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)

Starvation of the mouse hepatoma cell line Hepa for an essential amino acid (Trp, His, Leu, Ile or Phe) stimulated the incorporation of [3H]adenosine as ADP-ribose monomer into an 80,000-Mr protein, P80. Two-dimensional electrophoresis of Hepa proteins showed that P80 was the only protein labeled under starvation conditions. Time course experiments showed that the ADP-ribosylation of P80 was a consequence rather than the cause of reduced translational activity. Cycloheximide treatment and incubation at reduced temperatures also reduced the rate of protein synthesis and stimulated the ADP-ribosylation of P80. Starvation-dependent ADP-ribosylation of P80 was shown to occur in three other cell lines (Chang, Neuro-2a, and chick comb fibroblasts).
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PMID:Translational control of ADP-ribosylation in eucaryotic cells. 379 12

Cell growth using homocysteine as a source of cysteine-sulphur requires two enzymes, cystathionine synthase (CS) and gamma-cystathionase (CT). The second of these enzymes, CT, is apparently present in most cell lines regardless of their tissues of origin, since most cells can grow in vitro in the absence of cystine if they are provided with cystathionine, the intermediate in the pathway. Likewise, homocysteine will support the growth of many human cells. However, of a wide range of rodent cells, only well-differentiated rat hepatoma cells were found to grow using homocysteine in place of cystine. It is shown that cell growth in homocysteine-medium correlates well with the presence in the cells of detectable levels of CS. Furthermore, in cells able to grow in homocysteine-medium, it is possible to demonstrate the homocysteine-dependent trans-sulphuration of serine to cysteine. Growth in homocysteine-medium is not dependent on the release of preformed cysteine from disulphide complexes with serum proteins. In cell hybrids, and in 'dedifferentiated' variants of rat hepatomas, CS, but not CT, is subject to extinction coordinately with well-characterized liver-specific traits. For rodent cells, homocysteine-medium thus acts as a selective medium requiring the expression of a single liver-specific trait, CS. In addition it is shown that, in certain hepatoma variants, CS is regulated co-ordinately with a urea-cycle enzyme (carbamoyl phosphate synthetase I) by glucocorticoids and cyclic-AMP. Cell death through cysteine starvation is briefly considered. The immediate cause of death is apparently an insufficient supply of reduced glutathione. Selenium and vitamin E assist cell growth when the supply of cysteine is limiting.
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PMID:Characterization of cystathionine synthase as a selectable, liver-specific trait in rat hepatomas. 379 84

1. The activity of l-asparaginase was very low in the liver of newborn rats and mice, and increased within a few days of birth. 2. In rats, but not in mice, the enzyme activity was higher in females than in males, was enhanced by administration of oestradiol, and was decreased by gonadectomy. 3. The enzyme activity decreased in mice starved or fed on a low-protein diet; in rats it was enhanced by starvation, by feeding them on a high-protein diet, or by administration of l-asparagine. 4. The asparaginase activity was decreased in regenerating liver, and was almost absent in the Morris hepatoma 5123.
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PMID:The regulation of L-asparaginase activity in rats and mice. Effects of normal and malignant growth, of sex and of dietary changes. 431 Oct 65

Induction of L-tyrosine:2-oxoglutarate aminotransferase (EC 2.6.1.5) by N6,O2'-dibutyryl-adenosine 3',5'-monophosphate (Bt2cAMP) in Reuber H35 hepatoma cells reaches a maximum value between 3-5 h after addition of Bt2cAMP and subsequently decreases in the continuous presence of Bt2cAMP. We have investigated the kinetics of the increase, i.e. induction, and the decrease, i.e. the repressed state, of the tyrosine-aminotransferase-synthesizing system under these conditions. Our experimental results are as follows. 1. The repressed state of the tyrosine-aminotransferase-synthesizing system is not caused by a decrease in the intracellular cAMP concentration. 2. The repressed state is inhibited by actinomycin D (while induction is not inhibited). 3. During the repressed state no effect of dexamethasone on tyrosine aminotransferase synthesis is found, while during induction Bt2cAMP and dexamethasone act synergistically. 4. Longer starvation of the cells in serum-free medium has no influence on the kinetics of the induction/repressed state curve. From these results we have concluded that the mechanism of the transition to the repressed state of the tyrosine-aminotransferase-synthesizing system is essentially different from the mechanism of deinduction which occurs after removal of the inducer. Moreover, the repressed state of the system is a phenomenon which is induced by Bt2cAMP separately from induction at a different level of protein synthesis.
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PMID:Positive and negative cAMP-mediated control of tyrosine aminotransferase synthesis in Reuber H35 hepatoma cells. 612 6

The behavior of the activities of GMP synthetase (xanthosine-5'-phosphate: L-glutamine amino-ligase(AMP-forming),EC 6.3.5.2) and GMP kinase (ATP: (d)GMP phosphotransferase,EC 2.7.4.8) was elucidated in cytosol preparations of rat tissues, including fetal, neonatal and regenerating liver, in a transplantable kidney tumor, and in a spectrum of 11 hepatomas of different growth rates. GMP kinase activity was 60-fold or more higher than GMP synthetase activity in all of the examined tissues. GMP synthetase activity was increased in all hepatomas and in the kidney tumor, compared to control tissues, reaching 5.5-fold the normal liver values in the most rapidly growing hepatoma. This increase correlated with the tumor growth rates. GMP kinase activity showed no consistent pattern of alteration in the tumors. In both fetal and neonatal rat liver the activity of GMP synthetase was 2.5-times higher than in livers of adult rats, but GMP kinase activity did not change markedly during liver development. After partial hepatectomy GMP synthetase activity was elevated, reaching a peak of 155% of the sham-operated control values by 36 h after the operation. GMP kinase activity was not affected by partial hepatectomy. After 3 days starvation hepatic GMP kinase activity decreased slightly faster than total cytosol protein, while GMP synthetase activity was preferentially maintained. These results indicate that GMP synthetase activity was linked with cellular proliferation in differentiating, regenerating and neoplastic tissues.
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PMID:Guanosine-5'-phosphate synthetase and guanosine-5'-phosphate kinase in rat hepatomas and kidney tumors. 626 Feb 5

Within minutes of glucose starvation confluent monolayers of rat hepatoma cells synthesize glycoproteins, including alpha 1-acid glycoprotein, which appear on two-dimensional gels as size heterogeneous spot series. The longer the period of glucose starvation the more the production of the glycoproteins is shifted toward smaller molecular weight forms. To compare these forms with the corresponding glycoproteins synthesized either in a cell-free system or by nonstarved cells, a mapping of the N-glycan was done by endo-beta-N-acetylglucosaminidase digestion within a polyacrylamide gel. Glycoproteins from glucose-starved cells contain a reduced number of N-glycans which belong to both the endo H-sensitive and resistant type. The decrease of N-glycosylation may be correlated with the accumulation of truncated lipid-bound oligosaccharides, for the gel chromatography of the oligosaccharides released from the lipid and protein fractions of glucose-starved cells revealed a drastic reduction in their size. Most of the lipid-linked oligosaccharides synthesized during glucose starvation are resistant to endo H digestion. Under conditions of limiting glycosylation we were able to show by glycopeptide analysis, that in the case of alpha 1-acid glycoprotein, N-glycans are added randomly to the 6 possible N-glycosylation sites. Furthermore, non- or partially N-glycosylated proteins do not acquire additional oligosaccharide units after restoration of glucose although the proteins can undergo secondary modification and, in the case of the secretory proteins, can be exported.
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PMID:Glucose starvation leads in rat hepatoma cells to partially N-glycosylated glycoproteins including alpha 1-acid glycoproteins. Identification by endoglycolytic digestions in polyacrylamide gels. 640 21

To elucidate the recently advanced hypothesis that glutathione [L-gamma-glutamyl-L-cysteinyl glycine (GSH)] regulates deiodinating enzyme activities, accounting for the decreased conversion of T4 to T3 in the liver of fetal and starved animals, we investigated thyroid hormone metabolism in GSH-depleted neoplastic and normal hepatocytes. In monkey hepatocarcinoma cells, intracellular total GSH decreased below 10% of the control value (approximately 25 micrograms/mg protein) when cells were grown for 44 h in medium deficient in cystine and methionine or in cystine alone. The latter finding indicated that transsulfuration from methionine to cysteine was defective in these neoplastic cells. In primary cultured adult rat hepatocytes, on the other hand, the transsulfuration pathway was intact, and total GSH decreased below 10% of control (approximately 20 micrograms/mg protein) only in cells grown in cystine- and methionine-deficient medium. In both cell types, the oxidized GSH fraction remained constant (2-5% of total). Incubation with 125I-labeled T4 and T3, followed by chromatography, was used to evaluate 5-deiodination in hepatocarcinoma cells and both 5- and 5'-deiodination in normal hepatocytes. Deiodination was not decreased by GSH deficiency in either case, but was actually increased in hepatocarcinoma cells. This resulted from an increase in the Vmax of 5-deiodinase related to growth arrest. Diamide at 2 mM reversibly inhibited both 5'- and 5'-deiodination in rat hepatocytes, accompanied by decreased total GSH as well as increased GSH disulfide (27% of total). The data suggest that GSH is so abundant in the liver that hepatocytes can tolerate a greater than 90% decrease in intracellular concentration without any change in thyroid hormone deiodination and indicate that altered thyroid hormone metabolism in the fetus and in starvation cannot be accounted for by a decreased hepatic GSH concentration.
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PMID:Glutathione deficiency induced by cystine and/or methionine deprivation does not affect thyroid hormone deiodination in cultured rat hepatocytes and monkey hepatocarcinoma cells. 679 Feb 65

In the cultured hepatoma cell HTC, amino acid starvation stimulated both influx and efflux of 2-(methylamino)isobutyric acid (MeAIB) across the plasma membrane with little effect on the ultimate cellular accumulation of this amino acid. In agreement, prior amino acid starvation had little effect on the cellular steady state levels reached for various natural amino acids during subsequent incubation in an amino acid-rich medium containing cycloheximide. Furthermore, efflux of [14C]MeAIB was markedly increased by amino acid starvation. These findings do not mean that adaptive regulation of neutral amino acid transport is pointless. If membrane transport rather than metabolism is the rate-limiting step for net amino acid production or consumption, or becomes so during times of elevated formation or catabolism of an amino acid, then proportionate changes of both the opposed fluxes should enhance its net generation or consumption. Amino acid starvation enhances MeAIB-dependent Na+ influx. Alteration of the external [Na+] changes the Km, not the Vmax, for MeAIB influx when the degree of System A derepression is stabilized with cycloheximide. In both starved and unstarved cells, Km/Vmax for MeAIB entry yields a linear function with the reciprocal of the external [Na+], supporting at least for influx a rapid equilibrium-ordered kinetic model in which Na+ binds to the carrier site before the amino acid. Elevated cellular [Na+] obtained by ouabain treatment increased MeAIB efflux in parallel. Trans-inhibition of MeAIB influx by accumulated MeAIB, and as a related phenomenon by cellular Na+, was as effective in unstarved as in starved cells, showing independence of this kinetic phenomenon from adaptive regulation. The decreased MeAIB accumulation resulting from decreased influx and increased efflux occurring at high internal [Na+] applies both to unstarved and starved cells. We conclude that cellular Na+ accumulations, produced by increasing levels of ouabain, reversibly reduce the ability of MeAIB to repress System A because its interior concentration is prevented from rising, although transport in both directions continues; accordingly, the repressive signal appears to come from the internal amino acid levels rather than from occupation of the carrier site for System A flux.
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PMID:Simultaneous regulation of amino acid influx and efflux by system A in the hepatoma cell HTC. Ouabain simulates the starvation-induced derepression of system A amino acid transport. 686 76

A line or rat hepatoma cells in culture which, in response to serum starvation, become arrested in the early G1 phase of growth, can be stimulated by insulin alone to enter the cell cycle and traverse S phase. A half-maximum response is observed at 30 to 70 picomolar concentrations and the maximum response is essentially identical to that found with optimum serum concentrations.
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PMID:Insulin as a potent, specific growth factor in a rat hepatoma cell line. 700 95

Stimulation of System N transport of glutamine by amino acid starvation of the rat hepatocyte can be repressed by one of its substrates, histidine, but not by two others, glutamine or asparagine. Furthermore, 2-(methylamino)isobutyric acid is also repressive, although it is not perceptibly a substrate or inhibitor of that system. The repression of System A by glutamine proves in contrast not to be dissociated from transport: relatively slow System A uptake of glutamine has now been shown in this cell. System A transport of glutamine is conspicuous in the hepatoma cell HTC and is increased after amino acid starvation of both hepatocytes and the hepatoma cells. Differential repression of the systems could be shown, although lowering the pH prevented the derepression of one system as much as the other on amino acid starvation.
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PMID:Incomplete correspondence between repressive and substrate action by amino acids on transport systems A and N in monolayered rat hepatocytes. 705 75


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