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)

DEAE-Bio-Gel chromatography of 100,000 X g supernatant from cultured HTC hepatoma cells separated cyclic nucleotide phosphodiesterase into three forms, numbered E I, E II, and E III in order of elution from the column, E I had a low Km for cyclic guanosine 3':5'-monophosphate (cGMP) and a high Km for cyclic adenosine 3':5'-monophosphate (cAMP), E II exhibited anomalous kinetics. At low substrate concentrations (0.5 muM) cGMP was hydrolyzed more rapidly than cAMP and hydrolysis of 0.5 muM cAMP was stimulated by 1 muM cGMP. E III had a low Km for cAMP. Incubation of cells with 1 muM dexamethasone for 72 h decreased the activity of E I and E II. In cells incubated with N6,O2'-dibutyryl cAMP plus 3-isobutyl-1-methylxanthine for 14 h the activity of E III was increased approximately 100%. Similar activities of calcium-dependent, heat stable phosphodiesterase activator were recovered from supernatants from all cells. These studies have established the presence, in a homogeneous population of hepatoma cells, of at least three forms of cyclic nucleotide phosphodiesterase, the activities of which can be independently regulated.
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PMID:Regulation of cyclic nucleotide phosphodiesterases in cultured hepatoma cells by dexamethasone and N6,O2'-dibutyryl adenosine 3':k'-monophosphate. 19 Feb 34

Recently, it was shown that lipoprotein lipase (LPL) was produced in neonatal but not in adult rat liver. In an attempt to further define the mechanism involved in liver LPL expression, we identified a neonatal mouse hepatoma cell line, BWTG3, capable of producing LPL. The regulation of LPL expression by various extracellular stimuli was investigated in this cell line. Progesterone caused a rise in LPL production by BWTG3 cells. Other hormones tested, such as insulin, glucagon, adrenalin, testosterone, and thyroid hormone, had no effect on LPL production. The effects of progesterone on LPL production showed slow kinetics reaching a maximum 24 h after addition. Cotransfection of a progesterone receptor expression vector with a 5'-LPL-CAT reporter construct resulted in an induction of CAT activity, suggesting that the increase in LPL accumulation after progesterone was linked to transcriptional induction of the LPL gene. Stimuli causing an elevation of protein kinase A activity in the cells also increased LPL production. Three agents capable of elevating intracellular cAMP levels, i.e., forskolin, dBcAMP, and choleratoxin, caused an elevation of LPL production. The increase in LPL activity caused by forskolin and choleratoxin was paralleled by an elevation of LPL mRNA levels, while dBcAMP only induced a small elevation of LPL mRNA levels. The increase in LPL production was shown to be linked to the stimulation of the PKA signal transduction pathway and was apparently transmitted via the transcription factor CREB. No effect of the stimulation of protein kinase C or calcium/calmodulin-dependent kinase on LPL production was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein lipase expression in undifferentiated hepatoma cells is regulated by progesterone and protein kinase A. 132 33

ML-9, an inhibitor for myosin light chain kinase, and W-7, a calmodulin inhibitor, suppressed the efflux of vinblastine and increased the intracellular accumulation of vinblastine, but W-5, an inactive compound for calmodulin, did not so in rat ascites hepatoma AH66 cells, which have a multidrug-resistant phenotype. In sensitive counterpart AH66F cells, W-7 and ML-9 were less effective. W-7 and ML-9 did not interfere with [3H]azidopine photolabeling of P-glycoprotein in the plasma membrane from AH66 cells. While P-glycoprotein is reported to be superphosphorylated by protein kinases, W-7 did not influence the phosphorylation of the P-glycoprotein in AH66 cells. There may be an unknown Ca(2+)-calmodulin-dependent mechanism in the extrusion of vinblastine from AH66 cells.
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PMID:Increase of vinblastine accumulation by inhibitors of calmodulin-dependent cell functions in rat ascites hepatoma AH66 cells. 136 14

The sera from patients with various liver diseases were investigated for the antibody against calmodulin (CaM) extracted from bovine brain by the enzyme linked immunosorbent assay. The specificity and purity of CaM were confirmed by the Western blot technique using anti-CaM antibody (anti-CaM) positive sera. IgA class antibody was frequently detected in patients with hepatocellular carcinoma (HCC), autoimmune hepatitis (AIH) and chronic active hepatitis (CAH). On the other hand, IgG class antibody was very often present in patients liver cirrhosis, AIH and acute viral hepatitis (AVH). Sixty seven percent of patients with AVH in the acute phase were positive for IgM class anti-CaM and 33% of patients with AVH in the convalescent phase positive respectively. In AVH, the titer of anti-CaM reached its peak on 26.3 days after the onset. The titer of anti-CaM in fulminant hepatitis was higher than that in AVH. Seventy percent of type A hepatitis patients were positive for IgM class anti-CaM, 33% of type B and 33% of type non-A non-B. These results suggest that the frequency and titer of anti-CaM may depend upon the type of hepatitis and the degree of liver cell injury.
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PMID:[Clinical significance of antibodies against calmodulin in patients with various liver diseases]. 203 May 58

A bacterial expression system for the parvalbumin-like calcium-binding protein oncomodulin has been constructed. This system can yield 50-fold more oncomodulin than the richest known mammalian source, the rat Morris hepatoma 5123. The bacterially produced protein folded correctly as monitored by UV, fluorescence, and 1H nuclear magnetic resonance spectroscopy and is immunologically identical to rat hepatoma oncomodulin. A calcium-specific conformational change is observed in the bacterial oncomodulin similar to that of the hepatoma protein. A modification of the putative calcium-specific CD loop by site-directed mutagenesis, which changed Asp-59 to Glu-59, eliminates calcium-specific effects. In contrast to the native molecule, the mutant Glu-59 now exhibits a magnesium-induced conformational change when monitored by UV difference or fluorescence excitation spectroscopy. The availability of large amounts of bacterially produced oncomodulin combined with the ability to modify at will the metal-binding ligands should now allow dissection of the unusual pairing in oncomodulin of one calcium-specific calmodulin-like site with one calcium/magnesium parvalbumin-like site.
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PMID:Characterization and site-specific mutagenesis of the calcium-binding protein oncomodulin produced by recombinant bacteria. 264 85

At non-cytotoxic concentrations, actions of smooth muscle relaxants except for the action of isoproterenol (IPN) on the effect of vinblastine (VBL) and mitomycin C (MMC) in rat ascites hepatoma AH66 cells resistant to these antitumor agents clearly separated into two groups. IPN hardly influenced the effects of both VBL and MMC. Although verapamil, a calcium-antagonist, and W-7, a calmodulin inhibitor, enhanced the growth-inhibitory effect and uptake of VBL by inhibiting the VBL efflux, these drugs did not influence the effect and uptake of MMC. In contrast, forskolin, an adenylate cyclase activator, db-cAMP, a cAMP analog, and theophylline, a cyclic nucleotide phosphodiesterase inhibitor, potentiated the effect of MMC, but did not influence the effect of VBL. The combination effect of forskolin and db-cAMP might be elucidated from the increase of inward transport of MMC through the action of the intracellular cAMP elevated by these drugs. Theophylline, however, only slightly increased both intracellular cAMP level and MMC uptake into the cells, similar to the action of IPN. We thought that the combination effect of theophylline was effected through its other activity of repair inhibition against AH66 cells, which are resistant to MMC due to their high capacity to repair impaired DNA. Thus, the smooth muscle relaxants used in this study enhanced the growth-inhibitory effect of a distinct antitumor agent through their individual activity against tumor cells.
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PMID:Multiform combination effects of smooth muscle relaxants with antitumor agents in rat ascites hepatoma AH66 cells. 282 96

Preincubation of hepatoma cells and human skin fibroblasts in the presence of the calmodulin antagonists trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide resulted in a dose-dependent suppression of [14C]mevalonolactone incorporation into cholesterol. At a calmodulin antagonist concentration of 25 mumol, the incorporation of [14C]mevalonolactone into cellular cholesterol was suppressed to about 30% (hepatoma cells) and 10% (human skin fibroblasts) of control values. When the total nonsaponifiable [14C]lipids were separated and analyzed by two-dimensional thin layer chromatography, an accumulation of [14C]desmosterol was observed along with reduced formation of [14C]cholesterol. However, when cells were preincubated in the presence of [14C]dihydrolanosterol, [14C]cholesterol formation was not inhibited by the calmodulin antagonists. About 25% of the cell-associated dihydrolanosterol radioactivity was converted to cholesterol in both control and calmodulin antagonist-pretreated cells. The data suggest that calmodulin antagonists prevent the conversion of desmosterol into cholesterol by inhibiting sterol delta 24 reductase and that the enzymes catalyzing sterol ring modifications are not affected by the inhibitors.
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PMID:Calmodulin antagonists suppress cholesterol synthesis by inhibiting sterol delta 24 reductase. 303 32

PLC/PRF/5 hepatoma cells cultured with a tumor promoter teleocidin showed polygonal cellular appearance with many vacuole-like structures, and reduced both c-myc mRNA level and growth rate. These teleocidin effects were partly mimicked by sodium butyrate but not by a protein kinase C stimulant 1-oleoyl-2-acetylglycerol(OAG). Protein kinase C inhibitor 1-(5-isoquinolinyl-sulfonyl)-2-methyl-piperazine(H7), calmodulin-dependent protein kinase antagonist N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide(W7) and topoisomerase II inhibitor novobiocin failed to inhibit the effects of teleocidin. These results may suggest the presence of still unknown biochemical pathways which mediate the actions of teleocidin.
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PMID:Effects of teleocidin on the morphology and c-myc expression of hepatoma cells which are not inhibited by protein kinase antagonists. 310 17

Plasma-membrane-bound kinases of AS-30D ascites from transplantable rat hepatocarcinoma were shown to extensively catalyze the phosphorylation of plasma membrane proteins and membrane lipids, using [gamma-32P]ATP or [gamma-32P]GTP as a phosphate donor. In contrast, plasma membranes from normal adult rat liver or fast-growing regenerating liver (24 h after partial hepatectomy) produce significantly less activity for protein phosphorylation and little phosphorylation of the lipids. However, neonatal (24 h old) rat liver plasma membrane preparations show levels of phosphorylation of proteins and lipids intermediate between those in the tumor cell line and normal adult plasma membrane preparations. Phosphatidic acid was identified as one of the 32P-labelled lipids in the tumor plasma membrane chloroform-methanol (2:1, v/v) extract. Phosphorylation of protein was not affected by cAMP or cGMP. However, calcium ion (in the presence or absence of calmodulin) significantly modifies the 32P labelling of a series of proteins in normal tissue but has little effect with the neoplastic preparations. Some plasma membrane proteins were capable of nucleotide binding, instead or in addition to being phosphorylated. Finally, the presence of membrane-bound phosphoprotein phosphatase(s) was also demonstrated in all the preparations examined by means of chase experiments with nonlabelled ATP or GTP, and (or) by the use of the phosphoprotein phosphatase inhibitor, orthovanadate.
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PMID:Endogenous hyperphosphorylation in plasma membrane from an ascites hepatocarcinoma cell line. 337 Jan 39

RNA from a rat liver tumor (Morris hepatoma 5123tc) was used to construct cDNAs together comprising the complete coding sequence of rat oncomodulin mRNA. Information obtained from these cDNAs as well as from primer extension analysis gave a deduced length for the complete oncomodulin mRNA of approximately 680 nucleotides (excluding the poly(A) tail) including a 5'-untranslated region of 97 +/- 2 nucleotides, a 324-nucleotide-coding sequence and a 259-nucleotide 3'-noncoding region. Comparison of the oncomodulin cDNA sequence with those coding for other members of the calcium-binding protein family shows little homology with the exception of a recently reported parvalbumin cDNA where the oncomodulin and parvalbumin nucleotide sequences are 59% identical in the protein-coding region. RNA blot analysis of poly(A+) RNA from normal adult rat liver gave no evidence of oncomodulin expression in this tissue. A single RNA species was detected, however, in RNA extracts from the hepatoma and from rat and human placentas. A probe prepared from one of the rat oncomodulin cDNAs hybridized with a single DNA species in restriction digests of hepatoma and normal DNA from rat and sequences in DNA of humans and other mammals. A 38-nucleotide sequence spanning the 5'-untranslated region and the first seven codons of the oncomodulin cDNA, was far less homologous than was the same region of a parvalbumin cDNA, to a chicken calmodulin cDNA sequence coding for the first calcium-binding domain. The oncomodulin gene appears to have diverged more from that of calmodulin than has the parvalbumin gene.
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PMID:A complete complementary DNA for the oncodevelopmental calcium-binding protein, oncomodulin. 355 95


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