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)

Poly(adenosine diphosphoribose) (ADPR) synthase activities of nuclei isolated from normal human and leukemic leukocytes were assayed by incubation with radioactive NAD+. The synthase activity of leukemic leukocyte nuclei was significantly higher than that of normal leukocyte nuclei. The average length of polymers formed by isolated leukemic nuclei under the prescribed experimental condition ranged from 3.1 to 5.3 ADPR residues per chain, while those produced by normal leukocytes nuclei was 1.7 and 2.6 residues per chain. Isolated leukemic and normal leukocyte nuclei were incubated with and without NAD+ and the ability to carry out DNA synthesis was measured. The endogenous DNA synthesis of NAD-treated and untreated nuclei was the same. This finding parallels the result obtained with Novikoff hepatoma cell nuclei and differs from the observation with rat liver or testis nuclei.
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PMID:Poly (adnenosine diphosphoribose) synthase activity of isolated nuclei of normal and leukemic leukocytes. 17 Jun 27

1. A series of aldehyde dehydrogenase isozymes (aldehyde:NAD (P)+ oxidoreductase, EC 1.2.1.5), has been purified from hepatomas induced in Sprague-Dawley rats by 2-acetylaminofluorene. 2. The functional hepatoma-specific aldehyde dehydrogenase isozymes exist as 105 000-dalton dimers composed to two subunits of 53 000 daltons. Isoelectric points of the purified isozymes are 6.9-7.2. 3. Antiserum to these purified hepatoma-specific aldehyde dehydrogenases has been produced and the immunological relationships of these isozymes to their normal liver counterpart have been studied. Results of Ouchterlony double diffusions, agar-gel immunoelectrophoresis and polyacrylamide gel and agar immunoelectrophoresis indicate that anti-hepatoma aldehyde dehydrogenase antiserum cross-reacts with normal liver aldehyde dehydrogenase.
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PMID:Purification and immunochemical characterization of aldehyde dehydrogenase from 2-acetylaminofluorene-induced rat hepatomas. 18 64

Previously, we reported that the properties or microsomal 4-methyl sterol demethylase isolated from liver and Morris hepatomas 5123C and 7777 are grossly similar. The individual enzymic steps of this multicomponent system have now been studied, and the rate-determining step has been determined and shown to be identical for liver and these hepatomas. The rates of microsomal oxidative attacks of the 4alpha-methyl, 4alpha-hydroxymethyl, and 4-aldehydic groups are similar for microsomes prepared from rat liver and hepatoma 7777. The rates of mixed-function oxidative attack appear to increase in the order;--CH3 less than --CH2OH less than --CHO. Furthermore, the hepatic and hepatoma NAD-dependent decarboxylase, which catalyzes the reaction following the three oxidative attacks is similar in properties and velocity. The fifth step, an NADPH-dependent reduction of the 3 ketosteroid that is produced by decarboxylation, is also similar. For both tissues, the latter two reactions, under in vitro conditions, proceed at rates that exceed the initial oxidative process. Thus, for elimination of both of the 4-methyl groups of lanosterol, the 10 individual reactions catalyzed in this multicomponent system are identical in liver and hepatoma 7777 microsomes, and the rate-determining stop for both liver and hepatoma is the inital oxidative attack on the 4alpha-methyl group of cholesterol procursors. When the rate-determining reaction of both liver and hepatoma 7777 microsomes is assayed at different temperatures, the same activation energies and the same characteristic breaks in the arrhenius plots are observed. Thus, for both liver and hepatoma, both the nature and the site of rate determination in this multienzymic system must be similar. Since the microsomal enzymes of liver nad hepatoma appear to be catalytically similar and rate determination appears to be similar, too, the characteristic lact of response of tumor microsomes to treatments in vivo that alter host liver microsomal demethylation activity suggests that the insensitivity of these tumors to dietary cholesterol should not be ascribed to alterations in the catalytic proteins. Evidence in this report suggests that the postmicrosomal supernatant fraction of both liver and hepatoma contains a cytosolic protein that may participate in the regulation of the rate-determining attack of 4alpha-methyl sterol substrates. Thus, either qualitative or quantitative differences between the postmicrosomal supernatant fractions obtained from liver and heptomas may account for the observed differences in rates of cholesterol biosynthesis.
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PMID:Investigation of the rate-determining microsomal reaction of cholesterol biosynthesis from lanosterol in Morris hepatomas and liver. 19 49

IMP dehydrogenase (EC 1.2.1.14) was purified 180-fold from rat liver and from the transplantable rat hepatoma 3924A. The enzymes from the two sources were apparently identical; they exhibited hyperbolic saturation kinetics and an ordered, sequential mechanism, and were subject to inhibition by a number of purine nucleotides. Km values for the substrates, IMP and NAD+, were 12 and 24 micrometer respectively. IMP dehydrogenase activity in a spectrum of rat hepatomas was increased, relative to normal liver, by 2.5--13-fold; these increases correlated with tumour growth rate. Activity in two rat kidney tumours was increased 3-fold relative to that in normal renal cortex; control of activity of this enzyme is apparently altered in neoplastic cells. After partial hepatectomy, IMP dehydrogenase activity began to rise 6 h after operation, reaching a peak of 580% of normal activity by 18 h. Activity in neonatal liver, however, was only slightly higher than that in the adult. Organ-distribution studies showed highest enzyme activities in spleen and thymus. In livers of rats starved for 3 days, where all enzymes, except those involved in gluconeogenesis, showed decreased activity IMP dehydrogenase activity was increased; this change was accompanied by a rise in hepatic GTP concentrations. It is concluded that IMP dehydrogenase is a key enzyme in the regulation of GTP production, and thus involved in regulation of nucleic acid biosynthesis. The increased activity of IMP dehydrogenase in liver of starved rats may be related to the requirements for GTP for gluconeogenesis.
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PMID:Partial purification, properties and regulation of inosine 5'phosphate dehydrogenase in normal and malignant rat tissues. 19 16

Cholera toxin, using [32P]NAD+ as substrate, specifically radiolabels at least two proteins in plasma membranes of wild type S49 mouse lymphoma cells. The toxin-specific substrates are detectable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis as bands corresponding to molecular weights of 45,000 and a doublet of 52,000 to 53,000. Membranes of two other cell types exhibit similar patterns of radiolabeled bands specifically produced by incubation with cholera toxin: the "uncoupled" variant S49 cell, which possesses adenylate cyclase activity unresponsive to hormones, and the HTC4 rat hepatoma cell, which lacks detectable catalytic adenylate cyclase activity but contains components of the cyclase system necessary for regulation by guanyl nucleotides and NaF. Little or no toxin-specific radiolabeling is observed in membranes of a fourth cell type, the adenylate cyclase activity-deficient S49 variant, which functionally lacks components of the cyclase system involved in cholera toxin action and regulation by guanyl nucleotides and NaF. The toxin-specific labeling pattern is not observed in membranes prepared from wild type S49 cells previously treated with cholera toxin in culture. One or both of the toxin substrates thus appears to be involved in regulation of adenylate cyclase by guanyl nucleotides and fluoride ion.
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PMID:Genetic evidence that cholera toxin substrates are regulatory components of adenylate cyclase. 21 17

The study of some NAD(P)H dehydrogenating enzymes in one slow- and one fast-growing transplantable hepatoma has shown that the activity of the soluble enzyme D-T diaphorase is increased several-fold when compared with the activity of the control livers. The increase in enzyme activity is similar in both hepatomas, regardless of the rate of growth of the tumors. The activity of the glycerolphosphate, malic and lactic dehydrogenases are decreased in both tumors. The possible functional significance of these changes is discussed in the text.
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PMID:The activity of the D-T diaphorase in experimental hepatomas. 61 21

1. The reoxidation of cytosolic NADH was studied in a line of human hepatoma cells (HuH13) whose mitochondria preferentially utilized glutamine for ATP formation. 2. The tumor cells showed mitochondrial reoxidation of NADH, as evidenced by the accumulation of pyruvate, when incubated aerobically with L-lactate. The involvement of the respiratory chain was demonstrated by the addition of specific inhibitors. 3. Glutamine oxidation proceeded in the tumor mitochondria exclusively via a pathway involving transamination. Malate stimulated aspartate production from glutamine. 4. When the tumor cells were cultured in Eagle's medium with aminooxyacetate or in the absence of glutamine, a marked reduction in the cellular NAD/NADH ratio was observed. 5. These results indicate that the malate-aspartate shuttle was functioning in the tumor cells.
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PMID:Oxidation of cytosolic NADH by the malate-aspartate shuttle in HuH13 human hepatoma cells. 131 Feb 90

In mouse hepatoma Hepa-1c1c7 cultures, polycyclic aromatic compounds such as benzol[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) activate the Cyp1a-1 (cytochrome P(1)450) and Nmo-1[NAD(P)H:menadione-oxidoreductase] genes, two members of the aromatic hydrocarbon (Ah)-responsive gene battery. Mevinolin is known to inhibit 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase (EC 1.1.1.34), the rate-limiting step in cholesterol biosynthesis. We show here that in the absence of TCDD, mevinolin markedly increases Cyp1a-1 transcription, CYP1A1 mRNA and protein levels and enzyme activity, and NMO1 mRNA concentrations. Addition of mevalonate, the product of HMG-CoA reductase activity, fails to reverse the effects of mevinolin. In fact, when used at high concentrations, mevalonate activates Cyp1a-1 transcription. Mevinolin-induced Cyp1a-1 gene activation: (1) occurs independently of the lipid content of the growth medium, (2) is not suppressed by adding 25-hydroxycholesterol, which blocks MHG-CoA reductase activity, and (3) requires a functional Ah receptor and unimpaired nuclear translocation of the receptor. It is possible that an unknown metabolite (or metabolites) of mevinolin activates Cyp1a-1 expression and that high concentrations of mevalonate act via the same mechanism. Using chimaeric plasmids that contain different lengths of Cyp1a-1 5' flanking regions fused to the bacterial neomycin (neo) gene, we find that the mevinolin effect on Cyp1a-1 induction requires the 5' flanking sequences between -1647 and -824, which are also needed for TCDD induction. Mevinolin, however, is not a ligand for the Ah receptor. Gel mobility shift assays revealed that Cyp1a-1 activation caused by mevinolin does not involve the ligand-dependent formation of a functional Ah receptor-dependent DNA-binding complex, but instead appears to be correlated with release of a putative repressor from its cognate DNA site. Our results suggest that the basel level of Cyp1a-1 transcription is maintained by an unknown negative regulatory factor. We propose that Cyp1a-1 transcriptional activation can result not only from induction by polycyclic aromatic compounds but also from derepression by mevinolin, independent of HMG-CoA reductase inhibition.
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PMID:Transcriptional derepression of the murine Cyp1a-1 gene by mevinolin. 131 Dec 72

Comparative investigation of different mitochondrial oxidative metabolism inhibitors action on NAD(P)H and flavoproteins fluorescence intensity of minimal transformed 3T3 NIH mouse fibroblasts and rat HTC hepatoma cells was made. Principle differences were shown between these cells in oxidized flavoproteins fluorescence intensity changes under the action of used inhibitors. It is suggested that the unusual HTC hepatoma cells flavin fluorescence intensity increase is connected with the oxidation of unidentified flavin-containing component functionally attached to mitochondrial respiratory chain.
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PMID:[A comparative analysis of the action of oxidative metabolic inhibitors on the luminescence parameters of normal and tumorous cells]. 144 Sep 28

Deletion mutagenesis in human NAD(P)H:Quinone Oxidoreductase (NQO1) gene and transfection studies into mammalian cells identified a segment of DNA designated as human Antioxidant Response Element (hARE) responsible for high basal expression in tumor cells and its induction by beta-naphthoflavone (beta-NF). The twenty four base pairs of the hARE contains an essential cis-element AP1 binding site and has been shown to bind to jun-D and c-fos proteins from mouse hepatoma (Hepa-1) nuclear extract. In the present report, we have identified jun-B as the third major protein in the hARE-Hepa-1 proteins complex observed in the band shift assays.
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PMID:Identification of jun-B as third member in human antioxidant response element-nuclear proteins complex. 144 67


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