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)

Adenylate cyclase can be resolved into at least two proteins, a thermolabile, N-ethylmaleimide-sensitive component and a second protein (or proteins) that is more stable to either of these treatments. Neither component by itself catalyzes the formation of cyclic AMP using MgATP as substrate. However, mixture of the two reconstitutes MgATP-dependent fluoride- and guanyl-5'-yl imidodiphosphate (Gpp(NH)p)-stimulatable adenylate cyclase activity. The more stable component can be resolved from the first in various tissues or cultured cells by treatment of membrnes or detergent extracts with heat or N-ethylmaleimide. The two proteins have also been resolved genetically in two clonal cell lines that are deficient in adenylate cyclase activity. An adenylate cyclase-deficient variant of the S49 lymphoma cell (AC-) contains only the thermolabile activity, while the activity of the more stable protein is found in a complementary hepatoma cell line (HC-1). In addition, AC-S49 cell plasma membranes contain MnATP-dependent adenylate cyclase activity. The protein that catalyzes this reaction appears to be the same as that which can combine with the thermostable component to reconstitute Mg2+-dependent enzyme activity because both activities co-fractionate by gel exclusion chromatography and sucrose density gradient centrifugation, both activities have identical denaturation kinetics at 30 degrees C, and both activities are stabilized at 30 degrees C and labilized at 0 degree C by various nucleotides and divalent cations with similar specificity. It is thus hypothesized that the thermolabile factor is the catalytic subunit of the physiological adenylate cyclase and that the Mn2+-dependent activity is a nonphysiological expression of the catalytic protein. The thermostable moiety of the enzyme, which is proposed to serve a regulatory function, appears to consist of two functional components, based upon differential thermal lability of its ability to reconstitute hormone-, NaF-, or Gpp(NH)p-stimulated adenylate cyclase activity. These components have not, however, been physically separated. The thermolabile and thermostable components can interact in detergent solution or in a suitable membrane. Mixing of the detergent-solubilized regulatory component with AC-membranes that contain only the catalytic protein and beta-adrenergic receptors reconstitutes catecholamine-stimulatable adenylate cyclase activity; however, addition of the catalytic protein to membranes that contain receptor and the regulatory component yields MgATP-dependent enzymatic activity that is unresponsive to hormone.
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PMID:Reconstitution of hormone-sensitive adenylate cyclase activity with resolved components of the enzyme. 21 Jan 83

Post-ribosomal supernatant extracts from Yoshida AH 130 ascites hepatoma cells promote the in vitro association of ribosomal subunits at low Mg2+ concentration. Comparable extracts from rat liver show, on the contrary, dissociation factor activity on ribosome monomers.
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PMID:Reassociation of eukaryotic ribosomal subunits by a factor from rat ascites hepatoma cytosol. 49 6

The effects of increasing extracellular concentrations of Ca2+ and Mg2+ on the uptake of 14C-thymidine, 3H-uridine and 14C-leucine by Novikoff hepatoma and normal liver cells have been studied. Increasing concentrations of Ca2+ stimulate all the three incorporations while Mg2+ exhibits an inhibitory effect. Liver cells presented a higher cation permeation induced by the extracellular concentration than hepatoma cells which also seems to explain the quantitative differences observed in the studied syntheses. The importance of the extracellular cation-cell membrane interaction in these effects is discussed.
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PMID:Effects of extracellular Ca2+ and Mg2+ on nucleic acids and proteins syntheses by tumor and normal liver cells. 70 Sep 6

Deoxyribonucleic acid polymerase-beta (EC 2.7.7.7) has been purified over 100 000-fold from a whole cell extract of guinea pig liver. The enzyme yields a single stainable band when subjected to non-denaturing polyacrylamide gel electrophoresis, and this band corresponds to the DNA polymerase activity when a sister gel is sliced and assayed. The final fraction has a specific activity of 21 000 units/mg; this value can be increased significantly by addition of various components, including glycols, polyamines or any of several protein factors which can be purified from the crude extract. The DNA polymerase-beta lacks detectable exonuclease or endonuclease activity, has an alkaline pH optimum and has a requirement for all four deoxyribonucleoside triphosphates, a divalent cation and a primer-template for maximal activity. While activated DNA is the preferred primer-template, the enzyme is capable of utilizing native and denatured DNA as well as several synthetic polynucleotides as primer-templates. The latter are especially effective when manganese is the divalent cation. Magnesium, at 10 mM, is the preferred divalent cation when activated DNA is used. Manganese, and to a lesser extent cobalt, can substitute for magnesium while zinc and calcium cannot. The beta-polymerase has a half-life of 10 min at 40 degrees C and this is increased in the presence of either DNA or NaCl. The enzyme is stimulated by glycols, polyamines and NaCal or KCl, and is inhibited by several known inhibitors of DNA polymerase activity including o-phenanthroline, heparin, organic solvents and sulfhydryl blocking agents. Guinea pig liver DNA polymerase-beta is remarkably similar to the rat Novikoff hepatoma beta-polymerase with respect to its isoelectric point of 8.4 and its molecular weight of 32 000 as determined by sucrose gradient centrifugation under high or low salt conditions or sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This similarity is further extended to the removal, at the final step in purification, of a protein capable of stimulating the homogeneous enzyme. Removal of this protein could explain the lower molecular weight of the guinea pig and other rodent-derived beta-polymerases, when compared to the beta-polymerases from other systems.
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PMID:Purification and properties of DNA polymerase-beta from guinea pig liver. 70 39

DNase activity in the presence of Ca2+ + Mg2+, Mg2+ alone, Mn2+ alone, or EDTA, and topoisomerase I activity were measured in nuclear extracts of diethylnitrosamine (DEN)-induced hepatomas, regenerating, fetal, and normal rat livers. In hepatoma tissue, the Ca/Mg-dependent DNase activity was lower than in normal tissue and nearly the same as in fetal liver. In the poorly differentiated hepatomas, Mn-dependent DNase activity was higher than in both moderately and well differentiated ones and than in normal liver tissue. The activity of topoisomerase I in hepatomas and in regenerating liver was lower than in normal liver tissue.
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PMID:Nuclear topoisomerase I and DNase activities in rat diethylnitrosamine-induced hepatoma, in regenerating and fetal liver. 166 44

Plasma membrane fractions from normal, regenerating liver and the AS-30D ascites hepatocarcinoma exhibited a high degree of enrichment when a set of plasma membrane enzyme markers were studied in comparison to the ones associated to the mitochondrial and cytosolic compartments. While the (Ca2+, Mg2+)-ATPase observed for the plasma membrane fraction isolated from normal liver showed an activity of 1.2 mumoles/mg/min, the regenerating liver and the AS-30D plasma membrane fractions presented a much lower ATPase activity (0.3 and 0.22 mumoles/mg/min respectively). Despite the differences in ATPase activity observed between models, the plasma membrane fraction from the AS-30D hepatocarcinoma presented a calcium transport activity similar to the value observed for the normal system (5.9 and 5.5 nmoles Ca2+/mg/10 min, respectively). Interestingly, the ATP in equilibrium with Pi exchange experiments carried out with the different plasma membrane fractions revealed that the (Ca2+, Mg2+)-ATPase contained in the plasma membrane from the AS-30D cells shows an exchange activity of 26 nmoles ATP in equilibrium with Pi/mg/min, similar to the one observed fo the enzyme from normal liver (30 nmoles ATP in equilibrium with Pi/mg/min). Our results suggest that the plasma membrane from the transformed model presents a more efficient mechanism to regulate the movement of calcium through the calcium pump, with an optimum expenditure of energy.
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PMID:Altered coupling states between calcium transport and (Ca2+, Mg2+)-ATPase in the AS-30D ascites hepatocarcinoma plasma membrane. 182 60

To determine whether abnormal metabolism of L-fucose in hepatocellular carcinoma is accompanied by alterations in the activities of fucosyltransferases, the latter were determined in plasma and liver tissue of patients with this disease and in cirrhotic and normal subjects. Activities of alpha-2/alpha-3 and alpha-6-L-fucosyltransferases were all significantly greater in plasma from patients with hepatocellular carcinoma than in plasma from cirrhotic patients or normal subjects (p less than 0.025). The activity of each enzyme was dependent, to a similar extent, on Mn2+, Mg2+ and triton X-10, irrespective of the source, and all displayed pH optimums in the range of 7.5 to 8.0. In contrast, activities of alpha-2/alpha-3 fucosyltransferases were significantly lower (p less than 0.025) in homogenates prepared from tumorous liver tissue than in that prepared from nontumorous tissue from hepatocellular carcinoma and cirrhotic patients, whereas for the alpha-6 enzyme the situation was reversed (typically, tumor tissue levels were 5 pmol/hr/mg; in nontumor tissue they were 2 pmol/hr/mg). Activities of galactosyl and mannosyltransferase in tumor tissue were greater in all cases than in nontumor cirrhotic tissue. Plasma fucosyltransferases are specifically elevated in hepatocellular carcinoma but different mechanisms appear to underlie the changes seen for alpha-2/alpha-3 and alpha-6-L-fucosyltransferases.
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PMID:Fucosyltransferases: differential plasma and tissue alterations in hepatocellular carcinoma and cirrhosis. 184 14

A plasma membrane-rich fraction has been separated from liver cells and cells of two solid rat tumors. D23 hepatoma and MC7 sarcoma. On the basis of marker enzyme activity the membranes separating at the 31-41% interface on the discontinuous sucrose gradient were enriched 15- to 19-fold. No significant differences in the phospholipid (PL) composition of the three membrane fractions were observed. The PL fatty acid (FA) composition showed that the percentage of unsaturated FA in all three membranes was between 43 and 48%. However, the oleic acid:PUFA ratio was much greater from tumor membranes. Membrane cholesterol was also significantly lower for cells from both tumors compared with liver cells. The DPH fluorescence polarization of the membrane fractions showed that the membranes from cells of both tumors are significantly less ordered than those of liver at all temperatures measured (4-50 degrees C). The Mg2+ ATPase activity of the plasma membranes is inactivated by hyperthermia treatments. The enzyme from liver cells was more thermostable (LT50 = 53.86 degrees C) than that from cells of either D23 (LT50 = 47.51 degrees C) or MC7 (LT50 = 46.34 degrees C) tumors.
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PMID:Lipid composition of the membranes from cells of two rat tumors and its relationship to tumor thermosensitivity. 198

Highly purified GH-receptor preparations from 3T3-F442A fibroblasts, whose differentiation into adipocytes is promoted by GH, have been shown to contain a tyrosine kinase capable of phosphorylating GH receptors. In the current work, characteristics of the tyrosine kinase responsible for the in vitro phosphorylation of GH receptors from cultured 3T3-F442A fibroblasts were examined, and the presence of this GH receptor-associated tyrosine kinase activity was demonstrated in multiple cell types. GH-receptor complexes from GH-treated cells were partially purified by immunoprecipitation using anti-GH antibodies and then incubated as an immune complex with [gamma 32P] ATP. Incorporation of 32P into the GH receptor from 3T3-F442A fibroblasts was apparent within 1 min at 30 C after the addition of [gamma 32P]ATP (5-10 microM). A divalent cation was requisite for the phosphorylation; Mn2+ was significantly more effective than Mg2+ and Co2+; Ba2+, Ca2+, or Zn2+ had no effect. Excess unlabeled ATP, but not cytosine triphosphate, GTP, or uridine triphosphate, abolished 32P incorporation into the GH receptor and [gamma 32P]GTP could not replace [gamma 32P]ATP as a source of 32P. At 5.5 mM Mn2+, phosphorylation exhibited a biphasic dose response to ATP, with maximal phosphorylation occurring at a concentration of 10 microM ATP. At more physiological concentrations of ATP (1 mM), phosphorylation of the GH receptor was also stimulated by lower concentrations of Mn2+ (as low as 500 nM). Optimal reaction conditions determined for the phosphorylation reaction in 3T3-F442A fibroblasts were used to demonstrate incorporation of 32P from [gamma 32P]ATP into partially purified GH receptors from cultured human IM-9 lymphocytes, murine 3T3-F442A adipocytes, rat H-35 hepatoma cells, and freshly isolated rat adipocytes. The 32P was shown to be incorporated into tyrosyl residues in receptors from the two cell types tested (IM-9 lymphocytes and rat adipocytes). Cross-linked [125I] hGH-receptor complexes solubilized from the four cell types (IM-9 lymphocytes, 3T3-F442A adipocytes, H-35 hepatoma cells, and freshly isolated rat adipocytes) bound to and could be eluted from phosphotyrosyl antibody, suggesting that tyrosyl phosphorylation of GH receptors in all of these cells occurs in vivo. The presence of tyrosine kinase activity associated with GH receptors in multiple cell types from different species is consistent with tyrosine kinase activity playing a role in the actions of GH.
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PMID:Demonstration of growth hormone (GH) receptor-associated tyrosine kinase activity in multiple GH-responsive cell types. 217 17

The DNA endonuclease (Aendo) and DNA topoisomerase (Atopo) activities in liver nucleus extracts of normal rats, in DENA-induced hepatomas and in liver tissues around tumours were investigated. The profile of nuclear endonucleases measured in the presence of 2 mM CaCl2 + 5 mM MgCl2, or 5 mM MnCl2, or 5 mM MgCl2, or 2 mM CaCl2 (pH 7.4), or I mM EDTA (pH 5.0) was different in normal and tumour tissues. Mn2+-dependent endonuclease was the main endonuclease in the tumour tissue, whereas Ca2+, Mg2+-dependent endonuclease was the main one in the normal liver and in the tissue around the tumour. An increase in the Mn2+-dependent endonuclease activity correlated with a decrease in the hepatoma differentiation level. Atopo of types I and II increased in the tissue around the tumour. Aendo and Atopo of cellular nuclei decreased in animals given DENA without the liver tumour.
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PMID:[The activity of nuclear endonucleases and topoisomerases in the liver of rats and in diethylnitrosamine-induced tumors]. 254 92


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