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)

Transglutaminase activity was reduced in malignant hepatoma, virus-transformed human and hamster cells, and chemically transformed mouse cells when compared to normal counterparts. The reduction in enzyme activity reflected the presence of fewer transglutaminase molecules in transformed cells. Greater amounts of the enzyme activity were particulate-associated in confluent and arrested normal human cells. Indirect immunofluorescence studies with antibody to cellular transglutaminase demonstrated the presence of transglutaminase in Triton X-100-insoluble material. A parallel between pericellular fibronectin and transglutaminase (TGase) was demonstrated. Normal human and mouse cells that elicited contact inhibition of growth and had the high TGase activity also had more epsilon-(gamma-glutamyl) lysine isopeptide bonds than transformed counterparts. Similarly nonproliferating human cells had higher transglutaminase activity and isopeptide levels than did proliferating populations. These results suggest that isopeptide bond formation stabilizes the cell membrane and contributes to a nonproliferating state. Inhibition of isopeptide formation should therefore lead to a mitogenic response. Preliminary results support such a relationship. A model depicting control of isopeptide formation at either enzyme or substrate level is presented.
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PMID:Transglutaminase and epsilon-(gamma-glutamyl) lysine isopeptide bonds in eukaryotic cells. 610 9

The native and one of the modified forms of tyrosine aminotransferase were purified from rat liver and characterized. Several hydrodynamic properties of the native enzyme are: Stokes radius, 46 A; subunit isoelectric point, 5.6; sedimentation coefficient, 5.6 S, frictional ratio, 1.44; diffusion coefficient, 4.65 X 10(-7) cm2 s-1; extinction coefficient of a 1% solution (w:v) at 280 nm, 10.5 cm-1. The molecular weight of the dimeric protein is 110,500 as calculated from the Stokes radius and sedimentation coefficient. The subunit of the modified form is of lower molecular weight than the subunit of the native enzyme and has a pI of about 5.9. During isoelectric focusing, both forms of the enzyme separate into two components. The more acidic component that is resolved from the native enzyme is phosphorylated, but the other component is not. The amino acid composition of native tyrosine aminotransferase differs from values reported for mixtures of the three forms of this enzyme. Neither the native nor the modified forms of the enzyme possess a free alpha-amino group as judged by dansylation, nor can they be digested with leucine aminopeptidase, implying that the NH2-terminus is blocked. The possibility that tyrosine aminotransferase is acetylated was examined by translating poly(A)+RNA from hepatoma cells in a cell-free translational system in the presence and absence of inhibitors of protein acetylation. [35S]Tyrosine aminotransferase synthesized in the presence of the inhibitors has a more basic isoelectric point than the native enzyme as determined by isoelectric focusing, suggesting that the enzyme is acetylated either at the NH2-terminal or the epsilon-amino group of an internal lysine. When digested by either of two lysosomal proteases, tyrosine aminotransferase is cleaved to a smaller size. These data show that tyrosine aminotransferase is susceptible to several post-translational modifications.
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PMID:Physical properties, limited proteolysis, and acetylation of tyrosine aminotransferase from rat liver. 611 52

Protamine sulfate reversibly inhibits serum-induced mitogenic stimulation of several nontransformed and neoplastic cell types in vitro. Fifty percent inhibition was induced by approximately 120-150 micrograms protamine sulfate/ml. Cells were affected directly, and inhibition depended on the duration of cell exposure. Heparin, chondroitin sulfate, heparan sulfate, and dextran sulfate neutralized protamine sulfate effects during the early stages of treatment. Nontransformed cells [bovine aortic endothelial cells, adult human gingival fibroblasts (strains 423 and 1101), fetal rat skin (strain 921-K) and muscle fibroblasts] required longer exposure to induce inhibition than did neoplastic cells [rat 3-methylcholanthrene-induced fibrosarcoma cell lines (MCA-6 and MCA-9), a macrophage-like cell line (NCTC-3749), Walker 256 rat carcinoma cells (ATCC-CCL-38), rat Morris hepatoma cells (ATCC-CCL-144), murine melanoma cells (B16), and rat bladder squamous cell carcinoma cells (804-G)]. Other polycationic compounds, including histone type VIII-S, poly-L-lysine, poly-L-arginine, and protamine (free base), were also effective inhibitors, whereas the basic proteins cytochrome c and lysozyme had no effect. Poly-L-histidine, poly-L-glutamic acid, poly-L-aspartic acid, and dextran blue also had no inhibitory effect.
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PMID:Protamine sulfate inhibition of serum-induced mitogenic responses: differential effects on normal and neoplastic cells. 621 Mar 90

The tripeptide H-Gly-His-Lys-OH (GHL) is a human plasma constituent which has been previously shown to modulate the growth and viability of a variety of cell types and organisms. Experimental observations presented herein indicate that GHL is complexed with the transition metal ions Cu++ and Fe++ in vivo and may exert its biological effects as a peptide-metal chelate. At physiological pH in vitro, GHL associates with ionic copper, cobalt, iron, molybdenum, manganese, nickel, and zinc, but has no affinity for calcium, manganese, potassium, and sodium. GHL acts synergistically with copper, iron, cobalt, and zinc to alter patterns of cell growth in monolayer cultures of a tumorigenic hepatoma cell line (HTC4). These transition metals induce cellular flattening and adhesion to support surfaces, and inhibit DNA synthesis and lactic acid production when growth is limited by reduction of serum concentrations in medium. These inhibitory effects are neutralized, and intercellular adhesion and growth are stimulated by GHL in medium at nanomolar concentrations. Cu and Fe are the most active metals when combined with GHL. The results suggest that the inability of HTC4 cultures to replicate without adequate concentrations of serum in medium may reflect deficiency of GHL and transition metals, which appear to form complexes prior to interaction with cells. Chelation of transition metals with GHL and, potentially, with other growth-modulating peptide factors in plasma or medium, may provide a mechanism for expression and regulation of biological activities influenced by transition metals and polypeptide growth factors. The observed effects of GHL-metal complexes, including stimulation of cellular adhesiveness to substratum (flattening) and intercellular attachment (monolayer formation), appear to satisfy requirements for growth of hepatoma cells in monolayer culture.
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PMID:Growth-modulating tripeptide (glycylhistidyllysine): association with copper and iron in plasma, and stimulation of adhesiveness and growth of hepatoma cells in culture by tripeptide-metal ion complexes. 624 26

In this study, we have density-labeled newly replicated DNA in hepatoma tissue culture cells and separated the newly replicated nucleoprotein from bulk material using density gradient centrifugation. These experiments indicate that only newly synthesized histones H3 and H4 deposit specifically on newly replicated DNA. Histones H2A and H2B show a partial preference and histone H1 shows no preference for deposition on new DNA. These experiments also indicate that for a whole cell cycle, the non-H1 histones remain associated with the same DNA upon which they were initially deposited. However, when that region is replicated during the next cell cycle, the histones distribute equally to both daughter strands. An increase or decrease in the level of histone modification (acetylation) induced by sodium butyrate treatment does not alter the in vivo stability of the histone-DNA interactions. Experiments which involved labeling SV40 minichromosomes with [3H]lysine confirm our observations that only newly synthesized histone H3 and H4 are selectively depend on replicated DNA.
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PMID:A reevaluation of new histone deposition on replicating chromatin. 626 16

Fixation by periodate/lysine/paraformaldehyde, a method purported to cross-link specifically plasma membrane glycoproteins, was evaluated using Novikoff rat ascites hepatocellular carcinoma cells. Cells were treated with periodate/lysine, periodate/glycine, and periodate/lysine/paraformaldehyde and subsequently reduced with NaB3H4. The glycoproteins labeled with 3H were resolved by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and visualized by fluorography. The effects of reactant concentrations on 3H-labeling of cellular components, cell viability, and cross-linkage of 3H-labeled proteins were examined. The effect of increasing the localized density of plasma membrane glycoproteins on the extent of cross-linkage by periodate and lysine was investigated using cells in which patching of the plasma membrane glycoproteins had been induced by ferritin-conjugated concanavalin A/rabbit antiferritin antiserum. Also investigated was the periodate-independent to mixtures of periodate and lysine or glycine. Results of these studies did not support a mechanism of cross-linking involving reaction between the free base lysin and aldehyde groups on periodate oxidized carbohydrate residues but suggested a complex interaction between periodate oxidized plasma membrane glycoproteins and polymeric complexes of lysine and formaldehyde.U
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PMID:Evaluation of periodate/lysine/paraformaldehyde fixation as a method for cross-linking plasma membrane glycoproteins. 626 47

The primary translation product of human apolipoprotein A-II was purified from wheat germ and ascites cell-free lysates programmed with RNA isolated from either a hepatocellular carcinoma cell line (HepG2) or intestinal epithelium. A-II mRNA represents 0.2% of the translatable RNA in these hepatocytes and in jejunal epithelium. Plasma high density lipoprotein-associated A-II is a 77-amino acid polypeptide. The primary translation product is 100 amino acids long and contains a 23-amino acid NH2-terminal extension. Cotranslational cleavage of the cell-free product indicated that this NH2-terminal sequence consists of an 18-amino acid long signal peptide, Met-Lys-Leu-Leu-Ala-Ala-X-Val-Leu-Leu-Leu-X-X-Cys-X-Leu-X-X-, and a 5-amino acid long propeptide, Ala-Leu-Val-Arg-Arg. This functional division was confirmed by sequencing the stable intracellular form of apolipoprotein A-II isolated from HepG2 cells. Approximately 45% of the proapo-A-II is cleaved to the mature form during export from HepG2 cells. The COOH-terminal dipeptide conforms to the rule that prosegments are cleaved after paired basic residues. We have previously shown (Gordon, J. I., Sims, H. F., Lentz, S. R., Edelstein, C., Scanu, A. M., and Strauss, A. W. (1983) J. Biol. Chem. 258, 4037-4044) that proapolipoprotein A-I is not cleaved during export from these cells and contains a prosegment with a COOH-terminal Gln-Gln dipeptide. Therefore, proteolytic processing of the two principal high density lipoprotein-associated apolipoproteins proceeds along different pathways.
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PMID:Biosynthesis of human preproapolipoprotein A-II. 631 18

Substrate-attached critical-point-dried cells cleave along the level of the substrate-adherent membrane if removed by means of adhesive tape. The remaining membrane fragments on grids can be visualized three-dimensionally by means of stereo transmission electron microscopy. Attachment of cells may be achieved by active spreading of the cell, or artificially by poly-L-lysine adherence of prefixed cells. In 11 different cell types a filamentous network appears to remain associated with the cytoplasmic face of the membrane. In one hepatoma cell type virtually no filamentous network could be detected. Two general network morphologies are described: the hepatocytic network and the lymphoid network. Since no correspondence could be found between cytoplasmic structure and the structure of the membrane-associated network, and since cells generally cleave along the level of this network, excluding cell organelles, we conclude that it comprises a distinct structural system, analogous to the membrane skeleton of the red cell membrane.
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PMID:Plasma membrane-associate filament systems in cultured cells visualized by dry-cleaving. 636 31

A single injection of dimethylnitrosamine (DMN) given to adult rats induces hepatocellular carcinoma if given during the period of restorative hyperplasia following partial hepatectomy. The effect of DMN on the sequence of biochemical events in regenerating liver is therefore of interest. As carcinogenesis is likely to involve a change in control of gene expression, and as evidence suggests that non-histone chromosomal proteins (NHP) are involved in gene control, the effect of DMN on synthesis of NHP in regenerating liver was studied. A well-defined group of NHP, the high mobility group (HMG), known to be specifically associated with DNA active in transcription, were investigated. Partial hepatectomy was found to cause a large increase in incorporation of [3H]lysine into HMG proteins; this did not occur immediately, but was apparent at the time of DNA synthesis and of mitosis. DMN did not alter the relative amounts of different HMG proteins in relation to histone H1, but the carcinogen caused a considerable reduction in incorporation of [3H]lysine. This decreased synthesis of the proteins which may function as gene derepressors may well be relevant in carcinogenesis.
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PMID:The effect of dimethylnitrosamine on the synthesis of high-mobility group non-histone proteins in regenerating rat liver. 645 84

When their membrane proteins were labeled with 125I by lactoperoxidase, dividing hepatoma cells lost radioactivity to the medium in a biphasic manner (T1/2 = 16-26 h, greater than 40 h). Lysosomotropic weak bases, chloroquine, and NH4Cl inhibited the rapid phase by 59%. More than 50% of the radioactivity which accumulates in the media from dividing cells during the first 4 h after labeling was trichloroacetic acid-soluble, and was identified as iodotyrosine. Iodotyrosine release from labeled membrane proteins was 60-71% inhibited by lysosomotropic agents chloroquine and NH4Cl as well as the sodium-proton ionophore, monensin. The inhibitory effect of NH4Cl and monensin was reversible. Inhibitors of microtubule and microfilament function and transglutamination had no effect on release of iodotyrosine to the medium, but trypsin-like protease inhibitors, p-aminobenzamidine, tosyl-L-lysine/chloromethylketone, and phenylmethylsulfonyl fluoride, as well as the cathepsin B inhibitor, leupeptin, inhibited by 21-24%. Iodotyrosine release showed a biphasic Arrhenius plot with an activation energy of 17 kcal/mol above but 27 kcal/mol below 20 degrees C. These results indicate that cell membrane polypeptides require a temperature-limiting event as well as passage through an ion-sensitive compartment prior to their complete degradation to constituent amino acids. In contrast to other lysosomal-mediated events, however, iodinated membrane proteins of dividing cells are degraded in a manner insensitive to agents which disrupt the cytoskeleton.
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PMID:Degradation of surface-labeled hepatoma membrane polypeptides: effect of inhibitors. 648 99


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