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)

The properties of a protein kinase-substrate complex precipitated with Ca2+ from the cytosol of AH-66 hepatoma cells were characterized. The endogenous phosphorylation reaction of the complex was little affected by addition of histone, cyclic nucleotides, Ca2+-calmodulin, or Ca2+-phospholipid but was increased about two-fold by addition of casein. The complex contained several phosphate acceptor proteins with molecular weights ranging from 74,000 to 13,000 as analyzed by two-dimensional gel electrophoresis. These phosphate acceptor proteins were specifically concentrated in the complex. The protein kinase in the complex was purified by successive chromatography and proved to be casein kinase 2.
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PMID:Further characterization of a protein kinase-substrate complex precipitable with Ca2+ from the cytosol fraction of AH-66 hepatoma cells. 408 71

The cyclic nucleotide-independent protein kinase which is separated from poly(A) polymerase during its purification from nuclei of rat liver and Morris hepatoma 3924A was purified essentially to homogeneity. Liver nuclear poly(A) polymerase was dissociated from protein kinase by phosphocellulose column chromatography. In contrast, protein kinase copurified with the hepatoma poly(A) polymerase on the phosphocellulose column. Neither liver nor hepatoma kinase was stimulated by spermine or inhibited by heparin. These enzymes did not utilize GTP as phosphoryl donor, or histones or tyrosine-containing [Val5]-angiotensin II as phosphoryl acceptors. The apparent Km with respect to ATP was similar for the liver (4.7 microM) and hepatoma (11 microM) kinases, and the apparent Km with respect to casein was identical (0.6 microgram/microliter) for these enzymes. Both enzymes were capable of phosphorylating poly(A) polymerase and stimulating both tumor and liver poly(A) polymerase activity. However, in addition to their different chromatographic properties, the two kinases differed in molecular weight (liver, 37,000; hepatoma, 56,000), in their response to various divalent metal ions, and in their ability to phosphorylate hepatoma poly(A) polymerase (Km 7.9 and 30 microgram/microliter for liver and hepatoma enzymes, respectively). These latter characteristics distinguished the liver and hepatoma protein kinases from each other as well as from the previously described NI protein kinase.
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PMID:Purification and characterization of a nuclear protein kinase from rat liver and a hepatoma that is capable of activating poly(A) polymerase. 609 60

The activities of the three DNA-dependent RNA polymerases from a rapidly growing rat tumour, Morris hepatoma 3924A, and from rat liver were examined. The activity of RNA polymerase I was higher in the tumour than in the liver. The enhanced capacity for RNA synthesis was a result of a higher concentration of polymerase I in the tumour as well as of an activation of this enzyme in vivo. The possibility that the high specific activity of the hepatoma polymerase I resulted from phosphorylation was investigated. Two major cyclic-AMP-independent nuclear casein kinases (NI and NII) were identified; the activity of protein kinase NII in the tumour was ten times that in liver. Protein kinase NII was capable of activating and phosphorylating RNA polymerase I in vitro. This kinase could also stimulate RNA polymerase II activity, although to a lesser extent than RNA polymerase I. RNA polymerase III was not affected by protein kinase NII. Protein kinase NII was tightly associated with polymerase I and was found even in purified preparations of the polymerase. Antibodies against both RNA polymerase I and protein kinase NII were present in sera of patients with certain rheumatic autoimmune diseases. These results imply that RNA polymerase I and protein kinase NII are in close association in vivo as well as in vitro and that polymerase phosphorylation may regulate the rate of ribosomal RNA synthesis in the cell.
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PMID:Phosphorylation of RNA polymerases: specific association of protein kinase NII with RNA polymerase I. 613 1

Poly(adenylic acid)-containing rat liver polysomal messenger ribonucleoprotein particles (pmRNP) were isolated and found to contain protein kinase activity. The association of the enzyme(s) with the particles was confirmed by experiments showing that the protein kinase activity comigrated with the pmRNP on metrizamide gradients and bound to oligo-(dT)-cellulose columns only under conditions where the pmRNP bound. The following properties were determined for the pmRNP-associated kinase(s). Casein and phosvitin were preferred substrates over histone and protamine. The optimal MgCl2 and KCl concentrations were found to be 12.5 and 50 mM, respectively. MnCl2 and CaCl2 could not replace MgCl2 and were inhibitory at low concentrations. The optimum pH range was 7.7--9.0, and the enzyme activity was cAMP independent. A molecular weight of 55 000--60 000 was determined for the kinase(s) by sucrose gradient analysis. The enzyme(s) was capable of phosphorylating proteins endogenous to the pmRNP. Membrane-bound pmRNP contained much less kinase activity than free pmRNP while pmRNP from hepatoma 7777 contained an elevated level of the enzyme(s). The relationship between the protein kinase activity and one of the pmRNP proteins of molecular weight 66 000 is discussed.
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PMID:Characterization of protein kinase activity associated with rat liver polysomal messenger ribonucleoprotein particles. 625 May 53

A cyclic nucleotide-independent, polyamine-responsive protein kinase from the cytosol of Morris hepatoma 3924A, which phosphorylated heat-stable endogenous substrates and casein in the presence of polyamines (Criss, W.E., Yamamoto, M., Takai, Y., Nishizuka, Y. and Morris, H.P. (1978) Cancer Res. 38, 3540-3545) was observed to be stimulated by an endogenous protein activator. This protein activator was identified to be calmodulin. the polyamine-responsive protein kinase was also stimulated by purified calmodulin, but only in the presence of polyamines such as polylysine. This action of calmodulin did not require Ca2+ for activation of the enzyme; and activation occurred in the presence of EGTA. DNA and RNA inhibited the polyamine-responsive protein kinase, either in the presence or absence of Ca2+. Purified calmodulin, in the presence of cyclic AMP or cyclic GMP, did not activate the protein kinase. Therefore, polyamines such as polylysine are an absolute requirement for this expression of calmodulin action. The increased enzyme activity by calmodulin was accompanied with an increased Vmax and with no changes in the Km (ATP). High levels of cation, up to 100 mM Mg2+, did not effect the action of calmodulin. These results indicate that tumor cytosolic polyamine-responsive protein kinase is regulated by calmodulin, the latter being increased in the tumor tissue.
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PMID:Calmodulin stimulates polyamine-responsive protein kinase in the absence of Ca2+. 629 10

Endogenous phosphorylation reaction of the cytosol fraction of AH-66 hepatoma ascites cells in vitro was compared with that of normal rat liver. Cytosolic proteins with molecular weights of 125,000, 98,000, and 40,000 of AH-66 cells were heavily phosphorylated in a cyclic adenosine 3':5'-monophosphate-independent manner, but no counterpart was detected in normal liver cytosol. In order to examine whether these phosphoproteins were specifically present in AH-66 cytosol, cyclic adenosine 3':5'-monophosphate-independent protein kinases which phosphorylate these phosphoproteins were partially purified from AH-66 and liver cytosol by successive chromatography. Both kinase preparations were essentially free of endogenous protein substrates and catalyzed the phosphorylation of exogenous substrates, such as casein and phosvitin, but not histone and protamine. Both kinases markedly catalyzed the phosphorylation of the Mr 125,000, 98,000, and 40,000 proteins in AH-66 cytosol. The Mr 125,000, 98,000 and 40,000 proteins in liver cytosol were less intensely phosphorylated by the addition of the kinase from AH-66 cytosol. From these results, we conclude that these phosphoproteins are present in both AH-66 cytosol and liver cytosol but are highly concentrated in AH-66 cytosol.
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PMID:Characterization of protein phosphorylation of the cytosol of AH-66 hepatoma ascites cells. 630 94

Cortisol 21-mesylate, an alkylating derivatives of cortisol, was previously shown to exert an anti-glucocorticoid action in rat hepatoma cell culture (Simons, Thompson and Johnson 1980). In this study the effect of cortisol 21-mesylate on milk protein synthesis induced in cultured mouse mammary gland by glucocorticoid, insulin, and prolactin was investigated. Addition of cortisol 21-mesylate at concentrations ranging from 10(-8) M to 10(-6) M produced no inhibition of casein synthesis that was induced by glucocorticoid, insulin and prolactin in mammary explants from midpregnant mice. On the other hand, cortisol 21-mesylate in combination with insulin and prolactin stimulated casein synthesis in cultured tissue. The potency of cortisol mesylate was about 1/10 to 1/30th of that of cortisol. Cortisol 21-mesylate, like cortisol, also augmented the accumulation of alpha-lactalbumin in midpregnant rat mammary tissue cultured in the presence of insulin and prolactin. A cell-free competition study of glucocorticoid receptors using cytoplasmic extracts from mouse mammary tissue showed that cortisol 21-mesylate competitively inhibited the binding of dexamethasone on glucocorticoid receptors. The apparent affinity of cortisol 21-mesylate for glucocorticoid receptors is about 1/10th of that of cortisol. These results indicate that cortisol 21-mesylate acts as a glucocorticoid but not as an antiglucocorticoid in the mammary gland.
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PMID:Cortisol 21-mesylate exerts glucocorticoid action on the induction of milk protein synthesis in cultured mammary gland. 635 80

A cDNA clone complementary to mRNA encoding the precursor (Mr = 165,000) to the rat liver mitochondrial matrix enzyme carbamyl phosphate synthetase I (Mr = 160,000) was employed to compare relative amounts of the messenger in adult and fetal liver and in Morris hepatoma 5123D and 3924A cells. Northern blot analysis gave a size estimate for the messenger of 6,500-6,700 nucleotides. Carbamyl phosphate synthetase mRNA levels in 15-day-old fetal liver were less than 10% of adult levels; 5123D cells expressed the messenger at levels about 2-fold higher than normal adult liver, but the messenger was undetectable in 3924A cells. Albumin mRNA was also expressed in the former but not in the latter. Maintaining rats for 5 days on a diet containing 60% casein augmented the relative amount of carbamyl phosphate synthetase mRNA by about 2-fold, while a protein-free diet resulted in reduced levels of the mRNA (about 50% compared to animals on a normal diet). Finally, the pattern of hybridization of carbamyl phosphate synthetase cDNA to HindIII-digested genomic DNA showed no differences between normal liver and its corresponding hepatoma; however, a HindIII site polymorphism was observed between Buffalo and ACI rats.
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PMID:Regulation and expression of carbamyl phosphate synthetase I mRNA in developing rat liver and Morris hepatoma 5123D. 654 17

To investigate the effect of 2% salicylamide and protein feeding levels on animal and tumor growth, male ACI rats were injected with Morris hepatoma #3924A (1 X 10(6) cells) 1 week following the conversion to diets containing 8% or 25% casein (+/- 2% salicylamide). The animals were sacrificed on day 19 after tumor transplantation. Tumor area and tumor weight were significantly higher in animals on the 25% versus the 8% casein diets. Reduction in body weight gain and protein efficiency ratio (PER) were observed in drug-treated and tumor-bearing animals. Total serum protein and liver protein were significantly reduced in all tumor-bearing animals when compared to non-tumor-bearing rats. Liver protein from animals with tumors was significantly higher among those fed salicylamide, in comparison with the tumor bearing non-drug-treated animals. Overall, these results show that the growth of Morris hepatoma #3924A in ACI rats is enhanced by increased dietary protein and is significantly reduced by a low-protein diet and/or a salicylamide dietary supplement.
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PMID:Effect of salicylamide on the growth of a Morris hepatoma in rats fed 8% and 25% casein diets. 667 54

The present study was designed to clarify molecular mechanisms underlying inhibitory effect of dexamethasone on leukocyte infiltration in the inflammatory site. For the assay of leukocyte infiltration, two or four blebs were made s.c. on the back of rats by injecting with 2% carboxymethyl cellulose solution containing a chemoattractant, casein. Leukocyte accumulation in the bleb was inhibited considerably by local application of dexamethasone at a concentration of 0.6 X 10(-6) M. Hydrocortisone mesylate, which was reported in the study with hepatoma tissue culture cells to be a long-acting antagonist against glucocorticoid in binding to the corticoid receptor, blocked the above leukocyte inhibitory effect of dexamethasone when applied simultaneously with dexamethasone. The leukocyte infiltration was unaffected by the application of hydrocortisone mesylate alone. Treatment with androstenedione, which was reported to be inactive in the hepatoma tissue culture cells, did not interfere with the inhibitory effect of dexamethasone at all. Actinomycin D, when applied simultaneously with dexamethasone, significantly suppressed the leukocyte-inhibitory effect of dexamethasone. In contrast with those observations, the inhibitory effect of dexamethasone was not affected at all in cases that actinomycin D and hydrocortisone mesylate, respectively, were applied after the administration of dexamethasone. These results indicate essential roles of glucocorticoid receptor and gene expression for the manifestation of the inhibitory effect of dexamethasone on leukocyte infiltration in the inflammatory site.
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PMID:Mechanisms of anti-inflammatory action of dexamethasone: blockade by hydrocortisone mesylate and actinomycin D of the inhibitory effect of dexamethasone on leukocyte infiltration in inflammatory sites. 670 40


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