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)

Acidification of endocytic vesicles has been implicated as a necessary step in various processes including receptor recycling, virus penetration, and the entry of diphtheria toxin into cells. However, there have been few accurate pH measurements in morphologically and biochemically defined endocytic compartments. In this paper, we show that prelysosomal endocytic vesicles in HepG2 human hepatoma cells have an internal pH of approximately 5.4. (We previously reported that similar vesicles in mouse fibroblasts have a pH of 5.0.) The pH values were obtained from the fluorescence excitation profile after internalization of fluorescein labeled asialo-orosomucoid (ASOR). To make fluorescence measurements against the high autofluorescence background, we developed digital image analysis methods for estimating the pH within individual endocytic vesicles or lysosomes. Ultrastructural localization with colloidal gold ASOR demonstrated that the pH measurements were made when ligand was in tubulovesicular structures lacking acid phosphatase activity. Biochemical studies with 125I-ASOR demonstrated that acidification precedes degradation by more than 30 min at 37 degrees C. At 23 degrees C ligand degradation ceases almost entirely, but endocytic vesicle acidification and receptor recycling continue. These results demonstrate that acidification of endocytic vesicles, which causes ligand dissociation, occurs without fusion of endocytic vesicles with lysosomes. Methylamine and monensin raise the pH of endocytic vesicles and cause a ligand-independent loss of receptors. The effects on endocytic vesicle pH are rapidly reversible upon removal of the perturbant, but the effects on cell surface receptors are slowly reversible with methylamine and essentially irreversible with monensin. This suggests that monensin can block receptor recycling at a highly sensitive step beyond the acidification of endocytic vesicles. Taken together with other direct and indirect estimates of endocytic vesicle pH, these studies indicate that endocytic vesicles in many cell types rapidly acidify below pH 5.5, a pH sufficiently acidic to allow receptor-ligand dissociation and the penetration of some toxin chains and enveloped virus nucleocapsids into the cytoplasm.
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PMID:Rapid acidification of endocytic vesicles containing asialoglycoprotein in cells of a human hepatoma line. 631 42

The advantage of using DNA content as a biochemical parameter because the results it gives are directly related to cellularity is discussed. As examples, comparisons of acid phosphatase and cathepsin D activities in rat liver and hepatoma and of acid phosphatase in human normal breast tissue and adenocarcinoma are considered. Contradictory results are obtained, depending whether they are related to DNA content, fresh tissue weight, or protein content.
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PMID:DNA and protein content as cellular biochemical parameters. A discussion with two examples: acid phosphatase and cathepsin D in rat liver and hepatoma and acid phosphatase in human breast normal tissue and adenocarcinoma. 673 49

Two procedures for quantitative determination of dolichol were studied and these were applied to analyze tissue and subcellular distribution. In the first procedure the dolichols were oxidized with Cr2O3 and reduced with NaB3H4. The radioactivity in the individual dolichols was measured using reversed-phase thin-layer chromatography. In the second procedure, dolichols were analyzed by high-pressure liquid chromatography. For determination of dolichyl phosphates the lipid extract was subjected to acid and alkaline hydrolysis, and after hydrolysis with acid phosphatase the distribution was determined by high-pressure liquid chromatography. Recovery was monitored by the addition of dolichol D15 and D23 phosphate to the homogenate. Rat spleen had the highest dolichol content (114 micrograms/g) followed by lower content in rat liver and brain. The distribution pattern was similar in all organs, with 18 and 19 isoprene residues as dominating components. Human organs contain considerably higher concentrations of dolichol, with the 19 and 20 isoprene residues as the main components. In rat liver, outer mitochondrial and Golgi membranes, lysosomes and plasma membranes contain considerable amounts of dolichol. A drastic increase in dolichol content was observed in rat liver hyperplastic nodules while human liver cirrhosis and hepatocarcinoma showed a marked decrease in dolichol. In the latter case, the distribution pattern was also changed. Of the total amount of dolichol present in the tissues, 2% was phosphorylated in human liver, 10% in human testis and 18% in rat liver. In rat liver mitochondria and in microsomes 4 and 31%, respectively, of the polyprenols were in activated form. The results demonstrated that dolichyl phosphate and dolichol concentrations were regulated by different mechanisms and that the two forms possessed an independent distribution.
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PMID:Separation, quantitation and distribution of dolichol and dolichyl phosphate in rat and human tissues. 684 49

The maximal activities of liver lysosomal enzymes (acid phosphatase and cathepsin D) were found to be increased in patients with chronic active hepatitis, cirrhosis and primary hepatocellular carcinoma. The ratio between maximal and basal activity (an expression of the degree of retention of the enzymes to lysosome) of acid phosphatase was significantly decreased in patients with chronic active hepatitis and cirrhosis whereas that of cathepsin D did not show any significant changes between normal and various liver disorders. Serum levels of both the enzymes were elevated significantly in patients with cirrhosis and primary hepatocellular carcinoma.
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PMID:Lysosomal enzyme activities in normals and in patients with chronic liver diseases. 688 25

Appreciable numbers of glycogenosomes were found in ascites hepatoma cells. They were lined by a single or sometimes double membranous structure exhibiting weakly positive acid phosphatase activity. Some were closely related to the Golgi apparatus, and a few showed wrapping of glycogen particles. The glycogen extracted from ascites hepatoma AH 13 cells was of two major types: a normal adult liver type, and a muscle type. Only the latter type gave the Cotton effect on measurement of the ORD and CD spectra. Small particulate, muscle type glycogen was observed in the glycogenosomes. Autophagy of normal adult liver type glycogen was never found. The engulfment of muscle type glycogen was accompanied by high acid and neutral alpha-glucosidase activity levels.
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PMID:Ultrastructural and biochemical studies of glycogenosome formation in ascites hepatoma AH 13 cells. 700 13

Heterogeneity of acid phosphatase in lysosomes of the rat's liver and the Zhaidel hepatoma was studied by the DEAE-cellulose chromatography. It is found that different substrates are hydrolyzed by different molecular forms of the enzyme. It is suggested that variability in the increase of the enzyme activities, measured with different substrates under alteration of lysosomes, may be due to the heterogeneity of molecular forms of acid phosphatase.
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PMID:[Acid phosphatase isoenzyme composition of the lysosomes of normal and tumor cells]. 708 Jan 95

A Golgi-rich fraction has been isolated from rat ascites hepatoma AH-130 cells. Unlike the usual procedure for isolating Golgi complexes from liver and other tissues, a hypotonic solution including 2 mM CaCl2 was used as the homogenization medium for the ascites hepatoma cells, followed by a combination of differential and discontinuous sucrose gradient centrifugations. Electron microscopic observation revealed that the isolated fraction consisted of cisternae, vesicles and tubular elements which were similar to those structures described previously for the Golgi fraction isolated from rat liver. Galactosyl- and sialyl-transferases were concentrated about 55- and 75-fold, respectively, in this fraction compared with the homogenate, indicating that these enzymes are useful markers for the Golgi complex of rat ascites hepatoma AH-130 cells, as they are for those of other normal tissues. The preparation was virtually free of cytochrome oxidase, but contained minor amounts of acid phosphatase, alkaline phosphatase and phosphodiesterase I activities. Electrophoretic analysis on sodium dodecylsulfate-polyacrylamide gels showed that the hepatoma Golgi membranes were resolved into at least 23 protein bands, which were apparently different from the electrophoretic profile of the plasma membrane isolated from the same hepatoma cells.
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PMID:Isolation and characterization of the Golgi complex from rat ascites hepatoma AH-130 cells. 714 13

Male inbred Fischer rats were fed a diet containing 5 p.p.m. aflatoxin for 1, 3, 4 1/2 and 6 weeks at which times groups were killed for histological and histochemical study. Aflatoxin produced a scattered individual cell necrosis of parenchymal cells by 1 week. At 3 weeks small basophilic proliferative foci were seen which increased in size and abundance to 6 weeks. These foci showed starvation-resistant glycogen, variable depletion of glucose-6-phosphatase, succinic dehydrogenase, aniline hydrogenase, membrane ATPase and acid phosphatase. At 6 weeks the foci showed the presence of gamma glutamyl transpeptidase and glucose-6-phosphate dehydrogenase. The basophilic foci were not preceded by other focal histological and histochemical change. The basophilic proliferative lesions are observed when an irreversible change has been induced in the liver. The role of such lesions in the histogenesis of hepatocellular carcinoma is discussed.
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PMID:Histochemical studies on the early proliferative lesion induced in the rat liver by aflatoxin. 724 Dec 69

In present study we studied the cytotoxic effects of beta-lapachone, a potent anticancer drug, on the human hepatoma cell line (HepA2) under serum-free condition. Most cells died after 2 microM beta-lapachone addition at 48 hours. No apoptotic characteristics of DNA ladder was documented by agarose DNA electrophoresis. The blockage of cell cycle at S phase and unscheduled DNA synthesis were demonstrated by flow cytometric analysis and anti-bromodeoxyuridine immunocytochemistry. Ultrastructural observation showed that the swollen mitochondria, dilatation and vesiculation of rER and proliferation of peroxisome-like granules appeared within the cytoplasm of HepA2 cells following drug treatment. Using enzyme cytochemistry, both peroxidase and acid phosphatase activities but not catalase activity were localised in these peroxisome-like granules. Therefore, these results suggested that (a) beta-lapachone has a novel cytotoxic effect on human hepatoma cell; (2) beta-lapachone induces the interruption of the cell cycle and unscheduled DNA synthesis in HepA2 cells; and (3) beta-lapachone promotes the proliferation of peroxisome-like granules containing peroxidase and acid phosphatase activities without evidence of catalase activity in hepatoma cell line.
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PMID:beta-Lapachone induced cell death in human hepatoma (HepA2) cells. 947 38

The expression of high- and low-molecular weight acid phosphatase (HMr- and LMr-AP) and zinc ion-dependent acid phosphatase (HMr-ZnAP and LMr-ZnAP) was compared in normal human liver and in Hep G2 human hepatocarcinoma cell line extracts. The investigation was carried out using Sephadex G-100 chromatography, molecular weight determination, and analysis of some distinctive biochemical characteristics and immunochemical properties. Normal human liver and Hep G2 cell lines expressed both HMr- and LMr-AP enzymes although in different proportions. HMr-ZnAP was detected only in human liver extract, while LMr-ZnAP was present only in hepatoma cell extract, indicating that they were differentially expressed in normal and transformed human liver cells.
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PMID:Acid phosphatase and zinc ion-dependent acid phosphatase expression in normal human liver and in Hep G2 (human hepatocellular carcinoma) cell line. 983 33


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