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 have studied the reversibility of insulin receptor phosphorylation to establish the relation between this autophosphorylation reaction and the initiation of insulin action and between dephosphorylation and the termination of insulin effects in cells. In cultured Fao hepatoma cells labeled with 32PO4(3-), insulin increased 5-fold the phosphorylation of the beta-subunit of the insulin receptor at serine, threonine, and tyrosine residues. Addition of anti-insulin antiserum to cells incubated with insulin caused dissociation of insulin from the receptor and concurrent dephosphorylation of the beta-subunit. 32PO4(3-) associated with the insulin-stimulated receptor could be decreased by the addition of sodium phosphate to the medium but with a slower time course. Insulin stimulated phosphorylation of insulin receptor purified partially on immobilized wheat germ agglutinin. This reaction utilized [gamma-32P] ATP and occurred exclusively on tyrosine residues. Addition of unlabeled ATP caused a decrease in the amount of PO4(3-) associated with the receptor. Insulin-stimulated phosphorylation was also observed if the receptors were further purified by immunoprecipitation with anti-insulin receptor antibody prior to the phosphorylation reaction; however, addition of unlabeled ATP to this system did not chase the labeled 32PO4(3-) from the beta-subunit. These data are consistent with the notion that phosphorylation and dephosphorylation of the insulin receptor parallel the onset and termination of insulin action. Phosphatase activity involved in the dephosphorylation of the insulin receptor appears to be a glycoprotein because it was retained after partial purification of the receptor on wheat germ agglutinin-agarose; however, this phosphatase activity is distinct from the insulin receptor because it was not retained after immunoprecipitation of the receptor with anti-insulin receptor antibodies.
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PMID:Phosphorylation and dephosphorylation of the insulin receptor: evidence against an intrinsic phosphatase activity. 608 92

Immunofluorescent staining of HeLa cells with rabbit antiserum raised against isolated HeLa cell nucleoli showed bright nucleolar fluorescence. Immunoprecipitation of nuclear extracts obtained from HeLa cells labelled with 35S-methionine or 32P-orthophosphate followed by gel electrophoresis of the precipitate revealed a major band of 90 kd. This antigen, called pp90, was judged to be responsible for the nucleolar fluorescence. Serine residues were predominantly phosphorylated in pp90. Similar nucleolar fluorescence was observed commonly in human cells derived from malignant tumors including acute lymphatic leukemia, adult T-cell leukemia, hepatitis B virus-associated hepatoma, adenocarcinoma, and in 5 lymphoid cells derived from Burkitt lymphoma but not in normal human lymphocytes or liver cells. In immunoprecipitation, 32P-labelled pp90 was commonly detected as the major component in all of those cells which showed nucleolar fluorescence. Resting human embryo lung (HEL) cells were negative for both nucleolar fluorescence and pp90 in immunoprecipitation, but turned positive when stimulated to grow, suggesting the involvement of pp90 in cell growth. Antigen pp90 was also induced in human lymphocytes and HEL cells by infection with Epstein-Barr virus in human cytomegalovirus, respectively, which are known to induce cell DNA synthesis in early stages of infection. A cross-reacting nucleolar antigen was detected in 2 monkey cells but not in 3 rodent cells tested.
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PMID:A human nucleolar antigen (pp90) associated with cell growth and its induction by Epstein-Barr virus and human cytomegalovirus. 609 64

gamma-Glutamyl transpeptidase (gamma-GT) from human primary hepatoma was solubilised and purified 290-fold with 25% recovery. The kinetic and catalytic properties were compared with those purified from human fetal and normal adult liver. Hepatoma gamma-GT did not differ from the fetal and adult liver gamma-GT in its pH optima for transpeptidation and auto-transfer reaction, heat stability, Km for the two substrates and inhibition by L-serine + borate. Enzyme from the three sources behaved in a similar manner towards various cations, sulphhydryl reagents, amino acid dipeptides. Adult liver enzyme showed a 4 time higher Ki value for anthglutin than hepatoma and fetal liver. The hepatoma gamma-GT could not be differentiated from that of adult and fetal liver by concanavalin-A Sepharose 4B column chromatography. The tissue concentration of gamma-GT was 3 to 13 times higher in hepatoma and fetal liver than in adult liver.
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PMID:Isolation of gamma-glutamyl transpeptidase from human primary hepatoma and comparison of its kinetic and catalytic properties with the enzyme from normal adult and fetal liver. 611 39

We isolated the soluble forms of gamma-glutamyltransferase (EC 2.3.2.2; gamma-GT) from adult and fetal human liver and primary hepatoma and compared their properties. The Km value for L-gamma-glutamyl-p-nitroanilide and glycylglycine, the Ki for anthglutin, and the pH optimum were identical for the enzyme from all three sources. Nor were significant differences observed among the three in their heat stability, inhibition by serine and borate, or ability to transfer the gamma-glutamyl moiety to various amino acids and dipeptides. Unlike membrane-bound gamma-GT, the soluble form from all three sources entered polyacrylamide gel and showed identical electrophoretic mobilities. Treatment with neuraminidase decreased the electrophoretic mobilities to a similar extent. The relative molecular mass of the enzyme from each of the three sources is about 84 000. Immunoinhibition and immunoprecipitation of gamma-GT from the three sources by antibody to fetal liver gamma-GT followed an identical pattern. Gamma-GT from fetal liver and hepatoma differed significantly from that of adult liver in affinity for wheat-germ agglutinin and Ricinus communis agglutinin (RCA-120). In many of the properties studied, soluble gamma-GT resembles the papain-digested form of membrane-bound gamma-GT.
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PMID:Soluble forms of gamma-glutamyltransferase in human adult liver, fetal liver, and primary hepatoma compared. 612 78

Murine extra-embryonic endodermal cell lines derived from either teratocarcinomas or mouse embryos contain a cytoskeletal protein (Endo A) of Mr = 55,000. Endo A was immunoprecipitated from [35S]methionine-labeled lysates of three parietal endodermal cell lines, A presumptive visceral endodermal cell line, and a fetal hepatoma cell line, but not from fibroblasts, myoblasts, erythroleukemic cells, neuroblastoma cells, keratinocytes, or embryonal carcinoma cells. Embryonal carcinoma cells induced to differentiate by exposure to retinoic acid synthesized increased amounts of Endo A approximately 48 h after exposure to the inducer. Two-dimensional gel analysis of immunoprecipitated samples confirmed that Endo A is distinct from vimentin and murine keratinocyte proteins recognized by two different keratin antisera. Comparison by two-dimensional gel electrophoresis of immunoprecipitated Endo A labeled with either [35S]methionine or [32P]orthophosphate indicated that the multiple forms of Endo A resolved by isoelectric focusing were due, at least in part, to phosphorylation. Serine was identified as the phosphorylated amino acid. Endo A was the only major antigenic protein found in a parietal endodermal cell line which was recognized by a monoclonal antibody prepared by other investigators against trophoblast cytoskeletons. The results indicate that Endo A, like the previously described Endo B protein, is distinct from other cytoskeletal proteins and will be useful as a marker of the differentiation of murine embryonal carcinoma cells to extra-embryonic endoderm.
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PMID:Developmental expression of murine extra-embryonic endodermal cytoskeletal proteins. 617 20

Experimental hepatoma of the rats was induced by chronic administration of 3'-methyl-dimethylamino-azobenzene. The folate level of the hepatoma-bearing rats tended to be low as compared with that of normal controls, and the co-existence of folate deficiency and reduced motor nerve conduction velocity of the dorsal nerve trunks appeared not uncommon. The hepatoma-bearing rats revealed the disturbance of serine to glycine conversion in serum, and folate administration to them prevented electrophysiological neuropathy along with normalization of serine to glycine conversion. Therefore, the reduced motor nerve conduction velocity could be at least in part the result of a metabolic impairment due to folate deficiency.
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PMID:The role of folate deficiency in electrophysiological neuropathy of experimental hepatoma of the rats. 629 3

Plasminogen activators are membrane-associated, arginine-specific serine proteases which convert the inactive plasma zymogen plasminogen to plasmin, an active, broad-spectrum serine protease. Plasmin, the major fibrinolytic enzyme in blood, also participates in a number of physiologic functions involving protein processing and tissue remodelling, and may play an important role in tumor invasion and metastasis. In HTC rat hepatoma cells in tissue culture, glucocorticoids rapidly decrease plasminogen activator (PA) activity. We have shown that this decrease is mediated by induction of a soluble inhibitor of PA activity rather than modulation of the amount of PA. The hormonally-induced inhibitor is a cellular product which specifically inhibits PA but not plasmin. We have isolated variant lines of HTC cells which are selectively resistant to the glucocorticoid inhibition of PA but retain other glucocorticoid responses. These variants lack the hormonally-induced inhibitor; PA from these variants is fully sensitive to inhibition by inhibitor from steroid-treated wild-type cells. Cyclic nucleotides dramatically stimulate PA activity in HTC cells in a time- and concentration-dependent manner. Paradoxically, glucocorticoids further enhance this stimulation. Thus glucocorticoids exert two separate and opposite effects on PA activity. The availability of glucocorticoid-resistant variant cell lines, together with the unique regulatory interactions of steroids and cyclic nucleotides, make HTC cells a useful experimental system in which to study the multihormonal regulation of plasminogen activator.
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PMID:Hormonal regulation of plasminogen activator in rat hepatoma cells. 631 82

Ochratoxin A (OTA), a naturally occurring mycotoxin of Aspergillus and Penicillium species, consists of a 5' chlorinated dihydromethyl isocoumarin linked to L,beta-phenylalanine by an alpha-amide bond. 8 analogues of OTA were prepared in which the phenylalanine was always substituted by another amino acid. The effects of these analogues on yeast tRNA amino acylation reaction and on growth and protein synthesis of hepatoma culture cells were compared with those of OTA. In addition, Ochratoxin B (OTB) and ochratoxin alpha (OT alpha) were examined. All the analogues of OTA had inhibitory effects in the 3 test systems, although to a lesser degree than OTA. The degree of inhibition depended on the kind of substituted amino acid, the tyrosine, valine, serine and alanine analogues being most effective, in contrast to the proline analogue. OTB and OT alpha were ineffective.
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PMID:Comparative study of the effect of ochratoxin A analogues on yeast aminoacyl-tRNA synthetases and on the growth and protein synthesis of hepatoma cells. 636 78

The effect of the tumor-promoting agent phorbol 12-myristate 13-acetate (PMA) on insulin receptors and insulin action was studied in rat hepatoma cells in culture. PMA (0.1-1.0 micrograms/ml) did not affect insulin binding either acutely or chronically but inhibited insulin stimulation of glycogen synthase and tyrosine aminotransferase. PMA (1 microgram/ml) stimulated the phosphorylation of the beta subunit of insulin receptor purified from [32P]phosphate-labeled Fao cells by 1.3-fold in the absence of insulin. In contrast, insulin-stimulated phosphorylation in the presence of PMA was reduced. Phosphoamino acid analysis of the beta subunit after PMA stimulation revealed an increase of both phosphoserine and phosphothreonine residues, whereas insulin stimulated primarily phosphorylation of tyrosine and serine residues. Insulin stimulation of cells after PMA treatment revealed a decrease in phosphotyrosine when compared to cells stimulated by insulin alone. Tryptic peptide mapping of the beta subunit by a two-dimensional chromatographic/electrophoretic separation revealed nine phosphopeptides from the cells treated with PMA. Insulin stimulated phosphorylation at six new sites in the receptor, three of which appeared to be similar to those in PMA-treated cells. This report shows that phorbol esters stimulate insulin receptor phosphorylation, inhibit insulin-induced receptor phosphorylation and insulin action, and suggest a physiologic relation between insulin action and the calcium-activated and phospholipid-dependent protein kinase C.
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PMID:Phorbol esters modulate insulin receptor phosphorylation and insulin action in cultured hepatoma cells. 639 28

Serine palmitoyltransferase (EC 2.3.1.50) catalyzes an initial and regulatory reaction of sphingolipid biosynthesis, the formation of a homologue of 3-ketosphinganine from L-serine and a fatty acyl coenzyme A thioester. We have demonstrated that this enzyme exists in microsomes from Morris hepatoma 7777 and, moreover, found that its specific activity was 199 +/- 23 pmol/min/mg of microsomal protein, which was significantly higher than that for microsomes from host (69 +/- 4.2 pmol/min/mg; S.D.) or control (43 +/- 4.1 pmol/min/mg) rat livers when assayed under optimal conditions. The activities varied with tumor weight. For comparison, the activities of microsomes from regenerating liver were also higher; whereas fetal and neonatal rat livers had substantially lower activities. Assays conducted without added pyridoxal 5'-phosphate revealed that the enzyme in microsomes isolated from the tumor was more readily depleted of this cofactor than was that in control microsomes; this phenomenon was most pronounced with the larger tumors. The other properties of the enzyme resembled those for liver. On the basis of these experiments, we propose that the elevated proportions of sphingomyelin and other sphingolipids found in hepatomas and regenerating rat liver are related to increases in long-chain base synthesis by serine palmitoyltransferase. Since the activity is apparently more sensitive to the availability of pyridoxal 5'-phosphate in the hepatoma, this reaction could become limiting under more severe vitamin B6 deficiencies.
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PMID:Comparison of serine palmitoyltransferase in Morris hepatoma 7777 and rat liver. 671 93


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