Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Plasma membranes from ascites hepatoma cells (AH-7974, AH-130) contained much smaller amounts of calmodulin (about half) and cyclic AMP phosphodiesterase (about one-third) compared to plasma membranes of rat livers. 2. Some of calmodulin molecules in liver plasma membranes were released by repeated washing. The 'washed' liver plasma membranes showed the presence of specific binding sites for externally added calmodulin molecules (bovine brain) (N = 140 pmol/mg protein, Kd = 7.9 . 10(-8) M). The calmodulin content of AH-7974 plasma membranes was not reduced by repeated washing. The binding of calmodulin to the 'washed' AH-7974 plasma membranes was only of nonspecific nature with negative cooperativity. 3. Plasma membranes (liver and AH-7974) appeared to contain both calmodulin-dependent and calmodulin-independent phosphodiesterase, but the stimulation by externally added Ca2+ plus calmodulin was rather small. Externally added calmodulin-dependent phosphodiesterase (bovine brain) was bound more to 'washed' liver plasma membranes than to 'washed' AH-7974 plasma membranes. Newly bound phosphodiesterase appeared to be more sensitive to the stimulation by Ca2+ plus calmodulin in 'washed' hepatoma plasma membranes than in 'washed' liver plasma membranes. 4. Preincubation of 'washed' plasma membranes (liver and hepatoma) with calmodulin did not affect the binding of phosphodiesterase, but the sensitivity of phosphodiesterase to the stimulation by Ca2+ plus calmodulin in hepatoma plasma membranes was lost.
 ...
PMID:Dynamics of calmodulin and cyclic AMP phosphodiesterase in plasma membranes of rat livers and ascites hepatomas. 627 Dec 50

Studies with a subcellular system demonstrated that the interaction of insulin with the adipocyte plasma membrane resulted in the generation from the plasma membrane of a mediator that activated mitochondrial pyruvate dehydrogenase (EC 1.2.4.1). The insulin-sensitive chemical mediator from the plasma membrane has been partially characterized. It has a molecular weight of 1000-1500. The chemical mediator has been extracted from skeletal muscle, adipocytes, hepatoma cells, and IM-9 lymphocytes. Insulin increased the amount or activity of the mediator in the first three cell types, whereas insulin decreased the activity or amount of the mediator in IM-9 lymphocytes. These insulin-induced variations were consistent with the biological responses of these cells to insulin treatment. The activities of insulin-sensitive enzymes, including pyruvate dehydrogenase, adipocyte low Km 3':5'-cyclic-AMP phosphodiesterase (EC 3.1.4.17), and adipocyte plasma membrane [Ca2+ + Mg2+]-ATPase were shown to be altered by the chemical mediator. The mediator may act by altering various protein kinases and phosphoprotein phosphatases that modulate the state of phosphorylation and activity of these enzyme systems. The existence of two mediators is proposed. The first may mediate dephosphorylation of various substrates, and the second may influence phosphorylation.
 ...
PMID:Chemical mediator or mediators of insulin action: response to insulin and mode of action. 628 77

3',5' Adenosine monophosphate (cAMP) inhibits the proliferation of Reuber H35 rat hepatoma cells at concentrations higher than 10(-5) M. This inhibitory effect can be demonstrated both in exponentially growing monolayer cultures and in single cell clonal growth. The inhibition of the cell proliferation is due to both a short term (division delay) and a long term effect (cytotoxicity). The short term effect seems to be due to cAMP itself as it is potentiated by the phosphodiesterase inhibitor 1-methyl,3-isobutyl xanthine (MIX). The long term effect probably is due to degradation products of the cyclic nucleotide. It is shown by a combination of time lapse cinematography, autoradiography, and flow cytofluorometry that the division delay is due to a prolongation of the S phase with no apparent changes in the duration of the G1 phase. The possible causes of this prolongation of the S phase by cAMP are discussed.
 ...
PMID:The effects of 3',5' adenosine monophosphate on the proliferation of Reuber H35 rat hepatoma cells in vitro. 629 19

1. The activities of cyclic cytidine 3',5'-monophosphate (cCMP) phosphodiesterase in normal rat liver and host liver (bearing hepatoma 5123 t.c.(h)) were compared with those of three Morris hepatomas of varying growth rates. 2. The results show that the order of enzyme activity was as follows: normal liver = host liver greater than 7794A (slow growth rate) greater than 5123 t.c.(h) (intermediate growth rate) greater than 7800 (fast growth rate). 3. The enzyme had a pH optimal value of about 7.0 and an apparent Km for cCMP about 2.8 mM; its activity was slightly affected by the presence of calmodulin (100 micrograms/ml) and/or CaCl2 (100 microM), but showed variable responses to other cations (La3+, Mg2+, Mn2+, Zn2+, Fe2+, Na+ and K+).
 ...
PMID:Decreased activities of cyclic cytidine 3',5'-monophosphate phosphodiesterase in Morris hepatomas having varying growth rates. 630 41

We have separated and characterized a Ca2+- and calmodulin-insensitive cyclic nucleotide phosphodiesterase from rat liver supernatant as well as an analogous enzyme from HTC hepatoma cells. Chromatography of rat liver supernatant on DEAE-cellulose in the presence and subsequently in the absence of 0.1 mM-CaCl2 resulted in the separation of two distinct phosphodiesterase activities, both of which preferentially hydrolysed cyclic GMP rather than cyclic AMP. One enzyme, E-Ib, was activated in the presence of Ca2+ and calmodulin, and the other, E-Ia, was not. The E-Ia enzyme, which did not bind to calmodulin-Sepharose, had Mr 325 000 and displayed anomalous kinetic behaviour [Km (cyclic GMP) 1.2 microM; Km (cyclic AMP) 15.4 microM]. The E-Ib enzyme, which bound to calmodulin-Sepharose in the presence of Ca2+, had Mr 150 000 and exhibited Michaelis-Menten kinetics for hydrolysis of cyclic GMP [Km (basal) 6.5 microM; Km (activated) 12.0 microM]. E-Ia activity was diminished by incubation with alpha-chymotrypsin and was unaffected by the action of a rat kidney lysosomal proteinase. Partial hydrolysis of E-Ib enzyme by alpha-chymotrypsin or the kidney proteinase resulted in irreversible activation of the enzyme. The E-I enzyme isolated from HTC hepatoma cells was similar to the rat liver E-Ia enzyme in many respects. Its apparent Mr was 325 000. Its activity was unaffected by calmodulin in the presence of Ca2+ or by incubation with the kidney proteinase, and was decreased by digestion with alpha-chymotrypsin. Unlike the liver E-Ia enzyme, however, the hepatoma enzyme exhibited normal kinetic behaviour, with Km (cyclic GMP) 3.2 microM. Although HTC cells contain two other phosphodiesterases analogous to those in rat liver and a calmodulin-like activator of phosphodiesterase, no calmodulin-sensitive phosphodiesterase was detected.
 ...
PMID:Ca2+-independent cyclic GMP phosphodiesterases from rat liver and HTC hepatoma cells. 631 Nov 63

Four main phosphodiesterase (PDE) forms were resolved and partially purified from rat liver and Morris hepatoma 5123tc(h). The activities of the high Km cyclic nucleotide PDE (form II) in hepatoma were markedly reduced compared to liver, while the activities of the low Km cAMP PDE (form III) and low Km cyclic nucleotide PDE (form IV) in hepatoma were markedly higher than those of liver. The partially purified low Km cAMP PDE's (forms III and IV) from liver showed non-linear Lineweaver-Burk plots, whereas the same enzyme forms in hepatoma displayed linear kinetics. Activation of low Km cGMP PDE activity by calmodulin was found with form I in liver whereas in hepatoma form II was responsive to calmodulin.
 ...
PMID:The isolation and characterization of cyclic nucleotide phosphodiesterases from Morris hepatoma 5123tc(h) and rat liver. 632 Dec 59

An insulin-sensitive subcellular system was developed from rat adipocytes consisting of plasma membranes and mitochondria. Direct addition of insulin, concanavalin A or anti-insulin receptor antibody to this system resulted in the production of a mediator substance from the plasma membrane that caused dephosphorylation of the alpha subunit of pyruvate dehydrogenase in the mitochondria with concomitant activation of the enzyme. The mediator activated pyruvate dehydrogenase by activating the pyruvate dehydrogenase phosphatase and not by inhibiting the pyruvate dehydrogenase kinase. This was similar to the mechanism by which insulin causes activation of the enzyme in the intact cell. The insulin-sensitive mediator material from the adipocyte plasma membrane was acid-stable with a molecular weight of 1,000 to 1,500. Our laboratory has shown that the mediator that activates pyruvate dehydrogenase was present in intact adipocytes, hepatoma cells, and IM-9 lymphocytes. Insulin altered the amount or activity of the mediator consistent with the effect of the hormone on the cell. Other laboratories have shown similar effects on skeletal muscle and liver. We have shown the mediator to mimic insulin action on the low Km cyclic adenosine monophosphate (AMP) phosphodiesterase and the (calcium++-magnesium++)-adenosine triphosphatase (Ca++-Mg++)-ATPase of adipocyte plasma membranes in addition to pyruvate dehydrogenase. Other laboratories have shown the mediator to activate glycogen synthase. A body of direct and indirect evidence exists that demonstrates that more than one mediator exists. The chemical nature of the mediator is unknown but probably represents a new family of intracellular mediators of hormone action. These mediators may have clinical relevance in postreceptor defects of obesity and type II diabetes (noninsulin-dependent diabetes mellitus).
 ...
PMID:The chemical mediators of insulin action: possible targets for postreceptor defects. 633 85

We have demonstrated the identity of calmodulin tightly bound to the particulate fractions of AH-66 hepatoma cells and normal liver with authentic soluble calmodulin and have compared the particulate calmodulin content of AH-66 cells with that of normal liver. Calmodulin bound to the particulate fractions of the hepatoma and normal liver cells was purified to electrophoretic homogeneity by a simple procedure which involves solubilization of the particulate fractions with LIS, extraction of the solubilized solution with 37.5% phenol, gel filtration, and affinity chromatography on Fluphenazine-Sepharose. There were no detectable differences between the particulate calmodulin thus purified and authentic soluble calmodulin of rat brain. The particulate calmodulin in the hepatoma and normal liver cells was assayed based on its ability to activate calmodulin-deficient phosphodiesterase after partial purification of calmodulin from the particulate fractions by solubilization with LIS and extraction with phenol as described above. In addition, the particulate calmodulin content in the hepatoma and normal liver cells was also measured after solubilization of the particulate fractions with Lubrol PX. The results obtained by these two different procedures indicate that calmodulin content in the particulate fraction as well as in the soluble fraction of the hepatoma is significantly higher than that in the corresponding fractions of normal liver.
 ...
PMID:A simple procedure for the purification of calmodulin bound to membranes; calmodulin bound to the particulate fraction of AH-66 hepatoma ascites cells. 684 26

Calmodulin contents of normal rat liver, host liver [bearing hepatoma 5123t.c.(h)], regenerating liver, and Morris hepatomas 7800, 5123t.c.(h), and 7794A were determined by phosphodiesterase assay and by radioimmunoassay. The calmodulin levels determined by both assays were significantly increased in three hepatomas when compared to the corresponding values of normal liver. The order of increase in calmodulin content was as follows: normal liver = host liver less than 7794A (slow growth rate) less than 5123t.c.(h) (intermediate growth rate) less than 7800 (fast growth rate). In regenerating liver (24 hr after partial hepatectomy), the calmodulin content was not different from that of normal liver. In good agreement with the literature, the calmodulin values measured by the phosphodiesterase assay were always lower than those determined by radioimmunoassay. Calcium and magnesium contents were measured by atomic absorption spectrophotometry in acid digests of these tissues. Both cation contents were significantly increased in the three hepatomas studied when compared to the corresponding values of normal liver; the extent of increase for calcium content (120 to 240%) was much greater than that for magnesium (30 to 40%). The order of increase for both cations was as follows: normal liver = host liver less than 5123t.c.(h) less than 7794A less than 7800. Therefore, there does not appear to be any correlation between the cation contents and hepatoma growth rates. In regenerating liver, magnesium content was about 14% higher than that of normal liver. In summary, the results indicate that only the increase of calmodulin appears to correlate positively with the growth rate of these tumors. This correlation suggests that calmodulin may be involved in tumor cell growth regulation.
 ...
PMID:Positive correlation between calmodulin content and hepatoma growth rates. 708 50

Low molecular weight RNAs were isolated from nuclei of the cellular slime mold Dictyostelium discoideum AX-3. Analysis of the RNAs by polyacrylamide gel electrophoresis showed that the vegetative cell nuclei contained, besides tRNA (Dd1), 5S RNA (Dd4), and 5.8S RNA (Dd7), at least 7 small RNA species (Dd3, Dd5, Dd6, Dd8, Dd9, Dd10, Dd11) of 4S to 8S as major components and that the 7 small RNAs were localized mainly in the nucleus and had no poyl(A) sequence. These nuclear RNA species were metabolically stable, as shown by a chase experiment. Dd6, Dd8, and Dd9 had similar gel electrophoretic mobilities to those of the small nuclear RNA species U1, U2, and U3, respectively, of rat liver. Analysis of the 5'-terminus of these RNA molecules with tobacco acid phosphodiesterase suggested that Dd6, Dd8, and Dd9 each contain a cap. Sequence analysis of the 3'-end labeled Dd9 RNA showed that the 3'-terminal region sequenced had sequence homology with that of rat Novikoff hepatoma U3 RNA. These results indicate that Dictyostelium nuclei contain a set of small nuclear RNA species which is structurally similar to that in mammalian cells. No qualitative differences were detected between the small nuclear RNA species of vegetative and early differentiating cells.
 ...
PMID:Isolation and characterization of small nuclear RNAs from Dictyostelium discoideum. 729 90


<< Previous 1 2 3 4 5 6 Next >>