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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 activity was measured in plasma membranes isolated form Morris Hepatomas (44 and 47C) and from their host livers. We found that the enzyme activity in the tumours was very low, approx. 5% of the level in control and host livers. The amount of cAMP and cGMP in the tumours was also lower than in the host livers but the ratio of cGMP to cAMP in the tumours was increased by a factor of 4-5. The membrane binding capacities for the pancreatic hormones insulin and glucagon were measured. Hepatoma membranes bound less glucagon than those of livers. A decrease in the number of the glucagon receptors was found but there were no changes in the affinity constant. For insulin, we found the same binding capacity as the host and control livers; thus there was an increase in the ratio of insulin bound/glucagon bound in tumours as compared to controls. The plasma levels of insulin in the tumour bearing animals were approximately half of those in control, whereas the glucagon levels in plasma were 60-62% higher in tumour bearing animals. These results are discussed in terms of the characterization of normal, foetal and regenerating liver, in comparison with slow growing hepatomas. The levels of cAMP and cGMP are discussed with respect to control mechanisms of cell proliferation.
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PMID:Some enzyme and hormonal attributes of hepatoma cell membranes. 625 69

Urinary excretion of cyclic GMP (cGMP) and the plasma level of cyclic AMP (cAMP) were determined in patients with liver diseases. The urinary excretion of cGMP, expressed on the basis of creatinine excreted per day, was at significantly higher levels not only in primary hepatoma but also in liver cirrhosis, while the plasma level of cAMP was higher only in liver cirrhosis. Thus, the ratio of urinary cGMP excretion to plasma cAMP level in primary hepatoma was significantly higher than that in liver cirrhosis. In cirrhotic patients studied by catheterization, the level of cGMP in the hepatic vein was significantly lower than that in the superior mesenteric or portal vein, indicating the uptake of cGMP by the liver. Since cGMP excretion correlated with KICG both in liver cirrhosis and primary hepatoma, the increased cGMP excretion appeared to be explained by a reduced uptake of cGMP by the liver.
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PMID:Increased excretion of urinary cyclic GMP in primary hepatoma and preneoplastic liver. 629 71

A cyclic nucleotide-independent, polyamine-responsive protein kinase from the cytosol of Morris hepatoma 3924A, which phosphorylated heat-stable endogenous substrates and casein in the presence of polyamines (Criss, W.E., Yamamoto, M., Takai, Y., Nishizuka, Y. and Morris, H.P. (1978) Cancer Res. 38, 3540-3545) was observed to be stimulated by an endogenous protein activator. This protein activator was identified to be calmodulin. the polyamine-responsive protein kinase was also stimulated by purified calmodulin, but only in the presence of polyamines such as polylysine. This action of calmodulin did not require Ca2+ for activation of the enzyme; and activation occurred in the presence of EGTA. DNA and RNA inhibited the polyamine-responsive protein kinase, either in the presence or absence of Ca2+. Purified calmodulin, in the presence of cyclic AMP or cyclic GMP, did not activate the protein kinase. Therefore, polyamines such as polylysine are an absolute requirement for this expression of calmodulin action. The increased enzyme activity by calmodulin was accompanied with an increased Vmax and with no changes in the Km (ATP). High levels of cation, up to 100 mM Mg2+, did not effect the action of calmodulin. These results indicate that tumor cytosolic polyamine-responsive protein kinase is regulated by calmodulin, the latter being increased in the tumor tissue.
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PMID:Calmodulin stimulates polyamine-responsive protein kinase in the absence of Ca2+. 629 10

We have separated and characterized a Ca2+- and calmodulin-insensitive cyclic nucleotide phosphodiesterase from rat liver supernatant as well as an analogous enzyme from HTC hepatoma cells. Chromatography of rat liver supernatant on DEAE-cellulose in the presence and subsequently in the absence of 0.1 mM-CaCl2 resulted in the separation of two distinct phosphodiesterase activities, both of which preferentially hydrolysed cyclic GMP rather than cyclic AMP. One enzyme, E-Ib, was activated in the presence of Ca2+ and calmodulin, and the other, E-Ia, was not. The E-Ia enzyme, which did not bind to calmodulin-Sepharose, had Mr 325 000 and displayed anomalous kinetic behaviour [Km (cyclic GMP) 1.2 microM; Km (cyclic AMP) 15.4 microM]. The E-Ib enzyme, which bound to calmodulin-Sepharose in the presence of Ca2+, had Mr 150 000 and exhibited Michaelis-Menten kinetics for hydrolysis of cyclic GMP [Km (basal) 6.5 microM; Km (activated) 12.0 microM]. E-Ia activity was diminished by incubation with alpha-chymotrypsin and was unaffected by the action of a rat kidney lysosomal proteinase. Partial hydrolysis of E-Ib enzyme by alpha-chymotrypsin or the kidney proteinase resulted in irreversible activation of the enzyme. The E-I enzyme isolated from HTC hepatoma cells was similar to the rat liver E-Ia enzyme in many respects. Its apparent Mr was 325 000. Its activity was unaffected by calmodulin in the presence of Ca2+ or by incubation with the kidney proteinase, and was decreased by digestion with alpha-chymotrypsin. Unlike the liver E-Ia enzyme, however, the hepatoma enzyme exhibited normal kinetic behaviour, with Km (cyclic GMP) 3.2 microM. Although HTC cells contain two other phosphodiesterases analogous to those in rat liver and a calmodulin-like activator of phosphodiesterase, no calmodulin-sensitive phosphodiesterase was detected.
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PMID:Ca2+-independent cyclic GMP phosphodiesterases from rat liver and HTC hepatoma cells. 631 Nov 63

Four main phosphodiesterase (PDE) forms were resolved and partially purified from rat liver and Morris hepatoma 5123tc(h). The activities of the high Km cyclic nucleotide PDE (form II) in hepatoma were markedly reduced compared to liver, while the activities of the low Km cAMP PDE (form III) and low Km cyclic nucleotide PDE (form IV) in hepatoma were markedly higher than those of liver. The partially purified low Km cAMP PDE's (forms III and IV) from liver showed non-linear Lineweaver-Burk plots, whereas the same enzyme forms in hepatoma displayed linear kinetics. Activation of low Km cGMP PDE activity by calmodulin was found with form I in liver whereas in hepatoma form II was responsive to calmodulin.
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PMID:The isolation and characterization of cyclic nucleotide phosphodiesterases from Morris hepatoma 5123tc(h) and rat liver. 632 Dec 59

Adenylate cyclase activity was measured in plasma membranes isolated from Morris Hepatoma 7800 and from control and host livers. The only difference found in tumor enzyme activity was the lack of response to glucagon. The membrane-binding capacities for the pancreatic hormones insulin and glucagon were measured. Hepatoma membranes did not bind glucagon. Insulin-binding parameters could not be determined because of high non-specific binding. The plasma levels of insulin in the tumor-bearing animals were approximately half of those found in controls, whereas the glucagon levels in plasma were 50% higher in tumor-bearing animals. Thyroxine and triiodothyronine plasma levels were reduced in tumor-bearing rats, while the thyroid-stimulating hormone level was within normal limits. The amount of cAMP (275 pmol g-1) and cGMP (3.6 pmol g-1) in the tumor were lower than in the host and control livers, but the ratio of cGMP to cAMP in the tumor was increased by a factor of 2. These results are discussed with respect to control mechanisms of cell proliferation in comparison with other hepato-proliferative states.
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PMID:Hormonal changes and adenylate cyclase system in rat bearing 7800 Morris hepatoma. 634 40

The phosphorylation of endogenous membrane proteins by an endogenous protein kinase was studied in isolated plasma membranes from AH-66 hepatoma ascites cells using [gamma-32P]ATP as a precursor. The phosphorylation occurred very rapidly in the presence of 10 mM Mg2+ and reached a maximal level at 2 min. Ca2+ strongly inhibited the phosphorylation reaction and antagonized the activation produced by Mg2+. Neither cyclic AMP nor cyclic GMP had a significant effect on the phosphorylation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography showed that only membrane proteins ranging in molecular weight from 125,000 to 200,000 were heavily phosphorylated and those of less than 60,000 molecular weight were not phosphorylated at all. The protein kinase activity was readily extractable from the plasma membranes with 1 mM EDTA at pH 8.5. Among exogenous substrates, the extracted protein kinase catalyzed the phosphorylation of histone, protamine and phosvitin rather than casein. When the extracted protein kinase was subjected to chromatography on DEAE-Sepharose, a single major peak of cyclic AMP-independent protein kinase was eluted at a position quite different from those of the cytosolic protein kinases.
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PMID:Endogenous protein phosphorylation in isolated plasma membranes of AH-66 hepatoma ascites cells. 728 78

The hepatic receptor for asialoglycoproteins was found to be modulated by the glucose concentration in the medium of the human hepatoma cell line HepG2. The surface binding of asialoorosomucoid, a well-documented ligand for this receptor, increased from 20 ng/mg of cellular protein to about 40 ng/mg as the glucose concentration was increased from 10 to 50 mg/dl. The up-modulating effect of glucose was mimicked by pyruvate, a product of glucose metabolism, and abolished by both 2-deoxyglucose, an inhibitor of glucose metabolism, and by cycloheximide, an inhibitor of protein synthesis. Scatchard plot analysis indicated a rise in the number of binding sites and a twofold increase in binding affinity. In contrast, the binding of antibody remained unchanged with respect to alterations in glucose concentration, an indication that the actual number of receptors remained constant in face of an increased number of binding sites. Specificity of the glucose effect was shown by the binding of insulin and transferrin to their respective receptors, which was unaffected by the high glucose concentration that increased asialoorosomucoid binding. The repression of receptor binding seen with cells grown in biotin-deprived medium was reversed by increasing the glucose concentration of the medium. In this case, binding was restored to a level sixfold to sevenfold higher than that of the control cells grown in dialyzed serum. The stimulatory effect of glucose was shown to be independent of and significantly greater than that of cyclic GMP, a known regulator of receptor expression of biotin-deficient HepG2 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of the asialoglycoprotein receptor in human hepatoma cells: effect of glucose. 829

1. This study was designed to determine the role of sodium-potassium adenosine triphosphatase (Na(+)-K(+)-ATPase) in the regulation of human corpus cavernosum smooth muscle contractility by nitric oxide (NO). In addition, we determined if the modulation of Na(+)-K(+)-ATPase activity by NO is dependent on the increase in intracellular cyclic GMP concentration. 2. The effect of NO donors, sodium-nitroprusside (SNP) and S-nitroso-glutathione (S-NO-Glu), and a permeable cyclic GMP analogue, 8-bromo-cyclic GMP, on Na(+)-K(+)-ATPase activity (measured as ouabain-sensitive 86Rb-uptake) was studied in human cultured corpus cavernosum smooth muscle cells (HCCSMC). In addition, the effect of the cyclic GMP lowering agent, methylene blue, on NO-induced increase in Na(+)-K(+)-ATPase activity was studied. 3. SNP (1 microM) caused time-dependent increases in ouabain-sensitive Rb-uptake (33-72%) over 2-20 min in HCCSMC. The stimulation of ouabain-sensitive Rb-uptake by SNP was concentration-dependent (30 and 102% with 0.1 and 1 microM SNP, respectively). Similarly, significant increases in ouabain-sensitive Rb-uptake were obtained with 1 and 10 microM S-NO-Glu. In contrast, incubation of HCCSMC with 8-bromo-cyclic GMP (100 microM) did not increase ouabain-sensitive Rb-uptake. 4. S-NO-Glu induced-increase in intracellular cyclic GMP synthesis, but not the increase in ouabain-sensitive Rb-uptake, was completely inhibited by methylene blue in HCCSMC. 5. The Na(+)-K(+)-ATPase inhibitor, ouabain, caused a concentration-dependent increase in tension (0.5 to 2 fold) in tissues contracted with 15 mM KCl. SNP and S-NO-Glu caused a concentration-dependent relaxation (concentration required to cause half maximal relaxation (ED50) = 0.04 and 0.2 microM, respectively) of HCC strips contracted with 15 mM K+. Ouabain (0.1 to 10 microM) inhibited the response to SNP and S-NO-Glu by shifting the concentration-response curves to the right and preventing full smooth muscle relaxation.6. These results indicate that the activity of Na+-K+-ATPase modulates the contractility of HCC smooth muscle, and that NO stimulates Na+-K+-ATPase activity in HCCSMC independently of its ability to increase the intracellular cyclic GMP concentration. They also suggest that stimulation of Na+-K+-ATPase activity plays an important role in NO-induced relaxation of HCC smooth muscle
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PMID:Possible role of Na(+)-K(+)-ATPase in the regulation of human corpus cavernosum smooth muscle contractility by nitric oxide. 856 49

PDE3 or cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI PDE) activity was detected in homogenates of HepG2, Hep3B and HuH7, but not SK-Hep-1, human hepatoma cells. In HepG2 and Hep3B cells PDE3 activity was found predominantly in particulate fractions; in HuH7, in both particulate and supernatant fractions. cDNAs encoding two human PDE3s (an 'adipocyte' type, HcGIP1, and a 'cardiovascular' type, HcGIP2) have been cloned. HcGIP1 cDNA hybridized strongly with poly(A)+ RNA species from HepG2 and Hep3B. Both HcGIP1 and HcGIP2 mRNAs were expressed in Hep3B and HuH7 cells. The nucleotide sequence of an approximately 300-bp cDNA fragment, isolated after RT-PCR cloning from HepG2 RNA, was identical to a sequence within the conserved domain of HcGIP1 cDNA, consistent with the presence of HcGIP1 mRNA in HepG2 cells.
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PMID:Differential expression of cGMP-inhibited cyclic nucleotide phosphodiesterases in human hepatoma cell lines. 870 23


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