end points. The potential coordinate regulation of the expression of the LDL receptor with its principal ligands, apolipoproteins (apo) B and E, was also investigated. In contrast to the LDL receptor mRNA downregulation with LDL incubation, cellular apoB and apoE mRNA concentrations were not affected by either LDL or HDL. Secretion of apoB, however, was significantly increased by incubating Hep G2 cells with LDL. These findings indicate that, in contrast to LDL receptor which is regulated at the mRNA level, the ligands for the LDL receptor are regulated either co- or post-translationally.
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PMID:Regulation of LDL receptor, apoB, and apoE protein and mRNA in Hep G2 cells. 160 52

Interactions of lipoproteins containing apolipoprotein (apo) A-I with or without apoA-II with human hepatoma cell line HepG2 were studied to investigate the ligand specificity for high density lipoprotein receptor on human hepatic cells and their metabolism. The two types of lipoproteins were isolated by immunoaffinity chromatography, in which apoE-containing lipoproteins were removed. Specific binding kinetics at 0 degrees C were observed for the apoA-I-containing lipoproteins with or without apoA-II (Kd = 18 or 20 micrograms protein/ml, Bmax = 110 or 120 ng/mg cell protein, respectively). The binding of these lipoproteins to HepG2 cells was competitively inhibited by excess unlabeled apoA-I-containing lipoproteins or apoA-I-phospholipid complexes, but not by apoA-II.phospholipid complexes. Interactions of these lipoproteins with HepG2 cells at 37 degrees C were further examined. These results suggested that HepG2 cells have a specific binding site for apoA-I-containing lipoproteins, and that apoA-I might be a crucial component in the binding of these lipoproteins to human hepatic cells.
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PMID:A specific binding site for lipoproteins containing apolipoprotein A-I on human hepatoma cell line HepG2. 166 78

Conditioned medium from human monocyte-macrophages incubated under various conditions was tested for its ability to stimulate fibrinogen mRNA levels in the hepatoma cell line HepG2. Recombinant human interleukin-6 (IL-6) stimulated fibrinogen mRNA levels 4.4-fold over control levels; this response was blocked by an anti-IL-6 antibody. Conditioned medium from 3-day-cultured monocyte-macrophages produced a slight stimulation of fibrinogen synthesis in HepG2 cells which was enhanced when the monocyte-macrophages had been treated with lipopolysaccharide (LPS). This stimulation was blocked by the anti IL-6 antibody. The cytokines, interleukin-1 (IL-1) and tumour necrosis factor (TNF) were also detected in the conditioned medium from the 3-day-cultured monocyte-macrophages. Monocyte-macrophages were cultured for 17 days and then incubated with acetylated low density lipoprotein (AcLDL) for 48 h. Such cells were 'foamy' in appearance and showed a 4-fold increase in apoE mRNA and a 10 to 50-fold increase in apoE secretion. This increase in apoE production was suppressed by almost a third when cells were coincubated with AcLDL and LPS. Conditioned medium from these 17-day-cultured AcLDL-treated human monocyte-macrophages did not stimulate fibrinogen mRNA synthesis in HepG2 cells, nor did the conditioned medium contain detectable levels of cytokines. These results suggest that cytokine production from foam cells in the atherosclerotic lesion is unlikely to be a major contributing factor in determining the elevated fibrinogen levels seen in the plasma of patients with IHD.
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PMID:Cytokine production by cholesterol-loaded human peripheral monocyte-macrophages: the effect on fibrinogen mRNA levels in a hepatoma cell-line (HepG2). 193 38

Rat hepatoma cells (Fu5AH) were studied as a model for the net delivery of apoE-free high-density lipoprotein (HDL) cholesterol to a cell. Incubating cells with HDL results in 1) a decrease in both media-free cholesterol and cholesteryl ester concentration; 2) decreased cell sterol synthesis; and 3) increased cell cholesteryl ester synthesis. HDL cholesteryl ester uptake is increased when cells are incubated for 18 hr in cholesterol poor media. Coincubation of 3H-cholesteryl ester-labeled low-density lipoprotein (LDL) with 50 microM chloroquine or 25 microM monensin results in a decrease in the cellular free cholesterol/cholesteryl ester (FC/CE) isotope ratio, indicating an inhibition in the conversion of cholesteryl ester to free cholesterol. In contrast, chloroquine and monensin do not alter the cellular FC/CE isotope ratio for 3H-CE HDL. This evidence indicates that acidic lysosomal cholesteryl ester hydrolase does not account for the hydrolysis of HDL-CE. Free cholesterol generated from 3H-cholesteryl ester of both LDL and HDL is reesterified intracellularly. At higher HDL concentrations (above 50 micrograms/ml) HDL cholesteryl ester hydrolysis is sensitive to chloroquine. We propose that an extralysosomal pathway is operating in the metabolism of HDL cholesterol and that at higher HDL concentrations a lysosomal pathway may be functioning in addition to an extralysosomal pathway.
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PMID:Evidence for extralysosomal hydrolysis of high-density lipoprotein cholesteryl esters in rat hepatoma cells (Fu5AH): a model for delivery of high-density lipoprotein cholesterol. 199 16

The apoprotein A-I (apo A-I)-containing lipoprotein (LPHuH-7apoA-I) was isolated from the concentrated conditioned medium of human hepatoma-derived cell line HuH-7 by immunoaffinity chromatography. LpHuH-7apoA-I consists of two kinds of lipoproteins. One is a lipoprotein of large particle size (LpL) with broad electrophoretic mobility on agarose gel ranging from the origin to the position of prebeta-lipoprotein. LpL is protein-rich in composition (protein, 75.4% by weight) and is heterogeneous in size (34-17 nm in diameter) electron microscopically. However, the most intriguing properties of LpL are its partial electrophoretic mobility towards the cathode on agar gel. The other lipoprotein is of small particle size (LpS). It demonstrates prebeta-electrophoretic mobility on agarose gel. LpS is also protein-rich in composition (protein, 95.4% by weight) and is heterogeneous in size (16.5-8.4 nm in diameter) electron microscopically. LpL is obviously different from LP-X and LP-Y in property, although LP-X, LP-Y and a part of LpL migrate towards the cathode on agar gel electrophoresis. LpS is also different from human apo A-I-containing lipoprotein without apo A-II in property, although these two lipoproteins possess the same mobility on agarose gel electrophoresis. These results indicate that both LpL and LpS are novel lipoproteins which have not yet been reported. The major isoproteins of the apo A-I of LpHuH-7apoA-I are apo A-I isoprotein 2 (apo A-I2), apo A-I isoprotein 4 (apo A-I4) and apo A-I isoprotein 5 (apo A-I5), and are different from those of apo A-I in human plasma and in the conditioned medium of hepatoma-derived cell line HepG2. This result suggests the presence of a proteinase which converts proapoprotein A-I (apo A-I2) to apoprotein A-I (apo A-I4) in the conditioned medium of HuH-7.
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PMID:Novel apoprotein A-I-containing lipoprotein produced by a human hepatoma-derived cell line HuH-7. 217 65

The cellular metabolism of apoE-free HDL (HDL) was studied in rat hepatoma cells (FU5AH). Cells incubated with HDL showed a dose-dependent decreased incorporation of [14C]acetate into cell sterol, indicating a net cholesterol delivery to the cells. HDL was localized both at the cell surface and inside the cell. This conclusion was drawn from both the association of 125I-labeled HDL with the cells under different experimental conditions and morphological evidence based on the association of colloidal gold-labeled HDL with the cells. Up to 63% of the 125I-labeled HDL protein initially inside the cell was subsequently recovered in the media as trichloroacetic acid precipitable (TCA-ppt) protein after a 30-min, 37 degrees C chase with a 100-fold concentration of unlabeled HDL. About 27% of the TCA-ppt apoprotein originally inside the cell was recovered as TCA-soluble material. Thus, we conclude that of the HDL apoprotein taken up by the cells, the majority is resecreted by a retroendocytosis pathway. The quantity of HDL apoprotein reappearing in the media was stimulated by the presence of unlabeled HDL in the media, while the amount of TCA-soluble material produced was not. Retroendocytosis of HDL was inhibited at 0 degree C and by the presence of 10 mM NaCN, 20 mM 2-deoxy-D-glucose in the media. Thus, the pathway appears to be both temperature- and energy-sensitive. HDL resecreted by the cell were depleted of cholesteryl ester and showed an altered size distribution, indicative of lipoprotein catabolism and remodeling. This study provides evidence for the existence of an endocytosis-retroendocytosis pathway for HDL apoproteins in a rat hepatoma cell and for the possibility that the endocytosis-retroendocytosis pathway may be involved in lipid delivery to the cell.
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PMID:Metabolism of apoE-free high density lipoproteins in rat hepatoma cells: evidence for a retroendocytic pathway. 232 43

Experiments were performed to evaluate the utility of a perfluorochemical emulsion as an artificial blood substitute for studies of lipoprotein metabolism in rats. Perfusing the liver of fed rats with perfluorochemical emulsion FC-34 at the same rate as a 20% red blood cell (RBC) perfusate, there was comparable oxygen uptake; however, there was a greater release of glucose and production of lactate than in RBC perfused livers. Under the stimulation of a low level of free fatty acid, there was less free fatty acid uptake and less triglyceride secretion in emulsion perfused livers. The lipoprotein secreted contained similar apoprotein, but there was a lower triglyceride to cholesterol ratio in the emulsion perfused liver. In addition to these moderate metabolic alterations, the uptake of radiolabeled chylomicron remnants by the perfused liver was almost completely suppressed when the perfluorochemical emulsion was used as an oxygen carrier. In vivo the presence of the perfluorochemical emulsion (5% of blood volume) decreased the rate of clearance of chylomicron remnants, beta-very-low-density lipoprotein (beta-VLDL) and cholesterol-rich high-density lipoprotein (HDLc), but not of low-density lipoprotein (LDL). In the presence of the emulsion, the degradation of 125I remnants, but not of [125I]LDL, by rat hepatoma cells was inhibited. The perfluorochemical emulsion did not inactivate lipoprotein lipase. The perfluorochemical emulsion did not change the triglyceride concentration or apoprotein composition of chylomicron remnants when they were incubated with the perfluorochemical emulsion at 37 degrees C for 1 hour and reisolated. The detergent used to solubilize the fluorocarbon FC-43, Pluronic F-68, did not affect the removal of chylomicron remnants in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of perfluorochemical artificial blood on lipoprotein metabolism in rats. 236 60


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