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(A) polymerases (PAPs) from HeLa cell cytoplasmic and nuclear fractions were extensively purified by using a combination of fast protein liquid chromatography and standard chromatographic methods. Several forms of the enzyme were identified, two from the nuclear fraction (NE PAPs I and II) and one from the cytoplasmic fraction (S100 PAP). NE PAP I had chromatographic properties similar to those of S100 PAP, and both enzymes displayed higher activities in the presence of Mn2+ than in the presence of Mg2+, whereas NE PAP II was chromatographically distinct and had approximately equal levels of activity in the presence of Mn2+ and Mg2+. Each of the enzymes, when mixed with other nuclear fractions containing cleavage or specificity factors, was able to reconstitute efficient cleavage and polyadenylation of pre-mRNAs containing an AAUAAA sequence element. The PAPs alone, however, showed no preference for precursors containing an intact AAUAAA sequence over a mutated one, providing further evidence that the PAPs have no intrinsic ability to recognize poly(A) addition sites. Two additional properties of the three enzymes suggest that they are related: sedimentation in glycerol density gradients indicated that the native size of each enzyme is approximately 50 to 60 kilodaltons, and antibodies against a rat hepatoma PAP inhibited the ability of each enzyme to function in AAUAAA-dependent polyadenylation.
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PMID:Multiple forms of poly(A) polymerases purified from HeLa cells function in specific mRNA 3'-end formation. 255 86

A sphingomyelinase, which specifically hydrolyzes sphingomyelin into ceramide and phosphocholine, was solubilized from nuclear matrix fraction of rat ascites hepatoma, AH7974 cells. The solubilized enzyme was subjected to Mono Q column chromatography in an FPLC system. The sphingomyelinase which was adsorbed on the column and eluted at 0.25-0.5 M NaCl was characterized. The enzyme required 10 mM MgCl2, 0.01% Triton X-100, 1 mM dithiothreitol, and a higher concentration of buffer than 1 M for its maximal activity, and the optimal pH was 6.7-7.2 in 2 M Tris/acetic acid or 7.5 in 2 M potassium acetate/acetic acid. N-Ethylmaleimide completely inhibited the enzyme activity at 0.2 mM. Therefore, this enzyme is classified as a Mg2+-dependent, neutral sphingomyelinase. The sphingomyelinase sedimented at 4.3S through a 10-30% glycerol gradient containing 2 M potassium acetate. This enzyme was highly specific to sphingomyelin and did not hydrolyze phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. Various characteristics of the nuclear sphingomyelinase were similar to those of the plasma membrane enzyme except its requirement for a high concentration of buffer and SH-reagent.
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PMID:Existence of Mg2+-dependent, neutral sphingomyelinase in nuclei of rat ascites hepatoma cells. 255 12

6-Phosphofructo-2-kinase was purified from rat liver and hepatoma (HTC) cells. The HTC cell enzyme had kinetic properties different from those of the liver enzyme (more sensitive to inhibition by citrate and not inhibited by sn-glycerol 3-phosphate) and was not a substrate of the cyclic-AMP-dependent protein kinase. Unlike the liver enzyme, which is bifunctional and phosphorylated by fructose 2,6-[2-32P]bisphosphate, the HTC cell enzyme contained no detectable fructose-2,6-bisphosphatase activity and phosphorylation by fructose 2,6-[2-32P]-bisphosphate could not be detected. HTC cell fructose-2,6-bisphosphatase could be separated from 6-phosphofructo-2-kinase activity by purification. Antibodies raised against liver 6-phosphofructo-2-kinase did not precipitate HTC cell fructose-2,6-bisphosphatase whose kinetic properties were completely different from those of the liver enzyme.
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PMID:Rat hepatoma (HTC) cell 6-phosphofructo-2-kinase differs from that in liver and can be separated from fructose-2,6-bisphosphatase. 284 Nov 25

The lipid compositions of homogenates and microsomal fractions derived from surgical samples of highly differentiated human hepatoma, morphologically normal regions outside the tumours and from normal livers were analysed. A few enzyme activities were also assayed. Hepatoma microsomes demonstrated considerably lowered levels of cytochromes P-450 and b5. Hepatoma homogenates exhibited increased levels of cholesterol, normal amounts of dolichyl-P and slightly lowered levels of total phospholipid. The levels of dolichol, dolichol ester and ubiquinone in hepatoma homogenates were prominently decreased. In tumour microsomes the levels of cholesterol and dolichyl phosphate were increased considerably while the levels of phospholipid and dolichol were lowered. The phospholipid composition of tumour homogenates was roughly similar to that of control tissue. In tumour microsomes the relative amounts of phosphatidylserine and phosphatidylinositol were about 30% decreased, whereas the major phospholipids showed minor increases in amount. The rate and pattern of incorporation of [3H]glycerol into individual phospholipids in liver slices from control and hepatoma tissue did not differ to any larger extent. The fatty acid composition of tumour homogenates exhibited minor differences in comparison to the control with the greatest changes in the sphingomyelin fraction. In hepatoma microsomes the fatty acid compositions of the major phospholipids were altered moderately, with evident decreases in the relative amounts of the long-chain polyunsaturated fatty acids. In hepatoma homogenates the fatty acid composition of dolichol esters differed only slightly from the control pattern. These results indicate that the major disturbance in the lipid metabolism of highly differentiated hepatomas is localized to the mevalonate pathway, thus affecting mainly the levels of cholesterol, dolichol and ubiquinone.
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PMID:The lipid composition of highly differentiated human hepatomas, with special reference to fatty acids. 284 69

The consumption of long chain polyunsaturated fatty acids by fish oils leads to profound lowering of plasma triacylglycerol but not of plasma cholesterol. Reasons for this were investigated with the human hepatoma cell line, the Hep G2 cell. Incubations with oleic acid (18:1 n9), linoleic acid (18:2 n6) and the characteristic marine fatty acid eicosapentaenoic acid (EPA, 20:5 n3) enriched cellular triacylglycerol mass, though least with EPA. However, secretion of very low density lipoprotein (VLDL) triacylglycerol and apoprotein B (measured by formation from [3H]glycerol and [3H]leucine) was markedly inhibited by EPA. Preincubation with linoleic acid reduced VLDL triacylglycerol but not apo B secretion in comparison with oleic acid which stimulated both. A possible effect on low density lipoprotein (LDL) removal was studied by measuring [125I]LDL binding. Preincubation with either EPA or linoleic acid inhibited the saturable binding of LDL, observed with oleic acid and control incubations. The binding of lipoproteins containing chylomicron remnants was not affected by any of the fatty acids.
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PMID:Eicosapentaenoic acid inhibits the secretion of triacylglycerol and of apoprotein B and the binding of LDL in Hep G2 cells. 303 33

The role that protein kinase C (PKC) may play on insulin regulation of glucose metabolism was investigated in rat adipocytes and Zajdela hepatoma cultured (ZHC) cells which are two cell types highly responsive to insulin. In rat adipocytes, 4 beta-phorbol 12 beta-myristate, 13 alpha-acetate (PMA, 0.1-1,000 ng/ml), a potent tumor promoter acting as a substitute for diacylglycerol which directly activates PKC, stimulated basal 2-deoxyglucose (2-DG) transport in a time- and dose-dependent manner, but decreased the activation of this process elicited by submaximal concentrations of insulin. PMA (0.1-1,000 ng/ml) also stimulated basal lipogenesis from [3-3H] glucose in a dose-dependent manner. Maximal PMA and insulin effects on both processes were not additive. The specificity of the insulin-like effects of PMA was assessed by the finding that 4 beta-phorbol 12, 13 dibutyrate (PDBu), mezerein, 1-oleyl-2-acetyl glycerol (OAG) and 1, 2 diolein, know as PKC activators, also markedly stimulated glucose metabolism whereas 4 alpha-phorbol 12, 13 didecanoate (4 alpha-PDD) and 4 beta-phorbol 13-monoacetate, shown not to activate PKC, were ineffective. PMA and insulin biological effects exhibited several similarities: both agents stimulated glucose transport and lipogenesis in a calcium-dependent manner, both activated glucose transport through an energy-requiring process, and the effects of both were markedly decreased by mellitin, a PKC inhibitor. Finally, fat cells made PKC-deficient by a chronic treatment with PMA exhibited a marked decrease in insulin responsiveness for stimulation of glucose transport and lipogenesis, with no change in either the hormone sensitivity or the insulin receptor affinity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Regulation of glucose metabolism by insulin: dual role of protein kinase C]. 305 80

Rat liver cytosol has low hydrolytic activity against [3H]methylcasein at neutrality, but activity increases greatly on addition of various compounds such as poly-L-lysine, N-ethylmaleimide, and sodium dodecyl sulfate, suggesting that it contains latent proteolytic activity. The latent enzyme was found to be stabilized in the presence of 20% glycerol and to be activated by addition of poly-L-lysine. The latent enzyme was purified from a crude extract of rat liver to apparent homogeneity in the presence of 20% glycerol by conventional chromatographic techniques. The purified enzyme showed endoproteolytic activity toward various proteins when it was activated by the compounds listed above. It preferentially degraded N-substituted tripeptide substrates with a basic amino acid at the carboxyl terminus, as well as peptides containing neutral hydrophobic amino acids. It did not require activation for these peptidase activities, in contrast to its activity toward large proteins. Interestingly, a proteinase and a trypsin-like and a chymotrypsin-like peptidase activity could not be separated by customary chromatographic methods but were distinguishable by their sensitivities to various inhibitors, activators, and covalent modifiers, suggesting that the enzyme has three distinct active sites within a single protein. The enzyme seems to be a seryl endopeptidase showing maximal activity at neutral and weakly alkaline pH values. Thus, the enzyme is a unique protease with latent multifunctional catalytic sites. The distribution of the protease in soluble extracts of various rat tissues and cells was examined quantitatively by an enzyme immunoassay. The enzyme level was highest in liver and also in spleen, stomach, lung, small intestine, and kidney, but was low in heart, diaphragm, skeletal muscle, brain, and skin. The concentrations of enzyme in some established cell lines including hepatoma and rat kidney cells were comparable to that in normal liver hepatocytes. The enzyme was found mainly in the cytosol fraction, although a small amount was associated with microsomal membranes, suggesting that it is an extralysosomal protease. Immunohistochemical staining of the liver and skeletal muscles showed that the protease is distributed diffusely in panlobular hepatocytes with slight centrilobar predominance and is present in Kupffer cells, vascular endothelial cells, and bile duct epithelial cells in the liver and also diffusely in the intermyofibrillar spaces and vascular endothelial cells in skeletal muscle. The quantitative data obtained in the present study indicate the presence of the protease in the cytosol fraction of all rat tissues.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A high molecular weight protease in the cytosol of rat liver. I. Purification, enzymological properties, and tissue distribution. 309 25

This study identifies and partially characterizes an insulin-sensitive glycophospholipid in H35 hepatoma cells. The incorporation of [3H]glucosamine into cell lipids was investigated. A major labeled lipid was purified by sequential thin layer chromatography using first an acid followed by a basic solvent system. After hydrochloric acid hydrolysis and sugar analysis by thin layer chromatography, 80% of the radioactivity in the purified lipid was found to comigrate with glucosamine. H35 cells were prelabeled with [3H]glucosamine for either 4 or 24 h and treated with insulin causing a dose-dependent stimulation of turnover of the glycophospholipid which was detected within 1 min. The purified glycolipid was cleaved by nitrous acid deamination indicating that the glucosamine C-1 was linked to the lipid moiety through a glycosidic bond. [14C]Ethanolamine, [3H]inositol, and [3H]sorbitol were not incorporated into the purified glycolipid. The incorporation of various fatty acids into this glycolipid was also studied. [3H]Palmitate was found to be preferentially incorporated while myristic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, and arachidonic acid were either not incorporated or incorporated less than 10% of palmitate. The purified glycolipid labeled with [3H]palmitate was cleaved by treatment with phospholipase A2 but was resistant to mild alkali hydrolysis suggesting the presence of a 1-hexadecyl,2-palmitoyl-glyceryl moiety in the purified lipid. Treatment of labeled glycophospholipid with phosphatidylinositol-specific phospholipase C from Staphylococcus aureus generated a compound migrating as 1-alkyl,2-acyl-glycerol and a polar head group with a size in the range from 800 to 3500. These findings coupled with the nitrous acid deamination demonstrate that glucosamine was covalently linked through a phosphodiester bond to the glyceryl moiety of the purified glycolipid. These findings suggest that insulin acts on this glycophospholipid by stimulating an insulin-sensitive phospholipase C. This unique glycophospholipid may play an important role in insulin action by serving as precursor of insulin-generated mediators.
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PMID:Identification of a novel insulin-sensitive glycophospholipid from H35 hepatoma cells. 354 86

The intracellular membranes of hepatomas exhibit an altered content and composition of lipid compared to the membranes of normal liver. In order to elucidate the role of lipid biosynthetic enzymes in these membrane differences, we first examined the fatty acyl-CoA ligase and acyl-CoA:sn-glycerol 3-phosphate (Gro-3P) acyltransferase activities and acyl specificities of microsomes from liver, Morris hepatoma 7288C, and hepatoma tissue culture (HTC) cells. Based upon incorporation of fatty acid and Gro-3P, it is concluded that acyl-CoA:sn-Gro-3P acyltransferase activities are markedly elevated (6-30-fold) in the microsomes of Morris Hepatoma 7288C and HTC cells compared to microsomes from liver, whereas the fatty acyl-CoA ligase activity is reduced (30-50-fold). Therefore, the low phospholipid content of these tumor cells does not appear to result from reduced acyltransferase activity. Though diminished ligase activity may play a role, it appears that activation of fatty acid may not be rate-limiting, even at the low levels of fatty acyl-CoA ligase present in the tumor and HTC cells. Preliminary evidence suggests that another factor that may be responsible for the low tumor phospholipid content is the limited availability of Gro-3P, a lipid precursor. The phospholipid in hepatoma 7288C is also characterized by an elevated ratio of monenoic to dienoic fatty acid. We have found that this change does not reflect an altered specificity of acyl-CoA:sn-Gro-3P acyltransferase.
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PMID:Biosynthesis of glycerolipids by hepatoma and liver microsomes. I. Fatty acyl-CoA ligase and acyl-CoA:sn-glycerol-3-phosphate acyltransferase. 380 1

The effects of acute diabetes mellitus on the growth of Morris hepatoma 7288CTC and Jensen sarcoma were studied in fed, young (less than 200 g), and adult (greater than 250 g) rats. Animals were matched for tumor size and growth; the rates of tumor growth were the same in fed, young and adult nondiabetic rats. Diabetes was induced by the i.v. injection of streptozotocin (65 mg/kg total body weight) into tumor-bearing rats and changes in arterial blood nutrient concentrations were compared to changes in the rates of tumor growth and DNA synthesis. In young rats acute diabetes did not increase the blood concentrations of the fat store-derived nutrients and did not increase the rate of tumor growth. In adult rats, however, acute diabetes raised the arterial blood free fatty acid, glycerol, triglyceride, and ketone body concentrations to high levels and increased the rate of tumor growth about three times over that observed in untreated rats. Progress curves for the mobilization of host fat stores and for incorporation of [methyl-3H]thymidine into tumor DNA during the onset of diabetes showed that these activities were closely correlated in adult rats. Both processes began to increase 2 to 4 h after streptozotocin treatment, reached an initial peak at 12 to 16 h, decreased to a low point at 18 to 20 h, and then increased again to the new steady state after 23 to 24 h. The results indicate that the rate of tumor growth in rats in vivo is limited by the availability of a substance(s) present in the hyperlipemic blood of adult diabetic rats. The tight relationship between host lipolysis and tumor growth suggests that the substance(s) is derived from host fat stores.
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PMID:Stimulation of tumor growth in adult rats in vivo during acute streptozotocin-induced diabetes. 381 72


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