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

Transglutaminase (EC 2.3.2.13) activity in chemically induced rat hepatocellular carcinomas was reduced by some 65% when compared to normal rat livers. The majority of the remaining activity (approx. 85%) was found in the particulate fraction. The use of non-ionic detergent to extract the transglutaminase activity present in both normal and tumour tissue followed by its separation on a Mono-Q column revealed two distinct peaks of activity. These peaks of activity were equivalent to those previously identified as a membrane-bound transglutaminase and the more characteristic cytosolic or tissue transglutaminase. The ratio of the activity of the cytosolic enzyme to that of the membrane-bound enzyme in normal liver was calculated as 5:1. In hepatocellular carcinomas, this ratio was reduced to 0.4:1. No significant change in the activity of the membrane-bound enzyme was detectable in tumour tissue. Comparison of the cytosolic enzyme found in hepatocellular carcinomas with that found in normal liver indicated no change in its molecular weight, Km,app for putrescine incorporation into N,N'-dimethylcasein and sensitivity to activation by Ca2+. These observations suggest that the reduction in transglutaminase activity observed in the hepatocellular carcinoma is due to a selective reduction in the expression of the cytosolic transglutaminase.
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PMID:Expression of the cytosolic and particulate forms of transglutaminase during chemically induced rat liver carcinogenesis. 289 62

The synthesis and secretion of apolipoprotein B-100 (apoB-100) have been studied in a human hepatoma cell line, the Hep G2 cells. The time needed for the synthesis of apoB-100 was estimated to be 14 min, which corresponds to a translation rate of approximately 6 amino acids/s. ApoB-100 was compared with albumin and alpha 2-macroglobulin as to the distribution between the membrane and the luminal content in the endoplasmic reticulum (ER) and the Golgi apparatus. The results suggested that apoB-100 approximately followed the distribution of these secretory proteins in the Golgi, while the ratios between the percent membrane-bound apoB-100 and percent membrane-bound albumin or alpha 2-macroglobulin were 3-4:1 in the ER. This may suggest that apoB-100 occurs in a membrane-associated form in ER prior to the integration in the lipoproteins. Pulse-chase studies combined with subcellular fractionation was used to investigate the kinetics for the intracellular transfer of apoB-100. A 3-min pulse of [35S]methionine was followed by an increase in apoB-100 radioactivity in the ER during the first 10-15 min of chase. The following 10-15 min of chase were characterized by linear decrease in apoB-100 radioactivity with a decay rate of approximately 6%/min. The residence kinetics for apoB-100 in the ER differed from that of transferrin and probably also from that of albumin. By comparing the time for the pulse maximum in ER with that in the denser Golgi fractions the time needed for the transfer between ER and Golgi could be estimated to be 10 min. The time needed for the secretion of newly synthesized apoB-100 was estimated to be 30 min. This indicates that the transfer of the protein through the Golgi apparatus to the extracellular space requires 20 min.
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PMID:Pulse-chase studies of the synthesis and intracellular transport of apolipoprotein B-100 in Hep G2 cells. 302 51

It has been shown previously that the rat hepatoma no. 7288C grown in vivo or in vitro expresses fewer receptors which recognize chylomicron remnants than does normal rat liver, and it was suggested that this may contribute to the deletion of dietary cholesterol-induced regulation of cholesterol synthesis in hepatomas (Barnard, G., Erickson, S. and Cooper, A. (1984) J. Clin. Invest. 74, 173-184). To investigate this further, Buffalo rats bearing hepatomas (HTC no. 7288C) were made hypercholesterolemic by feeding an atherogenic diet and hypocholesterolemic by ethinyl estradiol injections. Under all circumstances, tumor membranes had fewer receptors than liver membranes as measured by specific binding of [125I]chylomicron remnants. Ethinyl estradiol treatment increased the number of lipoprotein receptors 1.7-fold in liver membranes and 1.2-1.6-fold in tumor membranes, but hypercholesterolemia did not produce any significant changes in remnant binding to either liver or hepatoma membranes. Feeding an atherogenic diet induced a 2.4-fold increase in total cholesterol content in the liver, primarily as cholesterol ester; however, there was no change in total, free or ester cholesterol in the hepatomas. Acyl coenzyme A:cholesterol acyltransferase activity was low in this hepatoma line and neither treatment significantly affected its activity. One explanation for the lack of effect of the atherogenic diet on hepatoma cholesterol metabolism in addition to the decreased number of lipoprotein receptors might be the failure of access of lipoproteins to the tumor cell. To assess this, radioiodinated apo E-rich lipoproteins of various sizes were injected intravenously into rats with hepatomas. Their disappearance from the circulation was followed, and the uptake of each lipoprotein into a variety of tissues was determined. Chylomicron remnants were the most avidly removed particles. VLDLH, IDLH and HDLC were removed more slowly and less completely. None of the lipoproteins accumulated substantially in the tumors suggesting a limited access to the hepatoma tissue. Thus, in addition to the observed reduction in lipoprotein receptor number, limited lipoprotein access to the hepatoma tissue may be a significant factor in contributing to the apparent lack of feedback regulation of cholesterol synthesis by hepatoma tissue in vivo.
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PMID:Regulation of lipoprotein receptors on rat hepatomas in vivo. 302 19

Plasma-membrane-bound kinases of AS-30D ascites from transplantable rat hepatocarcinoma were shown to extensively catalyze the phosphorylation of plasma membrane proteins and membrane lipids, using [gamma-32P]ATP or [gamma-32P]GTP as a phosphate donor. In contrast, plasma membranes from normal adult rat liver or fast-growing regenerating liver (24 h after partial hepatectomy) produce significantly less activity for protein phosphorylation and little phosphorylation of the lipids. However, neonatal (24 h old) rat liver plasma membrane preparations show levels of phosphorylation of proteins and lipids intermediate between those in the tumor cell line and normal adult plasma membrane preparations. Phosphatidic acid was identified as one of the 32P-labelled lipids in the tumor plasma membrane chloroform-methanol (2:1, v/v) extract. Phosphorylation of protein was not affected by cAMP or cGMP. However, calcium ion (in the presence or absence of calmodulin) significantly modifies the 32P labelling of a series of proteins in normal tissue but has little effect with the neoplastic preparations. Some plasma membrane proteins were capable of nucleotide binding, instead or in addition to being phosphorylated. Finally, the presence of membrane-bound phosphoprotein phosphatase(s) was also demonstrated in all the preparations examined by means of chase experiments with nonlabelled ATP or GTP, and (or) by the use of the phosphoprotein phosphatase inhibitor, orthovanadate.
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PMID:Endogenous hyperphosphorylation in plasma membrane from an ascites hepatocarcinoma cell line. 337 Jan 39

Biochemical and ultrastructural studies of insulin binding and cellular processing by cultured H4IIEC3 hepatoma cells were performed. Insulin binding and intracellular accumulation were rapid and after 30 min at 37 degrees C, 65% of the total cell-associated 125I-insulin was in an acid-stable compartment. Chloroquine had no significant effect on the amount of total cell-associated insulin or the percentage of insulin in the acid-stable compartment or cell-associated insulin degradation under those conditions, but after 60-min incubations, it slightly decreased the rate of dissociation of internalized hormone. Ultrastructural analysis revealed that monomeric ferritin-insulin (Fm-I) initially bound to single or paired receptors on microvilli. Within 5 min occupied insulin receptors microaggregated and migrated to the intervillous cell surface. During the next 5-10 min occupied receptors aggregated into large clusters on the plasma membrane. Large amounts of insulin were internalized by macropinocytosis and the majority of internalized Fm-I was found in phagosomes. Less than 10% of the membrane-bound insulin was associated with pinocytotic invaginations or coated pits and less than 5% of the total cell-associated insulin was found in lysosomes. Chloroquine had no detectable effect on the amount of Fm-I or its distribution among the intracellular organelles. These studies demonstrated that, compared to previous studies with rat adipocytes or 3T3-L1 adipocytes, insulin interalization and intracellular processing in this hepatoma cell were unique. These differences provide further evidence that insulin binding and processing may be controlled by cell-specific mechanisms and that substantial heterogeneity exists in pathways previously presumed to be similar for all cell types.
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PMID:Insulin binding and processing by H4IIEC3 hepatoma cells: ultrastructural and biochemical evidence for a unique route of internalization and processing. 354 44

We developed a method for selective preparation of two forms of alkaline phosphatase from rat tissues. The enzyme was extracted by n-butanol treatment at pH 5.5 and pH 8.5 as soluble and aggregated (membranous) forms, respectively. The soluble form prepared from liver was found to be identical with the serum enzyme. Complete solubilization of the membrane-bound enzyme without detergents had a great advantage in its purification. Rat hepatoma AH-130 cells enriched in alkaline phosphatase were first used for purification of the liver-type enzyme. The hepatoma enzyme, purified by chromatographies on concanavalin-A-Sepharose, Sephacryl S-300 and hydroxyapatite was used for production of antibodies specific for the liver-type isozyme. An immunoaffinity column, prepared with anti-(hepatoma-enzyme) IgG was utilized for the enzyme purification from other tissues including the membranous form. Analyses of amino acid composition of the purified enzymes revealed that all the liver-type enzymes from hepatoma, liver, kidney and serum had the same composition, whereas the intestinal type consisted of the composition distinctly different from that in the liver type. In addition, there was no significant difference in amino acid composition between the soluble and membranous forms, suggesting a possible involvement in the membranous form of a hydrophobic component other than its polypeptide domain. The present method for selective preparation of the soluble and membranous forms of alkaline phosphatase will be useful for a further investigation on the interaction of the enzyme with membranes.
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PMID:Selective preparation and characterization of membranous and soluble forms of alkaline phosphatase from rat tissues. A comparison with the serum enzyme. 376 22

1. The ribosomal components in the postmitochondrial supernatant of a rat hepatoma (hepatoma 7800) and the corresponding host liver were examined for diversity and functional competence. 2. The ;free' and ;membrane-bound' polyribosomes of both tissues were equally active in vivo and had equilibrated with newly synthesized ribosomes 4hr. after administration of [6-(14)C]orotic acid. 3. The inactive monomer-dimer pool in hepatoma 7800 was unattached to membranes and a larger fraction of the polyribosomes was free in hepatoma than in liver. 4. By using sensitivity to puromycin as a criterion, evidence was obtained that most of the polyribosomes in hepatoma 7800 were active in vivo. 5. Actinomycin, azaguanine and carbon tetrachloride caused marked conversion of polyribosomes into inactive monomers and dimers in the host liver and moderate conversion in the hepatoma. 6. Significant accumulation of ferritin and shifts in the mean polyribosome size to the lighter species occurred in the host liver of rats bearing large hepatomas.
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PMID:Diversity and nature of ribosomal pools in hepatoma 7800 and host liver. 430 Aug 30

Plasma membranes were isolated after binding liver and hepatoma cells to polylysine-coated polyacrylamide beads, and the effect of concanavalin A on the membrane-bound Mg2+ -ATPase and the Mg2+ -ATPase solubilized by octaethylene glycol monododecyl ether (C12E8) was studied. In the experiment of membrane-bound Mg2+ -ATPase, plasma membranes were pretreated with Concanavalin A and the activity was assayed. Concanavalin A stimulated the activity of both liver and hepatoma enzymes assayed above 20 degrees C. Concanavalin A abolished the negative temperature dependency characteristic of liver plasma membrane Mg2+ -ATPase. On the other hand, Concanavalin A prevented the rapid inactivation due to storage at -20 degrees C, which was characteristic of hepatoma plasma membrane Mg2+ -ATPase. With solubilized Mg2+ -ATPase from liver plasma membranes, the negative temperature dependency was not observed. Concanavalin A, which was added to the assay medium, stimulated the activity of the enzyme solubilized in C12E8 at a high ionic strength. However, Concanavalin A failed to show any effect on the enzyme solubilized in C12E8 at a low ionic strength. With solubilized Mg2+ -ATPase from hepatoma plasma membranes, Concanavalin A could not prevent the inactivation of the enzyme during incubation at -20 degrees C.
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PMID:Effect of concanavalin A on the activity of membrane-bound and detergent-solubilized Mg2+ -ATPase. 612 4

We isolated the soluble forms of gamma-glutamyltransferase (EC 2.3.2.2; gamma-GT) from adult and fetal human liver and primary hepatoma and compared their properties. The Km value for L-gamma-glutamyl-p-nitroanilide and glycylglycine, the Ki for anthglutin, and the pH optimum were identical for the enzyme from all three sources. Nor were significant differences observed among the three in their heat stability, inhibition by serine and borate, or ability to transfer the gamma-glutamyl moiety to various amino acids and dipeptides. Unlike membrane-bound gamma-GT, the soluble form from all three sources entered polyacrylamide gel and showed identical electrophoretic mobilities. Treatment with neuraminidase decreased the electrophoretic mobilities to a similar extent. The relative molecular mass of the enzyme from each of the three sources is about 84 000. Immunoinhibition and immunoprecipitation of gamma-GT from the three sources by antibody to fetal liver gamma-GT followed an identical pattern. Gamma-GT from fetal liver and hepatoma differed significantly from that of adult liver in affinity for wheat-germ agglutinin and Ricinus communis agglutinin (RCA-120). In many of the properties studied, soluble gamma-GT resembles the papain-digested form of membrane-bound gamma-GT.
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PMID:Soluble forms of gamma-glutamyltransferase in human adult liver, fetal liver, and primary hepatoma compared. 612 78

Gamma glutamyltransferase (GGT) is a membrane-bound enzyme that is involved in glutathione metabolism and aminoacids uptake. GGT activity is stimulated by a number of hormones and pharmacological agents in certain animal tissues. In rat liver, adrenalectomy causes a 2-fold decrease in GGT activity and hydrocortisone treatment of adrenalectomized animals specifically stimulates this enzyme activity. In a highly differentiated hepatoma cell line, Fao, GGT activity is similar to rat liver and is under glucocorticoids control. These hormones specifically stimulate GGT activity (2- to 3-fold). Translation and transcription inhibitors prevent the hormonal effect. The stimulation of GGT activity is therefore probably due to an increase in GGT mRNA synthesis. The results reported suggest that the Fao cell line is a very convenient system for the study of the molecular mechanisms of both the glucocorticoid effects on differentiated cells as well as the modulation of membrane-bound enzymes biosynthesis.
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PMID:The hormonal induction of gamma glutamyltransferase in rat liver and in a hepatoma cell line. 613 63


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