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)

We have found that butyrate selectively inhibits hormonal induction of a few specific proteins and messenger RNAs in hepatoma cells. The fatty acid salt reversibly abolishes induction of tyrosine aminotransferase by dexamethasone and dibutyryl cyclic AMP in HTC cells by inhibiting the production of tyrosine aminotransferase messenger RNA. Half-maximal inhibition of enzyme induction occurred in 0.9 mM butyrate. This effect is highly specific, since 4 h after the addition of butyrate to induced HTC cells, the relative abundance of only five messenger RNA species out of several hundred observable on two-dimensional gels of translational products is changed. Upon removal of the butyrate from cell cultures pretreated with dexamethasone, tyrosine aminotransferase activity begins to increase more rapidly than if dexamethasone is added to control cultures, indicating that part of the induction process occurs in the presence of butyrate. A dose-dependent reduction of fast histone acetylation by butyrate was demonstrated by treating cells with butyrate followed by a short pulse with [3H]acetate and chase in a high concentration of butyrate. The butyrate concentration test range over which rapid histone acetylation is inhibited is similar to that which inhibits enzyme induction to the same extent. In contrast, the slow form of histone acetylation is unaffected in the concentration range examined. The induction of tyrosine aminotransferase by dexamethasone is delayed in hypoacetylated cells. This lag is consistent with the time required to initiate the recovery of the fast form of histone acetylation after its transient disappearance (Covault, J., Perry, M., and Chalkley, R. (1982) J. Biol. Chem. 257, 13433-13440). We conclude that sodium butyrate interferes with the ability of dexamethasone and dibutyryl cyclic AMP to increase production of several specific species of messenger RNA in hepatoma cells. This effect correlates well with its ability to reduce rapid acetylation of histones in HTC cells; we discuss potential roles of rapid histone acetylation in modulating hormonal stimulation of transcription.
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PMID:Inhibition by sodium butyrate of enzyme induction by glucocorticoids and dibutyryl cyclic AMP. A role for the rapid form of histone acetylation. 619 55

Cytoskeletal residues obtained after extraction of rat liver and cultured rat hepatoma cells (line MH1C1) were used to isolate cytokeratin subunit complexes by solubilization in low salt buffer containing 4 M-urea. Alternatively, the complexes were prepared by solubilization of total cytoskeletal proteins in 9.5 M-urea or 6 M-guanidinium hydrochloride (Gu . HCl), followed by separation using reversed phase high pressure liquid chromatography and dialysis first against either 9.5 M-urea or 6 M-Gu . HCl and then against buffers containing either 4 M-urea or 2 M-Gu . HCl, respectively. The complexes contained only two cytokeratin polypeptides in a 1 : 1 ratio as demonstrated by electrophoresis and isoelectric focusing, i.e. components A (Mr 55,000; isoelectric point in 9.5 M-urea, pH 6.4) and D (Mr 49,000; isoelectric point, pH 5.38) which were separated from each other at urea concentrations higher than 7 M. The complex had a sedimentation coefficient S25,w of 4.96 S in 2 M-Gu . HCl. Sedimentation equilibrium analysis gave an average Mr value of 207,000 which was interpreted as a tetramer containing two chains each of A and D. This complex was also directly demonstrated by gel electrophoresis under non-dissociating conditions. Using dimethyl suberimidate to cross-link the complex in solution of 4 M-urea or 2 M-Gu . HCl, we identified covalently linked heterodimers of A and D, and a tetrameric unit containing equal amounts of A and D which was the largest cross-link product obtained. This complex was similar to the tetrameric complex of rat and human vimentin formed under the same conditions. The constituents of the cross-linked products were identified by two-dimensional ("diagonal") gel electrophoresis, involving the cleavage of the bis(amidine) cross-links after the initial separation in the first dimension. Identical cross-link products were recognized when cytokeratin filaments were used. By electron microscopy the complexes appeared as threads of 2 to 3 nm diameter with a mean length of approximately 48 nm. On dialysis to low salt buffer, the complexes formed 2 to 3 nm protofilaments, intertwisted 3 to 4 nm protofilaments and typical 7 to 11 nm intermediate-sized filaments. Complexes formed from equivalent cytokeratins of other species such as man and cow, as well as heterologous recombinations such as human component A mixed with bovine component D and vice versa, showed the same characteristics.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Heterotypic tetramer (A2D2) complexes of non-epidermal keratins isolated from cytoskeletons of rat hepatocytes and hepatoma cells. 620 69

Cultured rat hepatoma cells (HTC-cells) were used to study the transfer of copper from a well-defined medium to and across the cell membrane and particularly the role of albumin in this process. HTC-cells, maintained in a minimal salt-glucose medium, accumulated far more copper than when maintained in the same medium, but supplemented with albumin. In the latter case, the Cu uptake strongly depended on the molar Cu/albumin ratio. The results suggest a role of albumin in the uptake of trace metals. The results indicate the presence of two types of binding sites for copper on the cell membrane. The sites of the first type bind copper very strongly and are probably responsible for the uptake of copper under physiological conditions. Their number was estimated to be about 10(6) per cell. Those of the second type only bind copper when the molar Cu/albumin ratio exceeds a value of about 1, i.e., under extreme, unphysiological conditions. Furthermore, the results suggest a direct interaction of the Cu-albumin complex with these strong binding sites as a first step in Cu uptake processes.
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PMID:Trace metal uptake in liver cells. 1. Influence of albumin in the medium on the uptake of copper by hepatoma cells. 650 60

To investigate the efficacy of long term administration of salt-poor albumin in the prognosis of cirrhotic patients with ascites, we administered albumin for more than six months at regular intervals to nine cirrhotic patients who had been confirmed to have ascites for the first time, and maintained their serum albumin levels above 3.0 g/dl. The other 11 cirrhotic patients who had also developed ascites for the first time were treated with diuretics only, as a control group. In the albumin treated group, one patient developed a hepatoma, and another had acute viral hepatitis after transfusion during splenectomy, and they were excluded. In the control group, one developed chronic liver failure after an operation for choledocholithiasis, and she was excluded from the study. All seven patients who had been administered albumin survived for more than two years, whereas three out of 10 in the control group died of chronic liver failure within two years. In the patients who showed a B.S.P. retention rate of more than 35% at the beginning of the study, all five treated with albumin survived for more than two years, whereas three out of four in the control group died within two years (P less than 0.025). In the albumin treated patients, the increase in serum albumin level was generally accompanied by an increase in the choline-esterase level. Long term administration of serum albumin to cirrhotic patients with ascites appears to lead to a better prognosis.
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PMID:Influence of long-term administration of serum albumin on the prognosis of liver cirrhosis in man. 661 54

Eukaryotic initiation factor 2 (eIF-2) preparations from mid-log and plateau-phase Yoshida ascites hepatoma AH 130 cells, from the liver of Yoshida ascites tumor-bearing rats and from 4-dimethylaminoazobenzene (DAB)-induced liver tumor tissue were assayed for ternary complex formation with 3H-met-tRNAf and GTP on nitrocellulose filters. The eIF-2 factor was extracted from postnuclear homogenate supernatants by high-salt wash and purified by ion exchange chromatography on DEAE-cellulose and phosphocellulose. The results here reported demonstrate changes of 3H-met-tRNAf X eIF-2 X GTP ternary complex formation under the conditions studied. Higher rates of ternary complex formation are present in control rat liver and in DAB-induced liver tumor tissue. The liver of Yoshida ascites tumor-bearing rats and the Yoshida ascites hepatoma cells show reduced rates of ternary complex formation, that are mostly evident at the plateau-phase of the intraperitoneal ascites cell growth. The present observations may be attributable to changes in the growing conditions of plateau-phase ascites cells, with accumulation in Gl phase, affecting the ability of eIF-2 to enter in the sequential assembly of the eukaryotic protein synthesis initiation complex.
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PMID:eIF-2 initiation factor activity in Yoshida ascites hepatoma AH 130 cells and in 4-dimethylaminoazobenzene-induced liver tumor tissue during growth. 681 8

The antigenicity and composition of chromatins differ markedly in chromatin preparations obtained by different procedures. Rat Novikoff hepatoma chromatin (NC) obtained by the "salt precipitation" and the micrococcal nuclease digestion procedures using significant levels of EDTA and NaCl each shows a common complement fixation (CF) capacity, exceeding chromatin preparations obtained from normal rat liver when tested with rabbit antisera raised to dehistonized NC. In contrast, "structured" NC preparations, which have been postulated to retain a native physical conformation, show minimal CF capacity when tested with the same antiserum but show high CF following elution of histones. While further progressive elution of non-histone proteins (NHPs) did not alter the CF capacity per unit DNA, the completely separated DNA and NHP fractions each showed minimal CF. The data suggest that the antigens detected in the CF assay predominantly represent an artifactual but specific complex of DNA and NHP arising from a denaturation of the native chromatin following elution of metal ions or histones. A qualitatively similar profile of NHPs in salt-precipitated NCs shows a range of total protein/DNA ratios, suggesting that the NHPs found in chromatin preparations may not be intrinsic to the native chromatin structure.
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PMID:Effects of divalent metal cations on composition and neoplasia-specific antigenicity of chromatins. 688 42

A major cell surface sialoglycoprotein with Concanavalin A receptor activity has been isolated from rat Zajdela ascites hepatoma cells. The sialic acid residues of the plasma membrane glycoproteins were specifically labeled by oxidation and NaIO4 followed by reduction with NaB3H4. Surface-labeled glycoproteins were released by short incubations with TPCK-trypsin at 37 degrees C and then separated by gel filtration on Sepharose 6B column. The predominantly labeled fraction, GP II2, was then purified by chromatography on DEAE-cellulose equilibrated with 0.05 M phosphate buffer, pH 7.5, and eluted with increasing molarities of NaCl. It was shown to be homogeneous by protein and carbohydrate staining on SDS-polyacrylamide gels, isoelectric focusing, rechromatography on DEAE-cellulose and immunoelectrophoresis. It has an apparent molecular weight of 110,000 daltons. The location of GP II2 on the cell surface was confirmed by the fact that it could be labeled metabolically with D-(3H) glucosamine and externally through the nonpenetrating periodate-NaB3H4 system. GP II2 could not be removed from the cell surface by high salt concentrations, chelator, or chaotropic agents but was released from the membrane by detergents. This suggests that GP II2 could be an integral protein. Analysis of the carbohydrate composition of GP II2 revealed galactose, N-acetylglucosamine, N-acetylgalactosamine, and sialic acid as major constituents and mannose as a minor one. This suggests that it contains carbohydrate chains both O- and N-linked to the polypeptide chain, most of them being O-linked. Finally, GP II2 has a potent Concanavalin A receptor activity. It inhibits the interaction between Concanavalin A and hepatoma cells and suppresses its effects on hepatoma cell proliferation.
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PMID:Purification and characterization of a major cell surface glycoprotein in Zajdela ascites hepatoma cells which displays a potent concanavalin A receptor activity. 706 81

Chromatin fragments generated in normal liver and solid hepatoma nuclei due to the action of endogenous nucleases and in ascites hepatomas nuclei treated with micrococcal nuclease differ in the ability to be released from the nuclei into a medium of low ionic strength. It is suggested that such a fractionation is based on different solubility of DNP fragments attached to the nuclear skeleton and of those that are not bound with it. DNP fragments extracted in a low-salt buffer contain all five histones with a negligible admixture of nonhistone proteins having the protein/DNA ratio about 1.1. No endogenous RNA-polymerase activity could be detected in these DNP fragments. The bulk of the RNA-polymerase activity is found in the matrix-associated DNP fragments that appear to be enriched in nonhistone proteins (their protein/DNA ratio amounted to 2.5). The possibility that transcribable DNP fragments are associated with the matrix through low-salt-stable linkages like those in the DNA-(RNA-polymerase-RNA or RNP)-matrix seems to be confirmed by the data obtained.
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PMID:[Proteins and the functional properties of the chromatin fractions from the nuclei of the normal liver and of experimental hepatomas]. 709 11

The activity on ribosome monomers of dissociation factor preparations obtained by high salt wash from ribosomes and from the post-ribosomal supernatant (cytosol) of Yoshida rat ascites hepatoma and Ehrlich mouse ascites carcinoma cells and from the liver of control and tumor-bearing animals has been determined at different periods of intraperitoneal tumor growth. The concentration of the polyamines spermine, spermidine and putrescine has also been measured under the same conditions. Results here reported show the presence of an association factor activity on subunit ribosomes at low Mg2+ concentrations in the post-ribosomal supernatant fractions of Yoshida ascites hepatoma and Ehrlich ascites carcinoma cells during tumor growth. An association factor activity also takes place in the ribosomal high salt wash extracts of Yoshida ascites cells at the terminal stages of tumor growth. Since an increase of spermidine to putrescine ratios occurs during tumor growth the changes in the rate of ribosome monomer dissociation into units here observed might be attributable, at least in part, to changes in polyamine concentrations under the conditions studied.
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PMID:Reassociation of eukaryotic ribosomal subunits and polyamine concentration in Yoshida ascites hepatoma and Ehrlich ascites carcinoma cells during growth. 721 13

We have studied the pattern of histone acetylation in intact rat hepatoma tissue culture (HTC) cells, in isolated HTC nuclei, and in chromatin prepared from these cells. The results have been compared with the histone acetylation observed in a reconstituted in vitro system consisting of a variety of purified soluble nucleosomal substrates, [3H]acetyl-CoA, and one of two different purified histone N-acetyltransferases. Acetylase A, a highly purified nuclear enzyme, catalyzed the acetylation of 1) nucleosomally bound histones in the order H4 > H2a = H2b > H3, and 2) free histones in the order H4 > H3 > H2b > H2a. Acetylase B, a cytoplasmic enzyme, modified only free histone H4, and it failed to acetylate histones in nucleosomes. The pattern of histone acetylation obtained by in vitro reaction of purified nucleosomes with the purified nuclear acetylase A differed considerably from the corresponding patterns obtained either by acetate labeling of intact cells, or by the acetyl-CoA labeling of nuclei and crude preparations of nucleosomes, as catalyzed by endogenous chromatin-bound acetylase(s). The most striking difference was in the relative preference for acetylation of histone H4 versus acetylation of histone H3: with the purified acetylase, histone H4 in nucleosomes was acetylated to a much greater extent than was histone H3, whereas the reverse preference was found with the endogenous acetylase(s). This result suggests that either a second nuclear acetylase enzyme, or a separate cofactor for acetylase A, is required for histone H3 acetylation in vivo. In support of this view, we find that the acetylation of histones H4, H2a, and H2b in nuclei is inhibited by urea, salt, or N-ethylmaleimide treatments to a very different extent than is the acetylation of histone H3. By comparing n-butyrate-treated HTC cells with untreated cells, classes of nucleosomes specially accessible and inaccessible to acetylation can be distinguished (Cousens, L. S., Gallwitz, D., and Alberts, B. M. (1979) J. Biol. Chem. 254, 1716-1723). Both types of special nucleosomal reactivities were present in isolated nuclei, but were lost as nucleosomes were purified from these cells. OUr data thus suggest the existence of labile specificity factors or structures, which guide the acetylase(s) to restricted groups of otherwise similar nucleosomes in vivo.
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PMID:Comparative studies of histone acetylation in nucleosomes, nuclei, and intact cells. Evidence for special factors which modify acetylase action. 744 May 48


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