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 investigated the effect of camptothecin and adriamycin on [3H]TTP incorporation and bleomycin-stimulated [3H]TTP incorporation in host liver and hepatoma nuclei of rats. Camptothecin neither stimulated nor inhibited incorporation in the regular nuclear incorporating system. Bleomycin stimulated incorporation to a much greater extent in host liver nuclei and slow-growing hepatomas than it did in the fast-growing hepatoma 7777. Addition of camptothecin to bleomycin stimulated incorporation of [3H]TTP even further. This camptothecin stimulation was slightly greater in hepatoma nuclei than it was in host liver nuclei. Adriamycin inhibited [3H]TTP incorporation in the regular system as well as the bleomycin-induced incorporation. Hepatoma nuclei were more sensitive to this inhibition than were host liver nuclei. Sucrose density gradients indicated that camptothecin caused DNA strand scissions in addition to those produced by bleomycin. Camptothecin alone produced some single-strand but no double-strand scissions. The action of bleomycin was dependent on sulfhydryl-reducing agents. Camptothecin could partially substitute for this requirement. Adriamycin did not produce DNA breaks as determined by neutral or alkaline sucrose density gradients. Despite complete inhibition of bleomycin-induced [3H]TTP incorporation, adriamycin did not prevent bleomycin-induced DNA breaks. The inhibitory effect of adriamycin might have been on the repair system.
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PMID:Effect of camptothecin and adriamycin on bleomycin-induced tritiated thymidine triphosphate incorporation in a rat nuclear system. 6 12

Free polysomes were isolated from normal and regenerating rat liver and from Morris hepatomas 7777, 7800, 5123C and 9618A. Sucrose gradient analysis ruled out the possibility of any significant messenger RNA degradation in these polysome preparations. The ethylenediaminetetraacetate-disrupted polysomes were fractionated on oligodeoxythymidylic acid-cellulose columns. The column-bound polyriboadenylic acid-containing messenger ribonucleoprotein particles were eluted with a formamide buffer, precipitated with ethanol, and subjected to polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The messenger RNA-associated proteins from the different tissues were qualitatively similar, but two proteins with molecular weights of 66,000 and 109,000 found as minor proteins in normal liver appeared on gels as major protein bands when hepatoma messenger ribonucleoprotein particles were examined. The 66,000- and 109,000-molecular-weight proteins in these particles from regenerating liver appeared quantitatively similar to those isolated from normal liver.
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PMID:A comparison of polysomal messenger ribonucleoprotein particles from normal and neoplastic rat liver. 20 22

In the rat, expression of the CYP1A1 gene is closely associated with arylhydrocarbon hydroxylase (AHH) enzyme activity. AHH is an inducile enzyme activity known to play an important role in the bioactivation of polycyclic aromatic hydrocarbons (PAHs) to mutagenic and carcinogenic metabolites. PAH-induced expression of the CYP1A1 gene appears to be regulated by several trans-acting factors, including the Ah receptor and the 4S PAH-binding protein. In this study, we used the PAH isomers benzo[a]pyrene (BaP) and benzo[e]pyrene (BeP) to further evaluate the role of the 4S PAH-binding protein in induction of the CYP1A1 gene in H4-II-E rat hepatoma cells. Although BaP is believed to bind to both the Ah receptor and the 4S protein, BeP has been reported to bind exclusively to the 4S protein. The results of the study presented here indicate that BaP and BeP induce the expression of the CYP1A1 gene, as measured by ethoxyresorufin O-deethylase (EROD) activity, in a concentration-dependent manner. However, BaP is about 25 times as potent as BeP in inducing EROD activity in these cells. Slot-blot analysis of total RNA isolated from these cells indicated that BeP, BaP, and 3-methylcholanthrene increased the level of CYP1A1 mRNA expression. Sucrose-gradient analysis of BeP binding activity indicated that BeP bound with high affinity to the 4S PAH-binding protein, but not to the Ah receptor. These results suggest that the 4S protein may play a role in the PAH-induced expression of the CYP1A1 gene in rat H4-II-E cells.
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PMID:Induction of CYP1A1 gene expression in H4-II-E rat hepatoma cells by benzo[e]pyrene. 131 59

Insulin stimulates glucose transport in adipocytes via the rapid redistribution of the GLUT1 and GLUT4 glucose transporters from intracellular membrane compartments to the cell surface. Insulin sensitivity is dependent on the proper intracellular trafficking of the glucose transporters in the basal state. The bulk of insulin-sensitive transport in adipocytes appears to be due to the translocation of GLUT4, which is more efficiently sequestered inside the cell and is present in much greater abundance than GLUT1. The cell type and isoform specificity of GLUT4 intracellular targeting were investigated by examining the subcellular distribution of GLUT1 and GLUT4 in cell types that are refractory to the effect of insulin on glucose transport. Rat GLUT4 was expressed in 3T3-L1 fibroblasts and HepG2 hepatoma cells by DNA-mediated transfection. Transfected 3T3-L1 fibroblasts over-expressing human GLUT1 exhibited increased glucose transport, and laser confocal immunofluorescent imaging of GLUT1 in these cells indicated that the protein was concentrated in the plasma membrane. In contrast, 3T3-L1 fibroblasts expressing GLUT4 exhibited no increase in transport activity, and confocal imaging demonstrated that this protein was targeted almost exclusively to cytoplasmic compartments. 3T3-L1 fibroblasts expressing GLUT4 were unresponsive to insulin with respect to transport activity, and no change was observed in the subcellular distribution of the protein after insulin administration. Immunogold labeling of frozen ultrathin sections revealed that GLUT4 was concentrated in tubulo-vesicular elements of the trans-Golgi reticulum in these cells. Sucrose density gradient analysis of 3T3-L1 homogenates was consistent with the presence of GLUT1 and GLUT4 in discrete cytoplasmic compartments. Immunogold labeling of frozen thin sections of HepG2 cells indicated that endogenous GLUT1 was heavily concentrated in the plasma membrane. Sucrose density gradient analysis of homogenates of HepG2 cells expressing rat GLUT4 suggested that GLUT4 is targeted to an intracellular location in these cells. The density of the putative GLUT4-containing cytoplasmic membrane vesicles was very similar in HepG2 cells, 3T3-L1 fibroblasts, 3T3-L1 adipocytes, and rat adipocytes. These data indicate that the intracellular trafficking of GLUT4 is isoform specific. Additionally, these observations support the notion that GLUT4 is targeted to its proper intracellular locale even in cell types that do not exhibit insulin-responsive glucose transport, and suggest that the machinery that regulates the intracellular targeting of GLUT4 is distinct from the factors that regulate insulin-dependent recruitment to the cell surface.
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PMID:Intracellular targeting of the insulin-regulatable glucose transporter (GLUT4) is isoform specific and independent of cell type. 165 37

The 4 S polycyclic aromatic hydrocarbon (PAH)-binding protein had been implicated in regulating the expression of rat cytochrome P450IA1 which is most closely associated with aryl hydrocarbon hydroxylase (AHH). We have now investigated the presence of both the 4 S PAH-binding protein and the 8 S Ah receptor in rat hepatoma H4-II-E cells as well as the induction of P450IA1 upon their exposure to PAH's such as benzo[a]pyrene (BP) and 3-methylcholanthrene (3MC), and halogenated dioxins such as 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDBF). Sucrose density gradient analyses and hydroxylapatite assays indicate that, in addition to the 8 S protein, the 4 S PAH binding protein is present in these cells. This protein interacts in a saturable and high affinity manner with BP and 3MC, but not with TCDD or TCDBF. Using a P450IA1 probe, the induction of gene expression was observed by Northern blot analysis of total cellular RNA after exposure of the H4-II-E cells to BP, 3MC, or TCDBF. Since the 4 S protein was observed to interact only with BP and 3MC, these results suggest that this protein may also play a role in the PAH-induced expression of cytochrome P450IA1 gene expression in H4-II-E.
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PMID:Presence of the 4 S polycyclic hydrocarbon-binding protein in H4-II-E cells. 184 70

Exposure of Reuber hepatoma cells (RHC) to 30 and 300 fM human rIL-1 (hurIL-1) for 4 h significantly decreased cytosolic glucocorticoid binding. Scatchard analysis indicated that the 30 and 300 fM doses of hurIL-1 significantly decreased the Bmax (maximum number of available binding sites), but did not alter the Kd (affinity of the glucocorticoid receptor for ligand). The decrease in cytosolic glucocorticoid binding, expressed relative to cytosol protein, did not result from increased intracellular protein in hurIL-1-treated RHC. In addition, the receptor binding reaction in RHC treated with 300 fM hurIL-1 could be resolved only by computer application of a three-parameter model. Sucrose density gradient ultracentrifugation analysis confirmed significantly less untransformed (8 to 10S) receptor-ligand complexes in hurIL-1-treated RHC, which is biologically significant because hurIL-1 (300 fM) also inhibited the glucocorticoid induction of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK). Altered transformation of the receptor-ligand complex, a possible mechanism of action for hurIL-1-mediated inhibition of PEPCK induction, was examined. However, receptor transformation, verified by in vitro activation by high salt (0.3 M KCl) of glucocorticoid receptor-ligand complexes and subsequent sucrose density gradient ultracentrifugation analysis, was not affected by hurIL-1. Furthermore, cytoplasmic glucocorticoid binding, determined in intact cell dexamethasone uptake experiments, was decreased in hurIL-1-treated RHC. The decrease in cytoplasmic glucocorticoid binding was reflected subsequently in decreased nuclear binding. The results support our hypothesis that, during acute infection and inflammation, mediators alter metabolic pathways in the liver by interfering with glucocorticoid action.
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PMID:Human recombinant IL-1 alters glucocorticoid receptor function in Reuber hepatoma cells. 284 96

Employing Reuber rat hepatoma cells, H4-II-E, the effects of aflatoxin B1 (AFB1) and sterigmatocystin (STC), which exhibit a similar cytotoxicity but a marked difference in hepatocarcinogenicity, on the hormonal induction of tyrosine aminotransferase (TAT), on glucocorticoid receptors, and on their nuclear acceptor sites were investigated. AFB1 strongly inhibited hydrocortisone-inducible TAT activity. The IC50 value was 0.2 micrograms/ml. AFB1 also showed weak inhibitory effects on insulin- and dibutyryl cyclic AMP-inducible TAT activities. In contrast, the IC50 of STC on hydrocortisone-inducible TAT activity was 3.5 micrograms/ml, about 10 times higher than that of AFB1. Dibutyryl cyclic AMP- and insulin-inductions were not depressed by STC. AFB1 inhibited the formation of cytosolic glucocorticoid receptor-hormone complexes (GRCs) but STC did not. Moreover, AFB1, activated in vitro by the microsomal cytochrome P-450 system, interfered more markedly in the formation of cytosolic GRCs than STC did. Sucrose density gradient analysis of GRCs and Scatchard analysis revealed that AFB1 and STC mainly impaired glucocorticoid receptors and GRC-acceptor sites, respectively. The present data suggest a marked difference between AFB1 and STC with regard to the inhibition of hormonal induction of liver specific enzymes.
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PMID:Modulation of hormonal induction of tyrosine aminotransferase and glucocorticoid receptors by aflatoxin B1 and sterigmatocystin in Reuber hepatoma cells. 290 Jun 79

Human hepatoma (Hep G2) cells were shown to synthesize and secrete a novel T4-binding protein, called 27K protein for its apparent mol wt on sodium dodecyl sulfatepolyacrylamide gel electrophoresis. The mRNA coding for this protein was characterized by immunoprecipitation of [125I]T4 bound to 27K protein secreted into the medium of oocytes injected with total Hep G2 RNA. Sucrose gradient fractionation of RNA from Hep G2 cells showed that TBG mRNA and 27K mRNA had different sizes, indicating that TBG and 27K protein are two distinct proteins. In vitro translation of RNA in a rabbit reticulocyte lysate demonstrated that the translation product immunoprecipitated by anti-27K serum had the same mol wt as the immunoprecipitated protein from whole cells labeled with [35S]methionine, thus suggesting that 27K protein is neither derived from TBG nor synthesized through a larger mol wt precursor, and also that it does not contain carbohydrates. The absence of carbohydrates was further supported by the observation that [3H]mannose was not covalently bound to the 27K protein when Hep G2 cells were labeled with [3H]mannose, nor was there a shift in apparent mol wt when the cells were treated with the glycosylation inhibitor tunicamycin. The kinetics of secretion of 27K protein were similar to those of albumin and faster than those of TBG, which is also in keeping with the nonglycoprotein nature of 27K protein.
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PMID:Biosynthesis of a novel thyroxine-binding protein (27K protein) in human hepatoma (Hep G2) cells. 300 58

The poly(A) tract found in eukaryotic mRNA was used to study methylation in mRNA obtained from Novikoff hepatoma cells. Methyl labeling of RNA was achieved with L-[methyl-(3)H]methionine under conditions that suppress radioactive incorporation into the purine ring. RNA that contains a poly(A) segment was obtained from polysomal RNA by chromatography on oligo(dT)-cellulose. Sucrose density gradient centrifugation of this RNA revealed a pattern expected for mRNA. The composition of the methyl-labeled nucleosides in the RNA was analyzed after complete enzymatic degradation to nucleosides. By use of DEAE-cellulose (borate) chromatography, which separates 2'-O-methylnucleosides from normal and base-methylated nucleosides, about 50% of the radioactivity was recovered in the 2'-O-methylnucleoside fraction and 50% in the base-methylnucleoside fraction. High-speed liquid chromatography (Aminex A-5) of the 2'-O-methylnucleoside fraction produced four peaks coincident with the four 2'-O-methylnucleoside standards. Analysis of the base-methylnucleoside fraction revealed a unique pattern. While ribosomal RNA and tRNA possessed complex base-methylnucleoside patterns, the distribution in mRNA was quite simple, consisting predominantly of N(6)-methyladenosine. These results demonstrate a unique distribution of methylated nucleosides in mRNA. By analogy to ribosomal RNA synthesis, the presence of methylnucleosides in mRNA may reflect a cellular mechanism for the selective processing of certain mRNA sequences.
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PMID:Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. 437 99

The interaction between antibodies directed against RNA polymerase I purified from Morris hepatoma 3924A and homologous RNA polymerase II was investigated. The activity of partially purified polymerase II was inhibited by the antibodies. In contrast, the reaction catalyzed by the purified enzyme was not affected. Partially purified polymerase II preparations contained a protein kinase activity. Sucrose gradient centrifugation in the presence of 0.3 M KCl resulted in complete separation of RNA polymerase II from protein kinase as well as in complete loss of sensitivity to the anti-RNA polymerase I antibodies. The protein kinase possessed reaction characteristics similar to those of the NII protein kinase (Rose, K.M., Bell, L.E., Siefken, D.A. and Jacob, S.T. (1981) J. Biol. Chem. 256, 7468-7477) which is associated with hepatoma RNA polymerase I (Rose, K.M., Stetler, D.A. and Jacob, S.T. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 2833-2837). The activities of both kinases were inhibited to the same extent by anti-RNA polymerase I antibodies and polypeptides of Mr 42 000 and 25 000, present in both kinase preparations, formed immune complexes with the antisera. Readdition of protein kinase NII to purified polymerase II resulted in phosphorylation of the polymerase and a concomitant enhancement of RNA synthesis. After addition of the kinase, RNA polymerase II activity was again sensitive to anti-RNA polymerase I antibodies. Upon reacting with protein kinase NII, RNA polymerase II polypeptides could be detected in immune complexes with anti-RNA polymerase I antibodies. These data indicate that protein kinase NII is associated with RNA polymerase II during early stages of purification and is at least partially responsible for the immunological cross-reactivity of RNA polymerases I and II.
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PMID:Protein kinase NII. Interaction with RNA polymerase II and contribution to immunological cross-reactivity of RNA polymerases I and II. 618 63


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