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)

Compactin, an inhibitor of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase, decreased cholesterol synthesis in intact Hep G2 cells. However, after the inhibitor was washed away, the HMG-CoA-reductase activity determined in the cell homogenate was found to be increased. Also the high-affinity association of LDL (low-density lipoprotein) to Hep G2 cells was elevated after incubation with compactin. Lipoprotein-depleted serum, present in the incubation medium, potentiated the compactin effect compared with incubation in the presence of human serum albumin. Addition of either mevalonate or LDL prevented the compactin-induced rise in activities of both HMG-CoA reductase and LDL receptor in a comparable manner. It is concluded that in this human hepatoma cell line, as in non-transformed cells, both endogenous mevalonate or mevalonate-derived products and exogenous cholesterol are able to modulate the HMG-CoA reductase activity as well as the LDL-receptor activity.
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PMID:Effects of compactin, mevalonate and low-density lipoprotein on 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and low-density-lipoprotein-receptor activity in the human hepatoma cell line Hep G2. 608 62

The activity of membrane-bound enzyme gamma-glutamyl transferase (GGT) is twice increased in the liver of normal and tumour-bearing rats after hydrocortisone intramuscular injections (10 mg/kg body weight). At the same time GGT activity is not increased in serum and hepatoma G-27. The glutathione-reductase activity and contents of G-SH and G-S-S-G in the rat liver and hepatoma are not altered by Hydrocortisone action at the different means of hormone administration. Effect of hydrocortisone is studied also on the GGT activity in the liver of newborn rats. The stimulation of GGT activity by hydrocortisone is probably due to an induction of protein synthesis.
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PMID:[Effect of hydrocortisone on gamma-glutamyl transferase activity of the rat liver and hepatoma]. 615 85

Liver glutathione-peroxidase (L-GSH-Px) and glutathione-reductase (GSSG-Red) activities were measured in supernatants of liver tissues obtained from a total of 36 subjects. Sixteen of these patients had a functionally normal liver (control group), whereas of the remaining 20 patients, 10 were cirrhotic and 10 had a liver disease other than cirrhosis. The mean value of L-GSH-Px of the control group was 33.12 +/- 12.66 U/g protein, a value similar to that found in patients with liver disease. The L-GSH-Px of the control group was positively correlated with the age of the subjects (r = 0.620; p less than 0.02). In contrast, in patients with liver disease an opposite behaviour of the two parameters was noted (r = -0.497; p less than 0.05). L-GSH-Px activity tended to be higher in males than in females, whereas the erythrocyte glutathione-peroxidase (E-GSH-Px) of the same patients was higher in females, albeit not significantly. L-GSH-Px and E-GSH-Px were not correlated either in normal or in liver disease. The mean GSSG-Red of the control group was 40.63 +/- 11.10 U/g protein, which is not different from that of the group of liver patients. GSSG-Red was not correlated with L-GSH-Px or with the age of patients. In two patients with hepatoma, the GSH-Px activity of the cancer tissue was low and the GSSG-Red activity high.
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PMID:Glutathione-peroxidase and glutathione-reductase activities of normal and pathologic human liver: relationship with age. 625 11

Extensive studies have demonstrated that the normal inhibition of cholesterol synthesis by cholesterol feeding is decreased in all hepatomas studied in vivo. This loss of the normal feedback regulation of cholesterol synthesis has been shown to be due to the failure of cholesterol ingestion to inhibit the activity of hydroxymethylglutaryl (HMG)-CoA reductase. The basis for this absence of feedback control of cholesterogenesis is unknown. Studies to date have not demonstrated structural or kinetic differences between the HMG-CoA reductase of normal liver and hepatoma. The present study, however, demonstrates significant differences in the activation state of HMG-CoA reductase from normal liver and hepatoma. In normal liver only approximately 10-20% of the microsomal HMG-CoA reductase is in the dephosphorylated, active form while 80-90% is in the phosphorylated, inactive state. In contrast, in three different Morris hepatomas in vivo, from 53 to 73% of the HMG-CoA reductase is in the active state. That the increased activation state in hepatomas is a property of tumor tissue and is not solely due to rapid growth is demonstrated by the fact that in both fetal and regenerating liver an enhanced activation state of HMG-CoA reductase is not observed. Additionally, preincubation with magnesium and ATP results in the inhibition of HMG-CoA reductase both in tumor and in liver. Presumably, this decrease in HMG-CoA reductase activity is due to the phosphorylation of the enzyme. Similarly, the preincubation of tumor and liver microsomes with phosphatase results in an increase in HMG-CoA reductase activity presumably by the dephosphorylation of the enzyme to its active form. The relationship between the altered activation state of HMG-CoA reductase in hepatomas and the reduction in the feedback regulation of this enzyme in liver tumors remains to be explored.
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PMID:Altered activation state of hydroxymethylglutaryl-coenzyme A reductase in liver tumors. 660 22

The metabolism of deoxycytidine (dCyd) and dCyd nucleotides in Yoshida ascites sarcoma (YS) cells and the host rat liver was investigated with reference to the increased excretion of urinary dCyd. Incorporation of [14C]orotic acid into the livers of rats at the fifth day after the transplantation of YS cells, the time when the amount of excretion of dCyd in urine was near maximal, was 2 times higher than that into the normal rat livers. After the injection of [14C]orotic acid, the ratio of the specific radioactivity of cytidylate to uridylate moieties of the host liver RNA was measured and found to be higher than that of normal rat liver RNA and to be similar to that of YS cell RNA. When [14C]orotic acid was injected into rats followed by the transplantation of YS cells, the radioactivities present in the livers disappeared more rapidly than those in the control rat livers. The activities of pyrimidine de novo synthesis enzymes, such as cytidine triphosphate synthetase (EC 6.3.4.2) and cytidine diphosphate reductase (EC 1.17.4.1), in YS were higher than those in both rat ascites hepatoma AH 7974 and Walker 256 carcinosarcoma, the transplantations of which did not induce increased excretion of dCyd into urine of the hosts. The activities of dCyd kinase (EC 2.7.1.10) and dCyd deaminase (EC 3.5.4.5) in YS cells were lower than those in the other two tumors investigated. The activities of cytidine triphosphate synthetase and cytidine diphosphate reductase in the livers of YS-bearing rats were elevated compared with those in the livers of rat ascites hepatoma AH 7974- or Walker 256 carcinosarcoma-bearing rats and normal rats, while the activities of dCyd kinase, 5'-nucleotidase (EC 3.1.3.5), and dCyd deaminase were similar between normal rat livers and tumor-bearing rat livers. These results suggest that the increased excretion of urinary dCyd in YS-bearing rats could be caused by both the stimulation of the synthesis of dCyd nucleotides and the low activity of dCyd deaminase in YS cells as well as in the host liver.
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PMID:Origin of increased deoxycytidine excretion into urine of rats bearing Yoshida ascites sarcoma. 672 78

NADPH-cytochrome P-450 reductase was purified to homogeneity from hepatoma 5123t.c.(H) microsomes from phenobarbital and hydrocortisone-treated rats by detergent solubilization and affinity chromatography with an overall 8% recovery. The purified enzyme has a minimum subunit molecular weight of 79 000 and contains one molecule each of FMN and FAD per 79 000 molecular weight. The purified hepatoma cytochrome P-450 reductase catalyzes electron transfer to artificial electron acceptors with Km values similar to those of purified liver reductase. The Km value of the hepatoma reductase for NADPH, 13 microM, is also similar to that of purified liver reductase. The tumor reductase appears immunochemically identical to liver reductase by Ouchterlony double-diffusion analysis and inhibition of activity. Peptide maps of the hepatoma and hepatic enzymes after proteolysis demonstrate the identity of the two proteins.
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PMID:Preparation of homogeneous NADPH-cytochrome P-450 reductase from rat hepatoma. 681 99

The effect of i.v. injection of mevalonate on the activity of microsomal 3-hydroxy-3-methylglutaryl Coenzyme A reductase was studied in livers from non-tumor-bearing rats and in host liver and hepatomas from rats bearing transplantable Morris hepatoma 7800. We confirmed that a single bolus injection of 100 mg of mevalonate in non-tumor-bearing male rats caused a 90% inhibition of hepatic 3-hydroxy-3-methylglutaryl Coenzyme A reductase activity within 2 hr. In two experiments mevalonate injection caused a 50 to 60% reduction in enzyme activity of hepatomas but no significant decline in the enzyme activity in host livers. Thirty in after injection of [14C]mevalonate in a similarly sized bolus, the ratio of specific activities of cholesterol in liver:hepatoma:kidney:blood was 13:5.6:0.5:1. Thus, both the liver and hepatoma efficiently utilized mevalonate for the synthesis of cholesterol. The precise cause of the inhibition of enzyme activity in the liver of non-tumor-bearing rats and in the transplantable hepatomas is not clear from this study. However, on the basis of other published reports, we suggest that it resulted from the accumulation of endogenous cholesterol in microsomal membrane. The activity of cholesterol 7 alpha-hydroxylase, the rate-controlling enzyme for bile acid synthesis, was also studied in the hepatoma, but, in general, it did not differ from that in the host liver or control liver.
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PMID:Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in Morris hepatoma 7800 after intravenous injection of mevalonic acid. 743 3

A plasmid expression system has been developed which allows sequence-specific effects on mRNA degradation rates to be determined. This system uses stable, nonintegrating vectors that provide consistent levels of mRNA expression without the position effects common to integrating vectors. cDNAs encoding putative instability elements may be subcloned into the 5' untranslated region (5'UTR), the coding region, or the proximal 3'UTR of a beta-globin cDNA reporter. The effects of these sequences on mRNA stability may then be determined by actinomycin time course analyses of the fusion mRNAs and recombinant beta-globin mRNA in human cell lines. To demonstrate the utility of the vector system we fused an 820-bp fragment of the cDNA encoding the proximal 3'UTR of human 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase to the 3'UTR of the beta-globin reporter and introduced the vector into the human hepatocarcinoma cell line, HepG2. The fusion mRNA was degraded at a rate 2- to 2.5-fold greater than that of beta-globin alone, at a rate similar to that reported for HMG CoA reductase mRNA in normal rat liver. Similar to a number of other relatively unstable mRNAs, the rate of fusion mRNA degradation was greatly decreased by treatment with cycloheximide.
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PMID:An episomal expression vector system for monitoring sequence-specific effects on mRNA stability in human cell lines. 756 67

Incubation of leukotriene B4 (LTB4) with Hep G2 cells (a human-derived hepatoma cell line) resulted in the production of several metabolites indicative of alternative pathways of LTB4 metabolism not previously observed in normal hepatocytes. The major extracellular LTB4-derived metabolites were structurally identified using mass spectrometry and ancillary techniques including electrospray ionization. The major metabolite was 10-hydroxy-4,6,8,12-octadecatetraenoic acid (10-HOTE), an unexpected metabolite which lost the hydroxy group at carbon 5 from the parent LTB4. Two other major metabolites were 3(R)-hydroxy-LTB4 and 3(S)-hydroxy-LTB4. The formation of these three metabolites revealed that beta-oxidation from the carboxyl terminus can be a significant metabolic pathway for degradation of this hydroxy unsaturated fatty acid. The normal hepatocyte LTB4-derived metabolite, 20-carboxy-LTB4, was observed as only a minor product. The metabolic profile for Hep G2 cells suggests that the efficient cytochrome P-450 pathway involved in omega-oxidation in typical hepatocytes is absent in these cells. Several minor metabolites were also identified which included dihydro products resulting from metabolism by a 12-hydroxydehydrogenase/delta 10-reductase pathway. The formation of the major metabolite reveals the operation of steps in beta-oxidation of hydroxy, unsaturated fatty acids not anticipated by previously identified steps of fatty acid beta-oxidation.
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PMID:Metabolism of leukotriene B4 in cultured hepatoma cells. 764 63

The intermediate metabolic events which degrade hydroxy polyunsaturated fatty acids is largely unknown. Such molecules are common products of lipid peroxidation and lipoxygenase catalyzed oxidation of arachidonic acid. Metabolism of two 5,12-dihydroxyeicosatetraenoic acids, 6-trans-LTB4 (leukotriene B4), and 6-trans-12-epi-LTB4 was studied in HepG2 cells (a human-derived hepatoma cell line). Extensive metabolism was observed with a major metabolite identified as 4-hydroxy-6-dodecenoic acid for both epimers. Incubation of 6-trans-LTB4 epimers at shorter times revealed the formation of intermediate metabolites, including 6-hydroxy-4,8-tetradecadienoic acid and 8-hydroxy-4,6,10-hexadecatrienoic acid suggesting beta-oxidation as the major pathway leading to the formation of the common terminal metabolite. Two additional metabolites were structurally elucidated as 5-oxo-6,7-dihydro-LTB4 and 6,7-dihydro-LTB4 which have not been previously described. Formation of 5-oxo-6,7-dihydro-LTB4 and 6,7-dihydro-LTB4 were also observed during metabolism of 6-trans-12-epi-LTB4 in human polymorphonuclear leukocytes. Of particular interest is the metabolism of these compounds by beta-oxidation from the carboxyl terminus, a process which is not observed with leukotriene B4 or leukotriene C4. Identification of these metabolites suggested the operation of the 5-hydroxyeicosanoid dehydrogenase pathway followed by a delta 6-reductase metabolic pathway which has not been previously described. This pathway of beta-oxidation may limit the activity of various 5,12-diHETEs including nonenzymatic hydrolysis products of LTA4 and also the recently described B4-isoleukotrienes.
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PMID:Metabolism of 6-trans-isomers of leukotriene B4 in cultured hepatoma cells and in human polymorphonuclear leukocytes. Identification of a delta 6-reductase metabolic pathway. 764 96


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