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)

Phosphoenolpyruvate carboxykinase (GTP) was induced by a combination of dibutyryl cyclic AMP, theophyline and dexamethasone in Reuber H35 hepatoma cells under conditions where an amino acid in the medium was replaced by an appropriate analogue. 2. With canavanine replacing arginine or with 5-fluorotryptophan or 6-fluorotryptophan replacing tryptophan the induced enzyme had a lower catalytic activity-relative to antibody reactivity. 3. These aberrant enzyme molecules were heat-labile in vitro. 4. Measurements of enzyme degradation in vivo indicated that the canavanine-containing enzyme and the 6-fluorotryptophan-containing enzyme were degraded more rapidly than the enzyme containing all natural amino acids.
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PMID:Properties of phosphoenolpyruvate carboxykinase (guanosine triphosphate) synthesized in hepatoma cells in the presence of amino acid analogues. 16 22

Ornithine decarboxylase has been induced in log phase hepatoma cells grown in suspension culture. Induction with N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphate produced a 4-fold increase in enzyme activity by 3 hours which was followed by a return to base levels by 6 hours. Induction with dexamethasone, a potent synthetic glucocorticoid, exhibited a slow steady rate of increase in enzyme activity, reaching a plateau level of approximately 5- to 6-fold stimulation by about 12 hours. Induced cell and regenerating rat liver ornithine decarboxylase were shown to be indistinguishable by titration with antibody monospecific to the latter and by heat stability. L-[14C]Leucine incorporation into immunoprecipitable enzyme protein after induction in vitro or partial hepatectomy showed an increase which, when coupled with the increase in enzymatic activity, indicated de novo synthesis of enzyme protein. Physiological concentrations of the naturally occurring polyamines, spermidine and spermine, abolish cyclic AMP induction whereas they have no effect on dexamethasone induction. Both inductions were abolished by cycloheximide; in contrast, inhibition by actinomycin D was complete for dexamethasone induction and only partial with respect to cyclic AMP induction. The different time pattern of induction seen with cyclic AMP and dexamethasone, the partial inhibition of the cyclic AMP induction seen with actinomycin D, as well as the absence of inhibition of the dexamethasone induction by polyamines, indicate that these inducers might affect different aspects of the control of the same enzyme.
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PMID:Stimulation of ornithine decarboxylase synthesis and its control by polyamines in regenerating rat liver and cultured rat hepatoma cells. 18 26

Smooth and rough endoplasmic reticulum from rat liver and hepatomas exhibited endogenous protein kinase activity independent of adenosine 3':5'-monophosphate. The phosphorylation of smooth membranes by this process was consistently higher than that of rough membranes. When histone was added along with the smooth endoplasmic reticulum, cyclic AMP stimulated protein phosphorylation. Analysis of membrane-phosphorylated proteins by gel electrophoresis showed 5 major phosphorylated bands with estimated molecular weights of 155 000, 62 000, 50 000, 46 000 and 43 000, whereas major bands having estimated molecular weights of 62 000, 50 000 and 43 000 were found in membranes of the smooth endoplasmic reticulum of the Morris hepatoma 5123 C. Since previous studies in this and other laboratories have demonstrated the similarity of the protein components of membranes of the endoplasmic reticulum of normal liver and hepatoma, our findings indicate an inability of the protein kinase of hepatoma intracellular membranes to phosphorylate protein species that are found in membranes of both liver and the neoplasm.
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PMID:Protein phosphorylation of the smooth and rough endoplasmic reticulum in normal and neoplastic liver of the rat. 18 Dec 47

The incorporation of [3H]adenosine, [3H]adenine, and [3H]hypoxanthine into adenine nucleotides of nude (athymic) mouse liver and human hepatoma grown subcutaneously in nude mice was studied. 3H and 32P radioactive labeling in vivo of acid-soluble nucleotides followed by chromatographic procedures indicated that, in contrast to [3H]adenine and [3H]hypoxanthine, [3H]adenosine is preferentially incorporated into ATP in comparison with its incorporation into AMP and ADP. This phenomenon, as well as complementing the recently reported 3-fold increase in total cellular ATP upon treatmen- with 0.5-1.0 mM concentrations of adenosine, indicates the formation from adenosine of compartmentalized ATP that is not produced from either adenine or hypoxanthine. The observed effect is of larger magnitude in the growth-arrested normal liver than in the actively growing tumor.
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PMID:Incorporation of adenosine into ATP: formation of compartmentalized ATP. 18 61

1,4,5,6,8-Pentaazaacenaphthylene-3-amino-1,5-dihydro-5-methyl-(5-14C)-1-beta-D-ribofuranysly (NSC-154020), a tricyclic 7-deazapurine nucleoside (TCN), was rapidly incorporated into the acid-soluble pool by cultured Novikoff rat hepatoma cells, mouse L-cells, HeLa cells, and HEp-2 cells, but little incorporation into nucleic acids occurred. More than 90% of the intracellular radioactivity was associated with the monophosphate (MP) of the substrate concentration followed normal Michaelis-Menten kinetics. Comparison of the kinetic constants for the uptake of adenosine and the TCN and of the inhibition of their uptake by each other suggests that both were transported by the same system (Michaelis constant approximately 6-10 muM) and with about the same efficiency. The TCN was also phosphorylated in a cellfree extract containing adenosine kinase activity at about the same rate as was adenosine, but not further phosphorylation of the analogue MP occurred. No significant deamination or degradation of the adenosine analogue to its base and ribose-1-phosphate was observed. TCN inhibited the replication of all four types of cells propagated in suspension culture; however, Novikoff cells were several times more sensitive than were the other three cell types, despite the finding that the TCN-MP, probably the main toxic principle, accumulated to about the same concentration in cells of all four lines. Complete inhibition of replication of Novikoff cells were several times more sensitive than were the other three cell types, despite the finding that the TCN-MP, probably the main toxic principle, accumulated to about the same concentration in cells of all four lines. Complete inhibition of replication of Novikoff cells and cell death occurred at concentration as low as 15 muM TCN. At these concentrations, TCN, within 2 hours of its addition, completely inhibited the incorporation of [14C]formate int0 nucleotides and nucleic acids of Novikoff cells. An inhibition of the denovo synthesis of purine and pyrimidines, however, was not the only toxic effect of the TCN since high concentrations of uridine, adenine, guanine, and hypoxanthine, either alone or combined, failed to prevent the inhibition of cell replication by TCN. Also, between 1 and 3 hours of treatment, 70-80% of the Novikoff cells fragmented into four to eight vesicles per cell. These fragments were impermeable to trypan blue, still exhibited some metabolic activity such as the phosphorylation of AMP and TCN, but failed to replicate when the drug was removed. No similar fragmentation was observed with the other cell lines. Novikoff and L-cells rapidly released TCN-MP into the culture fluid. After 4 hours of incubation, 70-100% of the total radioactivity in the medium was associated with the MP. Only a little TCN-MP was released from HeLa and HEp-2 cells. A TCN-resistant mutant of Novikoff cells failed to phosphorylate the analogue and was deficient in adenosine kinase.
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PMID:Transport, phosphorylation, and toxicity of a tricyclic nucleoside in cultured Novikoff rat hepatoma cells and other cell lines and relase of its monophosphate by the cells. 18 99

Plasma membranes from rat liver were found to contain at least two types of specific binding sites for cyclic [3H] adenosine 3', 5'-monophosphate (c[3H]AMP) with apparent dissociation constants of 0.51 +/- 0.14 and 2.9 +/- 0.6 nM (O degrees), respectively. The levels of these binding sites in liver plasma membranes were about 0.60 +/- 0.20 and 1.3 +/- 0.5 pmole/mg protein. The highest affinity binders for c[3H]AMP were found to be reduced in amount in plasma membranes of ascites hepatomas to 1/3 to 1/4 as compared with liver membranes in the cases of AH-130 and AH-7974 and to an almost undetectable level in the case of AH-130F(N). No difference in the endogenous phosphorylation of plasma membranes by (gamma-32P])ATP was, however, detected among liver and hepatoma plasma membranes. Addition of cAMP or cGMP at various concentrations did not affect the endogenous phosphorylation of plasma membranes of these cells.
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PMID:High affinity binders for cyclic adenosine 3', 5'-monophosphate on plasma membranes isolated from rat liver and ascites hepatomas. 18 3

The studies are presented which demonstrate that smooth endoplasmic membrane of normal liver has a single apparent binding site for cAMP with a KD of 0.6 X 10(-8) M. In contrast to this, however, cyclic AMP binding to the intracellular membrane of hepatoma 7800 exhibit two binding sites; the binding constant of one site on the tumor membrane is comparable to that of the normal liver whereas the value of the second intrinsic association constant differ by a factor of 10. It is suggested that there may be an association between abnormal cyclic nucleotide metabolism and the intracellular membrane modulation of the expression of genetic information in normal and neoplastic cells.
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PMID:Cyclin nucleotide binding sites of the smooth endoplasmic reticulum from normal and neoplastic liver in the rat. 18 1

Fractions of heavy and light mitochondria are isolated from homogenates of homologous rat tissues (intact liver, regenerating liver within 24 hours after hepatectomy and 27 hepatoma) by means of differential centrifugation. It is found that tumour mitochondria have higher heterogeneity and lower buyoant density than mitochondria from normal hepatocytes. The activity of two enzymes of DNA precursors synthesis (ribonucleotide reductase and thymidine kinase) in subcellular fractions is demonstrated to correlate with the tissue growth rate. A single injection of cyclic AMP into hepatectomised rats resulted in the retardation of the regeneration process, and the activity of both enzymes reached its normal level in all the fractions studied after 24 hours after the operation. Thymidine kinase and ribonucleotide reductase are located mainly in the mitochondrial matrix, however, pronounced enzyme activity is observed also in membrane fractions. The activity of the enzymes in the fraction of external mitochondria membranes in rapidly growing tissues is 2--3 times as high as in the same fraction from normal rat liver.
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PMID:[Mitochondrial thymidine kinase and ribonucleotide reductase from rat liver and rat hepatoma 27]. 19 36

Normal expression of a variety of hormonal effects which depend on cyclic AMP (adenosine 3':5'-monophosphate) requires the presence of glucocorticoids. Our hypothesis was that glucocorticoids control directly or indirectly the activity of cyclic-AMP-dependent protein kinase. This has been investigated in cultured hepatoma (HTC) cells in which N6,O2'-dibutyryladenosine 3':5'-monophosphate increases the activity of tyrosine transaminase only after glucocorticoid treatment. In these cells, we have determined the concentration and half-life of protein kinase, the sensitivity of this enzyme in vitro to cyclic AMP and to its thermostable protein inhibitor, the state of dissociation of protein kinase holoenzyme in vivo and its sensitivity, in the intact cell, to dibutyryladenosine 3':5'-monophosphate and to the inhibitor diamide, and we have also determined the concentration of endogenous thermostable protein inhibitor of protein kinase. None of these parameters were influenced by glucocorticoids under conditions where these hormones stimulate the activity of tyrosine transaminase and restore sensitivity to dibutyryladenosine 3':5'-monophosphate. It is concluded that the permissive action of glucocorticoids probably results from a control of cyclic-AMP-dependent processes exerted at a level beyond the protein kinase system.
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PMID:Activity of protein kinase dependent on adenosine 3':5'-monophosphate and of its thermostable protein inhibitor in rat hepatoma (HTC) cells. Unlikely role in the permissive action of glucocorticoids. 19 14

The authors report the results of separate determination of the concentration of free adenine nucleotides (ATP, ADP, AMP) in tumors, intact animals liver, and tumor-bearing animals liver. In Zajdela ascites hepatoma, ascites tumor NKly and solid lymphosarcoma, solid hepatomas 46 and 22 A the amount of ATP and ADP was found to be markedly reduced compared with their content in the liver. The ratio ATP/ADP is increased in ascites cells of tumor NKly, Zaidela hepatoma and lymphosarcoma and is decreased in solid hepatoma 46 and 22 A. Cell energy potential, calculated on the basis of ATP ratio to a sum of adenine-nucleotides, is also increased in ascites cells of tumor NKly, Zaidela hepatoma and is diminished or remains unchanged in hepatoma 46 or 22A. Cell energy charge is increased in tumor NKly, Zajdela hepatoma, lymphosarcoma and is decreased in solid hepatoma 46 and 22A.
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PMID:[Content of the components of the adenylic acid system in solid and ascitic tumors in the liver of experimental animals]. 19 12


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