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)

Enzyme deviations in injured livers were studied by analyzing isozyme patterns of phosphorylase using a newly developed electrophoretic method, which separates six molecular species of this enzyme, i.e. M,FM,F,L,L', and FL'. In hepatic injuries caused by CCl4 and galactosamine intoxications of rats, F appeared in early stages and L' (and FL') in later stages of the injuries with a concurrent decrease or loss of L, which is a sole isozyme component of adult liver. In injured livers of patients with hepatitis and cirrhosis of the liver, increases in FL' activity were also found. Appearance of F was found only in hepatocellular carcinoma. The results obtained with phosphorylase isozyme analysis support the idea that an undifferentiated gene expression takes place in the injured livers of non-malignant hepatic disorders.
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PMID:Studies of liver phosphorylase in hepatic injuries II. Alteration in isozyme pattern. 15 93

Incorporation of uracil and uridine into ribonucleic acid (RNA) was compared among the ascitic and solid forms of Ehrlich mouse tumor, Morris hepatoma, Rhodamine sarcoma, gastric cancer and ulcer from human patients, and several normal rat tissues. Of these cells tested, the cells of Ehrlich ascites and solid tumors, human gastric cancer and ulcer, and certain tissues of a normal rat showed a considerably high activity. Furthermore, Ehrlich ascites tumor cells indicating a high incorporation activity was also high in activities of both phosphorylase and kinase for uridine, while Rhodamine sarcoma as a representative having a low incorporation activity was considerably low in these two enzymic activities. RNA synthesis from uridine phosphates by Rhodamine sarcoma was maintained to a fairly high extent contrary to its low activities of the phosphorylase and the kinase. Consequently, the low utilization of uracil and uridine by certain tumors was suggested to be due to the extremely low activities of both enzymes.
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PMID:Incorporation characteristics of uracil, uridine, and orotic acid into ribonucleic acid of neoplastic cells. 19 18

Glycogen accumulation in growing cultures of ZHC cells (originally derived from the Zajdela ascitic hepatoma) is accompanied by an increase in glycogen synthetase (E.C. 2.4.1.11) and phosphorylase (E.C. 2.4.1.1) activities. Essentially the synthetase b and the phosphorylase a are involved in this process. The glycogen accumulation in ZHC cells us preceeded by a noticeable peak of cAMP, whereas cGMP rises early after replating and then decreases simultaneously with the growth rate. The present results suggest that these cultured hepatoma cells undergo throughout every passage an induction process involved in glycogen synthesis storage. Since the original ascites cells growing in vivo (which lack glycogen) and the cultured ZHC cells exhibit similar glycogen synthetase and phosphorylase activities, the resurgence of the glycogenic function (Staedel and Beck, 1978) in the in vitro cultureed cells does not seem related to a change in these two enzymes. By contrast, the high cyclic nucleotide levels in the cultured cells, as compared to those in the ascites cells, offer a possible explanation.
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PMID:Modifications of the activities of key enzymes and intracellular levels of cyclic nucleotides, in correlation with the glyogen deposition in a cultured hepatoma cell line. 22 82

Glycogen phosphorylase isoenzymes were isolated from normal rat liver, rat brain, the glycogen-poor Morris hepatoma (MH) 3924A, and the glycogen-rich non-tumorigenic liver cell line C1I. Electrophoretic and immunological characterization of the enzymes showed that tumour and C1I cells expressed a phosphorylase isoform similar to the brain type; the liver type was not detectable. All enzymes were obtained as dimers; the Mr of the subunits was 96,000 (liver), 93,000 (brain and MH 3924A) and 92,000 (C1I). Isoelectric focusing revealed a main band of pI 6.34 for liver phosphorylase a, pI 5.67 for the enzymes from MH 3924A and brain, and pI 5.68 for C1I phosphorylase. Partial kinetic characterization of the AMP-independent forms of the isoenzymes yielded Km values for glucose 1-phosphate of 3.5 +/- 0.5 mM (liver), 3.9 mM (brain), 1.9 +/- 0.3 mM (MH 3924A) and 2.5 +/- 0.5 mM (C1I); Km values for glycogen were 0.4 mM (liver) and 0.3 mM (MH 3924A and C1I), calculated as glucose equivalents. The AMP-independent phosphorylase was inhibited by glucose 6-phosphate (Glc6P) with Ki values of 0.32 +/- 0.03 mM (C1I), 0.50 +/- 0.04 mM (MH 3924A) and approximately 5 mM (brain). The inhibition could be abolished by 1 mM-AMP, indicating that AMP and Glc6P may partially compete for the same site on the protein. Liver phosphorylase a was not inhibited by up to 25 mM-Glc6P. In contrast with liver and brain isoenzymes, phosphorylase from the cell lines was not affected by NaF and Na2SO4. The data show that both the hepatocellular carcinoma and the non-malignant immortalized liver cells express a phosphorylase isoform different from the liver type. Furthermore, there is some evidence that the enzyme from MH 3924A and C1I cells is distinct from brain phosphorylase a, in spite of electrophoretic and immunological resemblance, and that this isoenzyme is subject to altered metabolic regulation.
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PMID:Glycogen phosphorylase isoenzymes from hepatoma 3924A and from a non-tumorigenic liver cell line. Comparison with the liver and brain enzymes. 155 49

Homogeneous (7.5%) and gradient (10-15%) ultrathin nondenaturating miniaturized polyacrylamide gels (Pharmacia PhastGel media) were used to separate glycogen phosphorylase isoforms from rabbit muscle, rat liver and brain, MH 3924A cells, a dedifferentiated hepatocellular carcinoma of the rat, and C1I cells, a nontumorigenic epithelial rat liver cell line. The enzymes were detected by in situ phosphorylase assay and by immunoblotting. Phosphorylase proteins from the brain, MH 3924A, and C1I exhibited similar electrophoretic mobility, which was different from that of the enzymes from the muscle and normal liver. Molecular weight determination from sodium dodecyl sulfate gels yielded similar data for the subunits of muscle and liver enzymes (98,000 and 96,000), respectively, on one hand, and brain, MH 3924A tumor, and nontumorigenic C1I cells (93,000, 93,000 and 92,000), respectively, on the other. In the native gels the enzymes migrated as dimers: for muscle phosphorylase a, a tetramer was also observed. The a and b forms of the enzymes could not be resolved. An antibody raised against rat liver phosphorylase reacted only with the liver enzyme, whereas an antibody raised against brain phosphorylase stained the brain enzyme and the enzymes from MH 3924A and C1I cells. This indicates that hepatoma cells and immortalized nontumorigenic epithelial liver cells express a phosphorylase isoenzyme that is different from the liver type but similar to the brain type. The PhastSystem provides a rapid, sensitive, and highly reproducible method to resolve the different isoenzymes of glycogen phosphorylase.
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PMID:Resolution of glycogen phosphorylase isoenzymes in precast PhastSystem polyacrylamide gels. 207 Jul 85

In the course of investigating the neoplastic alterations of protein phosphatases, the particulate fractions of rat liver and AH-13, a strain of rat ascites hepatoma, were chromatographed on DEAE-cellulose and assayed for protein phosphatase using glycogen synthase D and phosphorylase a as substrates. The synthase phosphatase activity of rapidly growing AH-13 was due almost entirely to a divalent cation-inhibited protein phosphatase, tentatively designated phosphatase N, the level of which was elevated remarkably in the hepatoma as compared with liver. Other hepatomas including primary hepatoma induced with 3'-methyl-4-dimethylaminoazobenzene also exhibited high levels of this phosphatase. Phosphatase N exhibited Mr = 49,000 (gel filtration) and has been partially purified with little alteration in properties. Partially purified phosphatase N was inhibited by divalent cations, rabbit skeletal muscle polypeptide inhibitor-2 and heparin, and released the catalytic subunit of type-1 protein phosphatase upon tryptic digestion. It is therefore apparent that phosphatase N is a type-1 protein phosphatase. There is some evidence to suggest that the high levels of phosphatase N in neoplastic cells are due primarily to enhanced synthesis of its non-catalytic (regulatory) subunit.
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PMID:Particulate-associated protein phosphatases of rat hepatomas as compared with the enzymes of rat liver. 215 61

The beta-adrenoceptor-cyclic adenosine monophosphate (AMP) dependent glycogenolytic cascade was examined in normal rat hepatocytes and rat ascites hepatoma AH130 cells. The cyclic AMP content in AH130 cells was half of that in normal hepatocytes, and the cyclic AMP levels in both kinds of cells were clearly increased by isoproterenol (IPN). Cyclic AMP-dependent protein kinase activity was higher in AH130 cells than in normal hepatocytes. Phosphorylase kinase activities in 10000 x g supernatant of normal hepatocytes and AH130 cells were also increased in the presence of cyclic AMP. Phosphorylase a activities in the supernatant of both kinds of cells gradually decreased during incubation with 40 mM glucose at 37 degrees C, and the enzyme activity of normal hepatocytes was completely restored by the addition of Mg2(+)-adenosine triphosphate (ATP), but in the case of the hepatoma cells the recovery was small. The decreased phosphorylase a activity in the hepatoma cells was increased by additional glycogen but did not exceed the level before the incubation. In the case of normal hepatocytes it was not affected by glycogen. This indicates that glycogen contained in the cells influences the activation of phosphorylase; the glycogen content in AH130 cells was far less than in normal hepatocytes. On the other hand, when intact cells were incubated with a high concentration of glucose, phosphorylase a activity in the homogenate of normal hepatocytes was decreased and could be restored by IPN and dibutyryl cyclic AMP, but the enzyme activity in the homogenate of AH130 cells was very low and hardly changed after the incubation and treatment with these agents.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies on responsiveness of hepatoma cells to catecholamines. V. Loss of adrenergic response of glycogen phosphorylase in rat ascites hepatoma AH130 cells. 233 60

Insulin alone at concentrations of less than 1 to 5 uU/ml increased the enzyme activities of glycogen synthase, synthase phosphatase, phosphorylase, and phosphorylase phosphatase in hepatoma H4 cells in culture in the presence and absence of serum. Increase in total and active forms of glycogen synthase and phosphorylase were observed. Cycloheximide blocked the action of insulin on glycogen synthase, glycogen synthase phosphatase and phosphorylase phosphatase. The enzymes with the exception of glycogen synthase phosphatase were expressed with greater hormonal sensitivity in the absence as compared to the presence of serum in terms of hormone concentration required and or time of onset. These results demonstrate that these glycogen metabolizing enzymes are under long term control by insulin, with glycogen synthase being the most sensitive of the enzymes studied to the action of the hormone.
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PMID:Long term regulation of glycogen metabolizing enzymes by insulin in H4 hepatoma cells. 304 Dec

Glycogen phosphorylase a activity in 7 rat ascites hepatoma cell lines treated with adrenergic agents, phenylephrine, epinephrine and isoproterenol, was investigated as compared with that in freshly isolated rat hepatocytes. Basal phosphorylase activities in hepatoma cells except AH7974 cells were lower than that in hepatocytes. Phosphorylase in hepatoma cells was not activated by any of the agents, while the enzyme activity in hepatocytes was clearly increased in a dose- and time-dependent manner. Phosphorylase in hepatocytes was sensitive to glucagon, but it was found to be insensitive to glucagon in all hepatoma cells. The present results suggest that rat ascites hepatoma cells may escape the glycogenolytic regulation by catecholamines and glucagon.
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PMID:Studies on responsiveness of hepatoma cells to catecholamines. IV. Lack of adrenergic activation of phosphorylase in rat ascites hepatoma cells. 379 26

A study of the enzymes of the glycogen pathway in Novikoff ascites hepatoma shows that glycogen synthetase has the lowest activity and that the tumour contains no high-K(m) soluble glucokinase. However, incubation of tumour cells with metabolizable sugars in vitro, or intraperitoneal administration of glucose into the tumour-bearing rat, results in glycogen accumulation by the tumour cells. Glycogen synthesis in the tumour is supported by aerobically produced ATP but is decreased anaerobically and by uncouplers of oxidative phosphorylation. Absence of P(i) from the incubation medium increases glycogen synthesis and decreases glycolysis. The optimum temperature for glycogen synthesis is 37 degrees . The capacity of the intact tumour cell to degrade deposited glycogen is low, but is accelerated by 2,4-dinitrophenol. Tumour homogenates prepared after osmotic shock do not incorporate [(14)C]glucose into glycogen. The glucose moiety of glucose 1-phosphate and of UDP-glucose is incorporated into glycogen by the homogenates and the incorporation of glucose 1-phosphate is greatly enhanced by AMP. Glucose 6-phosphate is a poor precursor of glycogen in the homogenate system, probably because it inhibits activation of phosphorylase b by AMP.
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PMID:Glycogen metabolism in Novikoff ascites-hepatoma cells. 429 92


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