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)

Amino acid starvation causes an adaptive increase in the initial rate of transport of selected neutral amino acids in an established line of rat hepatoma cells in tissue culture. After a lag of 30 min, the initial rate of transport of alpha-aminoisobutyric acid (AIB) increases to a maximum after 4 to 6 h starvation of 2 to 3 times that seen in control cells. The increased rate of transport is accompanied by an increase in the Vmax and a modest decrease in the Km for this transport system, and is reversed by readdition of amino acids. The enhancement is specific for amino acids transported by the A or alanine-preferring system (AIB, glycine, proline); uptake of amino acids transported by the L or leucine-preferring system (threonine, phenylalanine, tyrosine, leucine) or the Ly+ system for dibasci amino acids (lysine) is decreased under these conditions. Amino acids which compete with AIB for transport also prevent the starvation-induced increase in AIB transport; amino acids which do not compete fail to prevent the enhancement. Paradoxically threonine, phenylalanine, tryptophan, and tyrosine, which do not compete with AIB for transport, block the enhancement of transport upon amino acid starvation. The starvation-induced enhancement of amino acid transport does not appear to be the result of a release from transinhibition. After 30 min of amino acid starvation, AIB transport is either unchanged or slightly decreased even though amino acid pools are already depleted. Furthermore, loading cells with high concentrations of a single amino acid following a period of amino acid starvation fails to prevent the enhancement of AIB transport, whereas incubation of the cells with the single amino acid for the entire duration of amino acid starvation prevents the enhancement; intracellular amino acid pools are similar under both conditions. The enhancement of amino acid transport requires concomitant RNA and protein synthesis, consistent with the view that the adaptive increase reflects an increased amount of a rate-limiting protein involved in the transport process. Dexamethasone, which dramatically inhibits AIB transport in cells incubated in amino acid-containing medium, both blocks the starvation-induced increase in AIB transport, and causes a time-dependent decrease in transport velocity in cells whose transport has previously been enhanced by starvation.
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PMID:Derepression of amino acid transport by amino acid starvation in rat hepatoma cells. 1 7

In certain lines of hepatoma tissue culture (HTC) cells, glutamine synthetase (EC 6.3.1.2) specific activity is increased 2.5- to 3-fold by the addition of glucocorticoids to the growth media. Actinomycin D blocks both the induction and deinduction of glutamine synthetase by glucocorticoids, suggesting a requirement of RNA synthesis for both processes. Using an antiserum raised against purified rat liver glutamine synthetase, we have precipitated radiolabeled glutamine synthetase from HTC cells. Electrophoresis of the immunoprecipitates on sodium didecyl sulfate-acrylamide gels isolates the subunit of glutamine synthetase and permits the radioactivity in the glutamine synthetase band to be quantitated. Using this technique, we have investigated the effect of dexamethasone, a synthetic glucocorticoid, on the rates of synthesis and degradation of glutamine synthetase. Dexamethasone (10(-7) M) increases the rate of synthesis of glutamine synthetase 2- to 3-fold but has no effect on the rate of glutamine synthetase degradation. The rates of total cell protein synthesis and degradation are not significantly affected by dexamethasone. The presence of actinomycin D at the time of removal of dexamethasone from induced cells prevents the fall in the induced rate of synthesis of glutamine synthetase normally seen when the inhibitor is removed from the culture medium. The regulation of glutamine synthetase by dexamethasone has been compared to the regulation of another dexamethasone-inducible enzyme in HTC cells, tyrosine aminotransferase, and been found to be similar in all parameters studied.
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PMID:Regulation of glutamine synthetase by dexamethasone in hepatoma tissue culture cells. 2 25

Dexamethasone, a synthetic glucocorticoid, selectively increased the rate of synthesis of mouse mammary tumor virus (MTV) RNA in clonal isolates of chronically infected rat hepatoma tissue culture cells. This hormonal effect occurred extremely rapidly and appeared to be mediated directly by the glucocorticoid-specific receptor protein. In addition to the viral RNA, unintegrated MTV DNA was also detected in these cells. Several lines of evidence are consistent with the idea that the unintegrated viral DNA is synthesized by reverse transcription of MTV RNA. (i) Unintegrated viral DNA accumulated only in the presence of dexamethasone and was produced with a time course that closely paralleled the increased accumulation of viral RNA. (ii) Density labeling of the viral DNA revealed that both strands were newly synthesized, implying a non-semiconservative mode of replication. (iii) Inhibitors of viral RNA synthesis prevented the appearance of unintegrated viral DNA. These data suggest that the production of unintegrated MTV DNA after dexamethasone treatment occurs as a secondary consequence of the hormonal induction of synthesis of viral RNA. In contrast to infected rat hepatoma cells, no unintegrated MTV DNA was detected in mouse mammary tumor cells or mouse lymphoma cells, despite the presence of high levels of viral RNA.
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PMID:Production of unintegrated mouse mammary tumor virus DNA in infected rat hepatoma cells is a secondary action of dexamethasone. 20 32

Glucocorticoids affect the composition and function of the plasma membrane in a variety of cell types. Cultured rat hepatoma (HTC) cells in tissue culture provide an excellent model system for analysis of such effects. In these cells, dexamethasone rapidly and dramatically inhibits the influx of amino acids sharing the A or alanine-preferring transport system. Inhibition is half-maximal within 2 h, and maximal after 6 h incubation with the hormone. The inhibition is rapidly reversed by insulin, and more slowly by removing the steroid. Microtubules and microfilaments are not apparently involved in this hormonal effect, but continuous protein synthesis is required for the glucocorticoid inhibition of transport. Dexamethasone also decreases the number of microvilli on the surface of HTC cells, increases their adhesiveness to a substratum, and dramatically decreases the production of plasminogen activator, but it does not affect the growth rate or plating efficiency of the cells. Variant cell lines stably resistant to dexamethasone inhibition of plasminogen activator production have been isolated using an agar-fibrin overlay technique to detect protease production by individual colonies of HTC cells. The hormonal resistance to inhibition of protease production is associated witha maintenance of inducibility of other glucocorticoid-regulated functions and therefore is not apparently secondary to abnormal or absent glucocorticoid receptor, but due to a lesion in a later step in hormone action specific for plasminogen activator. Combined genetic and biochemical analysis of such dexamethasone-resistant variants should facilitate study of the hormonal regulation of specific membrane phenotypes and of the role of proteases in this regulation.
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PMID:Glucocorticoids and the plasma membrane. 38 92

Freeze-fracture and thin-section methods were used to study tight junction formation between confluent H4-II-E hepatoma cells that were plated in monolayer culture in media with and without dexamethasone, a synthetic glucocorticoid. Three presumptive stages in the genesis of tight junctions were suggested by these studies: 1) "formation zones" (smooth P-fracture face ridges deficient in intramembranous particles), apparently matched across a partially reduced extracellular space, develop between adjacent cells; 2) linear strands and aggregates of 9--11 nm particles collect along the ridges of the formation zones. The extracellular space was always reduced when these structures were found matched with pits in gentle E-face depressions; 3) the linear arrays of particles on the ridges associate within the membranes to form the fibrils characteristic of mature tight junctions. The formation zones resemble tight junctions in terms of size, complexity and the patterns of membrane ridges. Although some of the beaded particle specializations may actually be gap junctions, it is unlikely that all can be interpreted in this way. No other membrane structures were detected that could represent developmental stages of tight junctions. Dexamethasone (at 2 x 10(-6)M) apparently stimulated formation of tight junctions. Treated cultures had a greater number of formation zones and mature tight junctions, although no differences in qualitative features of the junctions were noted.
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PMID:Tight junction development between cultured hepatoma cells: possible stages in assembly and enhancement with dexamethasone. 43 93

The effects of agents which are known to be differentiation inducers on a human hepatoma cell line PLC/PRF/5 were investigated. Dexamethasone (DEX), sodium butyrate (SB) or dimethylsulfoxide (DMSO) were examined. They all reduced cell proliferation but differ from each other in effect on the secretion of alphafetoprotein (AFP) and hepatitis B surface antigen (HBsAg), changes in morphology and RNA transcription. SB changed the cell from polygonal into a fibroblast-like type and decreased AFP secretion. DMSO decreased the cell size and changed AFP secretion in the same manner as SB. DEX changed the cell into a larger size, as well as increased AFP secretion. HBsAg secretion and also HB virus DNA transcription was enhanced by 3 agents. AFP and myc gene transcriptions were reduced by SB but DMSO reduced only AFP. Albumin gene transcription was enhanced by SB and DEX. These results indicate that the decrease of PLC/PRF/5 proliferation is induced through different mechanisms by these 3 agents.
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PMID:Effect of dexamethasone, dimethylsulfoxide and sodium butyrate on a human hepatoma cell line PLC/PRF/5. 128 20

The aim of our study was to investigate the suitability of Fao cells, derived from the Reuber H35 rat hepatoma as a tool for studying regulation of drug-metabolizing enzymes and drug metabolism. Fao cells express P450 2B, 2E, 3A and GST pi and were used to study the effects different inducers on these enzymes. Ethanol considerably increased the amounts of P450 2E and, to a lesser extent, P450 2B and GST pi mRNA and protein. Dexamethasone decreased the amounts of P450 2B, 3A and GST pi mRNAs, but had no appreciable effect per se upon the protein concentration of these enzymes. However, it antagonized the induction of P450 2E, 2B and GST pi by ethanol, even at the protein level. RU 486 decreased P450 2B protein and P450 2E mRNA and protein levels without effecting P450 3A and GST pi expression. RU 486 did not antagonize the dexamethasone effects, suggesting that at least some of these effects are not mediated by the glucocorticoid receptor. These data indicate that these cells constitute a suitable tool for studying the regulation of drug-metabolizing enzyme expression and drug metabolism.
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PMID:Effects of ethanol, dexamethasone and RU 486 on expression of cytochromes P450 2B, 2E, 3A and glutathione transferase pi in a rat hepatoma cell line (Fao). 130 37

Experiments were carried out to investigate the uptake and accumulation of Zn in rat hepatoma HTC cells, as affected by interfering metals (Cd, Cu), metallothionein synthesis inhibiting compounds (Actinomycin D, cycloheximide) and metallothionein synthesis stimulating compounds (dexamethasone, dibu-cAMP). Cell viability was tested under all experimental conditions by the measurement of LDH leakage, K+ uptake and total cell protein. Determinations of Zn were performed by AAS (total Zn) or by gamma-ray spectrometry (65Zn). Metallothionein analysis was carried out by Cd-saturation tests. The results indicate that cellular responses in rat hepatoma HTC cells with respect to the uptake and accumulation of 65Zn are fully comparable with literature data existing for 65Zn accumulation in rat hepatocytes, under all experimental conditions applied. Cu2+ and dibutyryl-cAMP did not significantly affect rates of 65Zn accumulation. Cd2+, Actinomycin D and cycloheximide reduced 65Zn uptake, but dexamethasone additions resulted in increased 65Zn accumulation in the cells. Effects on 65Zn were shown both in cytosolic and in the membranes/organelles cell fractions. HPLC chromatography in control cells suggested that newly accumulated cytosolic 65Zn was predominantly MT-associated. Dexamethasone-induced 65Zn accumulation could not be related to elevated cellular MT levels, nor were the total cytosolic Zn levels significantly affected. Non-specific attenuations in MT levels (Actinomycin D, cycloheximide and dibu-cAMP) yielded linear relations between cytosolic 65Zn and MT levels, without any change in cytosolic Zn (AAS). Combined addition of Cd and dexamethasone yielded elevated MT levels, but severely reduced total cytosolic Zn and 65Zn concentrations. The results further indicate the non-Zn-specific nature of dexamethasone-action and suggest the relatively easy Zn-complexing and Zn-release of MT. The simultaneous determinations of total cytosolic zinc and cytosolic 65Zn levels showed that the application and sole measurement of radiotracers may yield only one-sided views of what is actually present or occurring in the cells.
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PMID:Effects of cadmium, copper and metallothionein synthesis inhibiting and stimulating compounds on zinc uptake and accumulation in rat hepatoma HTC cells. 133 Mar 37

Glucocorticoid hormones act in the nucleus of the cell to alter expression of specific genes and change cell metabolism. In liver, these hormones have been reported to increase mitochondrial respiratory activity, which is regulated by both nuclear and mitochondrial gene products. We examined the effects of the synthetic glucocorticoid, dexamethasone, on the expression of mitochondrially encoded genes in a rat hepatoma cell line, H-4-II-E cells. Dexamethasone treatment of these cells increased mitochondrial RNA (mtRNA) levels 3- to 4-fold without changing the amount of mitochondrial DNA mtRNA levels could increase by enhanced mitochondrial gene transcription, by decreased degradation, or by some combination of the two. To determine if messenger RNA (mRNA) stabilization contributed to the increase in mtRNA levels, we compared the decay rates of cytochrome b mRNA from dexamethasone-treated and control cells after inhibition of RNA synthesis; cytochrome b mRNA half-life was 80 min in both treatment conditions. The levels of incompletely processed RNA precursors for at least two mtRNAs increased 3-fold more and 24 h earlier than the mature mRNAs. These results suggested that dexamethasone treatment resulted in increased mtRNA transcription. In addition, we examined the incorporation of [3H]uridine into mtRNA. Dexamethasone treatment expanded the uridine triphosphate pools 1.6-fold in H-4-II-E cells and decreased uridine triphosphate specific activity 2.3-fold; correcting for this change in precursor pool specific activity demonstrated increased mtRNA synthesis in dexamethasone-treated cells. Changes in expression of nuclear-encoded proteins that regulate mitochondrial genome transcription are a possible mechanism by which dexamethasone can increase mtRNA levels in these cells.
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PMID:Dexamethasone treatment increases mitochondrial RNA synthesis in a rat hepatoma cell line. 137 Jul 90

Insulin stimulates transcription and cytoplasmic accumulation of a specific mRNA (termed p33), while inhibiting transcription and accumulation of phosphoenolpyruvate carboxykinase (PEPCK) mRNA in rat H4IIE (H4) hepatoma cells. The present work examines the role of protein synthesis in regulation of these genes by insulin and dexamethasone. Like insulin, cycloheximide and anisomycin, two protein synthesis inhibitors, induced p33 transcription and reduced PEPCK transcription. The combination of either protein synthesis inhibitor and insulin did not induce p33 transcription or inhibit PEPCK transcription beyond that observed with either protein synthesis inhibitor alone. Dexamethasone induced both p33 and PEPCK transcription. The combination of insulin and dexamethasone, or protein synthesis inhibitors and dexamethasone, abolished dexamethasone-induced PEPCK transcription. Thus, protein synthesis inhibitors regulate transcription of the p33 and the PEPCK genes in an insulin-like manner.
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PMID:Protein synthesis and insulin regulation of p33 and PEPCK gene expression. 163 18


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