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)

Total superoxide dismutase (SOD) and manganese superoxide dismutase (Mn SOD) specific activities were measured in tissue homogenates and in isolated mitochondria from normal rat liver and three Morris hepatomas of different growth rates. Total SOD and Mn SOD specific activities were decreased in all tumor homogenates when compared to normal liver; the lowest activity was associated with the fastest growing tumor. These results are consistent with the hypothesis that total Mn SOD specific activity is decreased in all tumors. The Mn SOD specific activity was similar to the total SOD specific activity of isolated mitochondria, indicating that mitochondrial SOD is almost entirely manganese containing. This activity was decreased in the fast- and medium-growth-rate hepatomas but was slightly increased in the tumor with the slowest growth rate when compared to liver. The normal or higher than normal mitochondrial Mn SOD specific activity indicates that decreased mitochondrial SOD specific activity is not a characteristic of all tumors. Superoxide radical (O2-.) formation was measured in submitochondrial particles obtained by sonication of isolated mitochondria and subsequent washings to remove the SOD. The difficulty encountered in reducing the SOD activity suggests that at least part of the mitochondrial SOD might be associated with the mitochondrial membrane. In liver submitochondrial particles, O2-. was formed only when succinate and antimycin A were used together, as substrate and inhibitor of the electron transport chain, respectively. In the hepatomas studied for O2-. production (slow- and fast-growth rates), the formation of the radical was detected in the presence of succinate even when no inhibitor was present. Antimycin A stimulated the production of O2-. in normal rat liver and slow-growth-rate tumor, but not in fast-growth-rate tumor submitochondrial particles. Reduced nicotinamide adenine dinucleotide did not lead to the production of O2-. by normal liver or hepatoma submitochondrial particles. Mitochondrial membrane damage was seen in micrographs of the medium- and fast-growing hepatomas. This could be a consequence of low mitochondrial SOD concomitant with a flux of superoxide, if the radical is produced in vivo by these mitochondria.
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PMID:Superoxide dismutase and superoxide radical in Morris hepatomas. 625 38

1. The activities of cyclic cytidine 3',5'-monophosphate (cCMP) phosphodiesterase in normal rat liver and host liver (bearing hepatoma 5123 t.c.(h)) were compared with those of three Morris hepatomas of varying growth rates. 2. The results show that the order of enzyme activity was as follows: normal liver = host liver greater than 7794A (slow growth rate) greater than 5123 t.c.(h) (intermediate growth rate) greater than 7800 (fast growth rate). 3. The enzyme had a pH optimal value of about 7.0 and an apparent Km for cCMP about 2.8 mM; its activity was slightly affected by the presence of calmodulin (100 micrograms/ml) and/or CaCl2 (100 microM), but showed variable responses to other cations (La3+, Mg2+, Mn2+, Zn2+, Fe2+, Na+ and K+).
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PMID:Decreased activities of cyclic cytidine 3',5'-monophosphate phosphodiesterase in Morris hepatomas having varying growth rates. 630 41

Autophosphorylation of the insulin receptor was studied using a glycoprotein fraction solubilized and purified partially from the rat hepatoma cell line, Fao. Incubation of this receptor preparation with [gamma-32P] ATP, Mn2+, and insulin yielded a single insulin-stimulated phosphoprotein of Mr = 95,000 which corresponds to the beta-subunit of the insulin receptor. At 22 degrees C, incorporation of 32P was half-maximal at 30 s and about 90% complete after 2 min. At steady state, about 200 pmol of 32P were incorporated per mg of protein; this value corresponded to about 2 molecules of phosphate per insulin binding site estimated from Scatchard plots. Insulin increased the Vmax for autophosphorylation of the insulin receptor kinase nearly 20-fold with no effect on the Km for ATP. Mn2+ stimulated autophosphorylation by decreasing the Km of the kinase for ATP, whereas Mg2+ had no effect. Dilution of the insulin receptor over a 10-fold concentration range did not decrease the rate of autophosphorylation suggesting that it may occur by an intramolecular mechanism. When the phosphorylated beta-subunit of the insulin receptor was digested with trypsin, at least 5 phosphopeptides could be separated by high performance liquid chromatography on a mu Bondapak C18 reverse-phase column. Insulin stimulated the phosphorylation of all sites. These phosphate acceptor sites varied in their rate and degree of phosphorylation. Phosphopeptides pp4 and pp5 were phosphorylated very rapidly and reached steady state within 20 s, whereas phosphorylation of pp1 and pp2 required several minutes to reach steady state.
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PMID:Kinetic properties and sites of autophosphorylation of the partially purified insulin receptor from hepatoma cells. 636 36

Previous studies indicated that accumulation of alpha-fucosyl-GM1 (IV2FucII3NeuAcGgOse4Cer) and alpha-galactosyl-alpha-fucosyl-GM1 (IV3GalIV2FucII3NeuAcGgOse4Cer) occurs in precancerous livers of rats fed the chemical carcinogen N-2-acetylaminofluorene, before development of hepatoma. Both fucogangliosides were completely absent in normal rat liver as well as in livers of rats fed a nonhepatic carcinogen and tumor promoters (Holmes, E.H., and Hakomori, S. (1982) J. Biol. Chem. 257, 7698-7703). The enzymatic basis of the chemical changes described above is reported in this paper. The alpha-L-fucosyltransferase activity toward GM1 (II2NeuAcGgOse4Cer) as well as asialo-GM1 (GgOse4Cer) was almost undetectable in extracts from normal rat liver, but significant activity of this enzyme was detected in extracts of rat livers after 4 weeks of feeding a diet containing N-2-acetylaminofluorene. The same enzyme activity in cultured rat hepatoma cells was 18- to 47-fold higher than in N-2-acetylaminofluorene-fed rat liver. In contrast, alpha-galactosyltransferase activity with a broad substrate specificity was detected in normal as well as in N-2-acetylaminofluorene-fed liver, although the specific activity of this enzyme in Golgi membranes in precancerous liver was significantly higher than that of normal rat liver. Thus, the appearance of alpha-fucosyl-alpha-galactosyl-GMI in precancerous liver is due to an induction of synthesis of alpha-fucosyl-GMI which is the substrate for the normally existing alpha-galactosyltransferase. The activity of alpha-fucosyltransferase was highly specific toward a substrate structure Gal beta 1 leads to 3GalNAc beta 1 leads to R in GMI or asialo-GMI and showed an anomalous inhibition by a large variety of detergents tested. In contrast, the alpha-galactosyltransferase showed a wide substrate specificity, activated by detergents and Mn2+ ion. Membrane alterations in precancerous and malignant transformation of rat liver is associated with an induction of an unusual alpha-fucosyltransferase which is the key step in synthesis of both fucogangliosides.
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PMID:Enzymatic basis for changes in fucoganglioside during chemical carcinogenesis. Induction of a specific alpha-fucosyltransferase and status of an alpha-galactosyltransferase in precancerous rat liver and hepatoma. 640 18

Escherichia coli DNA polymerase I (Klenow fragment), DNA polymerase alpha from both calf thymus and human lymphoma cells and DNA polymerase beta from calf thymus and Novikoff hepatoma cells can incorporate nucleotides opposite N-guanin-8-yl-acetyl-2-aminofluorene in DNA. The polymerases incorporate dCTP opposite some AAF-dG lesions when Mg2+ is the divalent cation. Substitution of Mn2+ for Mg2+ broadens the specificity of insertion: E. coli DNA polymerase I (Klenow fragment) also inserts A, and at specific sites G or T; DNA polymerase alpha inserts any of the four dNTPs with A and C incorporated preferentially to G and T. Polymerase beta is specific, inserting mainly C even in the presence of Mn2+. The Km for addition of dATP opposite a lesion by E. coli polymerase I (Klenow fragment) in the presence of Mn2+ is about 0.5 mM. dNMPs increase the insertion of nucleotides opposite AAF-dG in the presence of Mg2+ and increase both the rate and number of sites at which incorporation occurs in the presence of Mn2+. dNTP alpha S and recA protein increase only the insertion of C. We suppose that the incorporation of dCTP reflects normal base-pairing with the AAF-deoxyguanine in the anti conformation, whereas insertion of the other nucleotides (including some of the C) reflects insertion opposite the AAF adduct in its preferred syn conformation. The fact that the DNA polymerase plays a role in determining the specificity of insertion opposite a lesion terminating DNA synthesis suggests that the spectrum of base substitution mutagenesis seen in vivo may reflect the properties of the protein components, including the polymerase, involved in bypass synthesis.
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PMID:A role for DNA polymerase in the specificity of nucleotide incorporation opposite N-acetyl-2-aminofluorene adducts. 649 59

The membrane-bound UDP-GalNAc:polypeptide N-acetylgalactosamine transferase from an ascites hepatoma, AH 66, has been purified 48,100-fold, mainly by affinity chromatography in aqueous Triton X-100 on apomucin (deglycosylated bovine submaxillary mucin) coupled to Sepharose. The purified preparation behaved homogeneously on gel filtration on Sephadex G-150 in aqueous Triton X-100 and on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with an apparent molecular weight of about 55,000. The enzyme requires Mn2+, and only UDP-GalNAc served as a sugar donor. Apomucin, A1 protein, kappa-casein, apofetuin, and apoantifreeze glycoproteins served as acceptors, but the rate and amount of the transfer varied considerably from one acceptor to another. The transfer reaction terminated at the level of glycosylation of from only a few to at most about 40% of the serine plus threonine residues from which mucin-type oligosaccharides had been removed. This indicates that the transferase requires a certain conformation surrounding the acceptor site, but suggests also that a special mechanism may be functioning in vivo for frequent glycosylation of the abundant serine plus threonine residues of mucins. Lacto-N-fucopentaose I, ceramide di- and trihexosides, and globoside were not acceptors.
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PMID:Purification and characterization of UDP-GalNAc:polypeptide N-acetylgalactosamine transferase from an ascites hepatoma, AH 66. 680 38

p44erk1 is a member of a family of tyrosyl-phosphorylated and mitogen-activated protein (MAP) kinases that participate in cell cycle control. A full-length erk1 cDNA was isolated from a human hepatoma cell line (Hep G2) library. The erk1 cDNA clone shared approximately 96% predicted amino acid identity with partial sequences of rodent erk1 cognates, and the erk1 gene was assigned to human chromosome 16 by hybrid panel analysis. Human erk1 expressed in Escherichia coli as a glutathione S-transferase fusion (GST-Erk1) protein was substantially phosphorylated on tyrosine in vivo. It underwent further autophosphorylation in vitro (up to 0.01 mol of P per mol) at the regulatory Tyr-204 site and at additional tyrosine and serine residues. Threonine autophosphorylation, presumably at the regulatory Thr-202 site, was also detected weakly when the recombinant kinase was incubated in the presence of manganese, but not in the presence of magnesium. Before and after cleavage of the GST-Erk1 protein with thrombin, it exhibited a relatively high level of myelin basic protein phosphotransferase activity, which could be reduced eightfold by treatment of the kinase with the protein-tyrosine phosphatase CD45, but not by treatment with the protein-serine/threonine phosphatase 2A. The protein-tyrosine kinase p56lck catalyzed phosphorylation of GST-Erk1 at two autophosphorylations sites, including Tyr-204, and at a novel site. A further fivefold stimulation of the myelin basic protein phosphotransferase activity of the GST-Erk1 was achieved in the presence of a partially purified MAP kinase kinase from sheep platelets. Under these circumstances, there was primarily an enhancement of the tyrosine phosphorylation of GST-Erk1. This MAP kinase kinase also similarly phosphorylated a catalytically compromised version of GST-Erk1 in which Lys-71 was converted to Ala by site-directed mutagenesis.
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PMID:Molecular cloning, expression, and characterization of the human mitogen-activated protein kinase p44erk1. 768 43

In order to clarify the factors contributing to the signal intensities (SIs) of HCC on T1-weighted images, the amount of water, lipid, copper (Cu), iron (Fe), and manganese (Mn) was determined in HCC and surrounding hepatic parenchyma of 13 patients. The relationships among these findings, the histopathologic findings, and the SIs of T1-weighted images were evaluated. Among the 13 HCC, 3 had a high SI, 5 were isointense, and 5 had a low SI on T1-weighted images compared to the surrounding hepatic parenchyma. The paramagnetic ions which contributed to the SI patterns were assumed to be Cu in HCC (38.0 +/- 62.4 micrograms/g ww), and Fe in the liver (61.1 +/- 42.4 micrograms/g ww) and HCC (40.0 +/- 34.3 micrograms/g ww). In 8 HCC with high- or isointensity, 2 were grades I, 5 were grade II, and one was grade III according to the Edmondson-Steiner's histopathologic classification. It is concluded that the SI patterns alone can not be a sign of low grade malignancy because of the existence of Fe in livers and HCC.
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PMID:MR imaging of hepatocellular carcinoma. Correlation of metal content and signal intensity. 771 Jul 97

HepG2 human hepatoma cells, labeled with [35S]sulfate in the presence of 10-30 micrograms/ml of cycloheximide, released up to 64% of the amount of free tyrosine-O-[35S]sulfate produced and released by cells labeled in the absence of cycloheximide. A time-course study revealed that, in cells incubated in medium containing [3H]tyrosine, free [3H]tyrosine-O-sulfate was produced within 5 min of incubation, whereas no [3H]tyrosine-sulfated proteins were detected until 20 min after the incubation had begun. Using 3'-phosphoadenosine, 5'-phospho[35S]sulfate as the sulfate donor, HepG2 cell homogenate was shown to contain enzymic activity catalyzing the sulfation of L-tyrosine with the formation of tyrosine-O-[35S]sulfate. Upon subcellular fractionation, the majority of the enzyme activity was found in the cytosolic fraction. The enzyme, designated tyrosine sulfotransferase, displayed the optimum activity at pH 8.0 in the presence of 10 mM Mn2+. Under optimum conditions, the apparent Km of the enzyme for L-tyrosine, at 4.5-microM concentration of 3'-phosphoadenosine, 5'-phosphosulfate, was determined to be 1.95 mM, while that for 3'-phosphoadenosine, 5'-phosphosulfate, at 1 mM L-tyrosine concentration, was 8.3 microM. The Vmax determined under these conditions was 1.05 pmol.min-1.mg protein-1. A tyrosine-dependence study showed that, for cells labeled with [35S]sulfate, the production and release of free tyrosine-O-[35S]sulfate appeared to proceed actively and increase proportionally to the L-tyrosine concentration when it was raised above a threshold level in the culture medium. These results may imply a possible involvement of sulfation in removing excess intracellular L-tyrosine.
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PMID:De novo sulfation of L-tyrosine in HepG2 human hepatoma cells and its possible functional implication. 800 47

Insulin receptors have been characterized in a cell line recently isolated from a chicken hepatoma (LMH). The binding of 125I-insulin to LMH cells or membranes displayed the expected criteria for insulin receptors: affinity, temperature dependency, curvilinearity of Scatchard plot, rank order of potency for insulin analogs and insulin induced down-regulation. The alpha-subunit of LMH cell insulin receptors exhibited a normal size of 135 kDa. Following autophosphorylation, LMH WGA-purified receptors revealed a 95 kDa beta-subunit and a 72 kDa protein (pp72). Both proteins were phosphorylated in a time-, insulin- (and insulin-like growth factor 1; IGF-1) and manganese-dependent manner, and were precipitated by antiphosphotyrosine and two anti-insulin receptor antibodies. The 72 kDa protein was not present under non-reducing condition PAGE or in normal chicken liver. These results strongly suggest that pp72 is either a truncated form of the insulin receptor beta-subunit specific to LMH cells or a degradation product. Lectin-purified insulin receptors from LMH cells or chicken liver membranes exhibited similar tyrosine kinase activity, using artificial substrate poly(Glu-Tyr) 4:1. Finally, amino acid uptake by LMH cells was insulin stimulatable.
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PMID:Insulin receptor and insulin sensitivity in a chicken hepatoma cell line. 827 26


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