Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Different CD15 murine monoclonal antibodies were studied. These antibodies appeared to react specifically with the human myeloid-lineage-derived cell types in both peripheral blood and bone marrow. The antigens recognized by these antibodies were immunoprecipitated from lysates of 125I-labelled neutrophilic PMNs of healthy donors and subsequently analysed by electrophoresis on SDS-polyacrylamide gel and autoradiography. All antibodies precipitated the same membrane polypeptides from the membrane-iodinated PMN lysates: 105 and 150-kDa as most prominent, together with 260-, 230-, 67- and 52-kDa polypeptides. Absorption studies were performed with synthesized carbohydrate molecules. Antibody B4.3 appears to be directed against 3-alpha-fucosyl-N-acetyl-lactosamine (FAL). Competition experiments with 125I-labelled B4.3 demonstrated complete inhibition of binding by B4.3 and three other CD15 antibodies (VIM D5, UJ308, MI/N1), and partial inhibition by three additional antibodies (FMC10, FMC12, FMC13), indicating binding to the same antigenic structure. None of the antibodies reacted with monocytes using the immunofluorescence technique, but after neuraminidase digestion of these cells, positive reactions were obtained with all antibodies. Immunoprecipitation with lysates of both native and neuraminidase-digested monocytes showed no polypeptide bands. Monocytic differentiation of the myeloid cell line HL60 by 12-O-tetradecanoylphorbol-13-acetate (TPA) was accompanied by a decrease in reactivity with the antibodies, which could be reversed by neuraminidase digestion. This indicates that 3-alpha-fucosyl-N-acetyl-lactosamine is masked for the detection with antibodies upon monocytic differentiation by sialylation. Human x mouse myeloid cell hybrids were obtained after fusion of human myeloid cells and the HPRT-deficient murine myeloid cell line WEHI-TG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of CD15 (FAL) on myeloid cells and chromosomal localization of the gene. 136 94

6-Thioguanine (6-TG)-induced differentiation of hypoxanthine phosphoribosyltransferase (IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8)-deficient HL-60 cells is characterized by 2 days of growth, after which morphological differentiation proceeds. Addition of the tRNA wobble base queuine, in the presence of 6-TG, maintains the proliferative capability of the cells. The ability of 6-TG to induce differentiation correlates with c-myc mRNA down-regulation, but queuine has no effect on this parameter. Treatment with 6-TG for 2-3 days commits HL-60 cells to granulocytic differentiation, and, once committed, these cells do not respond to the monocytic inducer phorbol 12-myristate 13-acetate. Nonetheless, when cells are treated with queuine and 6-TG, they maintain the promyelocytic morphology and are capable of being induced down the monocytic pathway by phorbol 12-myristate 13-acetate as indicated by stabilization of c-fms mRNA and cell adherence. In the absence of queuine, phorbol 12-myristate 13-acetate is incapable of inducing monocytic markers in the 6-TG-treated cells. The data presented indicate that 6-TG-induced differentiation of HL-60 cells is a tRNA-facilitated event and that the tRNA wobble base queuine is capable of maintaining both the proliferative and pluripotent potential of the cells.
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PMID:Queuine, a tRNA anticodon wobble base, maintains the proliferative and pluripotent potential of HL-60 cells in the presence of the differentiating agent 6-thioguanine. 198 36

The effects of cigarette smoke condensate (CSC) and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on gap junction structure, quantity and function were investigated. Gap junction morphology was studied in rotary-shadowed freeze-fracture replicas of primary chick embryo hepatocytes. CSC (24 micrograms/ml) induced a strong decrease of gap junction areas; within 6 h the areas were reduced by greater than 60%. In the first 3 h of exposure, TPA (100 ng/ml) also reduced gap junction areas, but in the next 3 h a partial recovery was observed. Protoplasmic fracture face centre-to-centre particle spacings were used as a measure for gap junction coupling. CSC had a slow (although not significant) reducing effect on particle spacings, while TPA induced a reduction from 10.6 nm (control) to 10.0 nm within 3 h, indicating a reduction of coupling. Gap junctions were quantified in thin sections of cultured chick embryo hepatocytes, V79 fibroblasts, and co-cultivated hepatocytes and V79 cells. CSC did not influence gap junction numbers in any of these cultures, while TPA treatment caused a disappearance of gap junctions between hepatocytes and between hepatocytes and V79 cells in the first 12 h of cultivation. In the following 36 h a slow recovery could be observed. Gap junctions between V79 cells had already disappeared within 30 min. Metabolic co-operation between hepatocytes and hypoxanthine-guanine phosphoribosyltransferase-deficient V79 cells was quickly and continuously blocked by CSC over 27 h, whereas the phorbol ester induced a transient block. The dissimilar effects of these compounds on both gap junction structure and function indicate that they act via different mechanisms. The finding that CSC did not inhibit phorbol ester protein kinase C binding and did not activate this protein kinase in vitro supports this hypothesis.
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PMID:Effects of cigarette smoke condensate and 12-O-tetradecanoylphorbol-13-acetate on gap junction structure and function in cultured cells. 211 59

Giardia lamblia, an aerotolerant anaerobe, respires in the presence of oxygen by a flavin, iron-sulfur protein-mediated electron transport system. Glucose appears to be the only sugar catabolized by the Embden-Meyerhof-Parnas and hexose monophosphate pathways, and energy is produced by substrate level phosphorylation. Substrates are incompletely oxidized to CO2, ethanol and acetate by nonsedimentable enzymes. The lack of incorporation of inosine, hypoxanthine, xanthine, formate or glycine into nucleotides indicates an absence of de novo purine synthesis. Only adenine, adenosine, guanine and guanosine are salvaged, and no interconversion of these purines was detected. Salvage of these purines and their nucleosides is accomplished by adenine phosphoribosyltransferase, adenosine hydrolase, guanosine phosphoribosyltransferase and guanine hydrolase. The absence of de novo pyrimidine synthesis was confirmed by the lack of incorporation of bicarbonate, orotate and aspartate into nucleotides, and by the lack of detectable levels of the enzymes of de novo pyrimidine synthesis. Salvage appears to be accomplished by the action of uracil phosphoribosyltransferase, uridine hydrolase, uridine phosphotransferase, cytidine deaminase, cytidine hydrolase, cytosine phosphoribosyltransferase and thymidine phosphotransferase. Nucleotides of uracil may be converted to nucleotides of cytosine by cytidine triphosphate synthetase, but thymidylate synthetase and dihydrofolate reductase activities were not detected. Uptake of pyrmidine nucleosides, and perhaps pyrimidines, appears to be accomplished by carrier-mediated transport, and the common site for uptake of uridine and cytidine is distinct from the site for thymidine. Thymine does not appear to be incorporated into nucleotide pools. Giardia trophozoites appear to rely on preformed lipids rather than synthesizing them de novo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemistry and metabolism of Giardia. 265 35

BALB/c mouse thymoma-derived T cell line, CAK4.4 (Thy-1+, L3T4-, Lyt-2-), produced a large amount of TCR-gamma mRNA, a trace amount of TCR-beta mRNA but no detectable level of TCR-alpha mRNA. Another BALB/c mouse thymoma-derived T cell line, CAK1.3 (Thy-1+, L3T4+, Lyt-2+), synthesized a high level of TCR-alpha as well as TCR-beta mRNA but did not produce any amount of TCR-gamma mRNA. HAT-sensitive clones were established from the two T cell lines. Azaguanine-resistant, HPRT- CAK4.4 cells and bromodeoxyuridine-resistant, TK- CAK1.3 cells were fused by electrofusion method and the resultant hybrids were analyzed for expression of TCR genes as well as the changes of their cell surface phenotypes. Transcription of TCR-gamma gene was completely suppressed in all hybrids tested, although Southern blot analysis showed that the hybrids maintained TCR-gamma chain genes derived from both parental cells. TCR-alpha gene transcription occurred normally in one hybrid. In two other hybrids, TCR-alpha gene transcription was strongly suppressed. Treatment of the hybrid cells with 12-O-tetradecanoyl phorbol-13-acetate reversed the suppression of TCR-alpha gene transcription, but TCR-gamma gene transcription was not recovered by the same treatment. However, transcription level of TCR-beta gene was not changed in all hybrids. Our results suggested that the different trans-acting regulatory mechanisms control the transcription levels of TCR-alpha and TCR-gamma genes and that such a transcriptional control may play a crucial role in the determination of orderly appearance of TCR-gamma and TCR-alpha gene products during T cell ontogeny in the thymus.
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PMID:Trans-acting regulatory factors for T cell antigen receptor alpha- and gamma-chain gene expression. 283 44

The aim of the study was to establish enzyme-deficient mutants of the human permanent cell line U-937. Following chemical mutagenesis with the use of ethyl methanesulfonate, this cell line was chronically exposed to increasing concentrations of the toxic hypoxanthine analogue 6-thioguanine. Cells surviving hypoxanthine-aminopterin-thymidine selective media were separated by glass adherence with the use of 12-O-tetradecanoyl-phorbol-13-acetate. Three mutant clones were established, which have remained hypoxanthine phosphoribosyltransferase (HPRT) deficient for a period of 7 months, as shown by indirect measurements with the use of autoradiography and scintillation counting of cells exposed to [3H]hypoxanthine. Since the phenotypic properties and growth behavior of U-937 cells have remained unaltered after the induced mutation, a highly restricted chromosomal segment coding for HPRT seems to have been mutated.
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PMID:Induction of hypoxanthine phosphoribosyltransferase deficiency in human U-937 cells. 345 59

Although a Chinese hamster V79 cell-based assay for inhibitors of metabolic cooperation is currently available, the development of a human cell-based assay is desirable in order to avoid inappropriate extrapolation from animal cells to human cells. Cells derived from a human teratocarcinoma cell line (designated PA-1), which has a stable pseudodiploid karyotype and excellent in vitro growth properties, were used in a metabolic cooperation assay. The assay was based on the metabolic isolation of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient variants in the presence of HGPRT-proficient cells and 6-thioguanine. Chemicals which inhibit the transfer of the lethal metabolite of 6-thioguanine from HGPRT-proficient to HGPRT-deficient cells will allow for recovery of the 6-thioguanine-resistant (HGPRT-deficient) cells. Chemicals tested included 12-O-tetradecanoylphorbol-13-acetate and related analogues phorbol-12,13-didecanoate, mezerein, and 4-phorbol-12,13-didecanoate. Concurring with results previously obtained in V79 cells, 12-O-tetradecanoylphorbol-13-acetate and phorbol-12,13-didecanoate strongly inhibited metabolic cooperation, whereas mezerein was moderately inhibitory and 4 alpha-phorbol-12,13-didecanoate was inactive. These cells thus hold promise as a human cell-based assay for inhibitors of metabolic cooperation.
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PMID:Characterization of a human teratocarcinoma cell assay for inhibitors of metabolic cooperation. 394

The antineoplastic agents marcellomycin (and related anthracycline antibiotics) and 6-thioguanine are effective inducers of the differentiation of cultured leukemia cells. Studies designed to investigate the relationship between structure and activity conducted with the anthracyclines in HL-60 human acute promyelocytic leukemia cells indicated a dissociation between cytotoxicity and maturation-inducing properties of these agents. In an analogous manner, 6-thioguanine induced effective erythroid and granulocytic differentiation of Friend and HL-60 leukemias, respectively, only in hypoxanthine-guanine phosphoribosyltransferase deficient cells. These findings suggest that 6-thioguanine need not be metabolized to a nucleotide to be active as an inducer of differentiation, and that the concentration of the 6-thiopurine required to initiate the commitment to maturation is greater than that producing cytotoxicity. Erythrodifferentiation of HGPRT negative Friend murine leukemia cells by 6-thioguanine was antagonized by tetracaine, d, 1-propranolol and 12-O-tetradecanoylphorbol-13-acetate, providing evidence for a cell membrane mediated component in the action of the purine antimetabolite. This suggests that the biochemical events that produce differentiation after exposure to 6-thioguanine may differ from those responsible for the toxic actions of the drug. Studies such as these, designed to gain an understanding of the target sites of inducers of differentiation, may lead to the development of new agents of potential therapeutic benefit in the treatment of certain forms of cancer based on the conversion of malignant cells to their non-proliferating mature counterparts.
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PMID:Induction of leukemia cell differentiation by chemotherapeutic agents. 640 65

We have studied the influence of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), the vitamin A derivative retinoic acid and the benzodiazepine diazepam on intercellular communication via established gap junctions in a monolayer of rat liver epithelial cells (RLB) at various times of incubation. Intercellular communication was measured as the transfer of [3H]hypoxanthine-derived nucleotides between RLB hypoxanthine guanine phosphoribosyl transferase+ (HPRT+) and RLB HPRT- cells. TPA only showed transient inhibition of metabolic cooperation: after 4 h of treatment, intercellular communication was reduced to about 40% of the control and longer treatments showed progressively less effect until 24 h of treatment, when no difference was seen between TPA-treated and control preparations. Retinoic acid was a more effective inhibitor: both 3 X 10(-6) M applied for 24 h and 10(-4) M applied for 6.5 h, caused a 50% inhibition of label transfer. The junctional communication could only be blocked at very high concentrations (5 X 10(-4) M) in short-exposure experiments, but this is possibly a consequence of non-specific effects on the cell membrane. When the incubation time was 24 h, a considerable portion of the gap junctions appeared to persist in the 'open' state. Diazepam showed no significant inhibitory effect in the experiments performed.
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PMID:Effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), retinoic acid and diazepam on intercellular communication in a monolayer of rat liver epithelial cells. 671 25

The influence of phorbol-related tumour promoters and non-promoters on metabolic cooperation between wild-type and mutant Chinese hamster cells has been studied. The recovery, in medium containing 8-azaguanine, of hypoxanthine phosphoribosyl transferase-deficient (HPRT-) V79 cells co-cultured with an excess (2 x 10(6) per 9 cm petri-dish) of wild-type cells was determined in the presence and absence of each compound. Under the latter conditions (solvent treatment only) metabolic cooperation consistently reduced the cloning efficiency of HPRT- cells to approximately 10% of that in cultures without wild-type cells. However, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), the most potent known tumour promoter, almost totally reversed the effect of wild-type cells on mutant recovery when included in the medium at concentrations as low as 1 nM. TPA also markedly enhanced the expression, in crowded cultures, of HPRT- mutants induced by the carcinogen N-methyl-N-nitrosourea. This property was not shared by other phorbol esters which are inactive as tumour promoters, or by polycyclic aromatic hydrocarbons, but was exhibited to a lesser degree by mezerein, a diterpene ester of significant but weaker promoting activity than TPA. Confirmation that the effect of TPA on mutant expression is the result of inhibition of metabolic cooperation was obtained in experiments using autoradiography, which showed that low doses are able to block the transfer of [3H]-uridine nucleotides from prelabelled V79 cells to unlabelled V79 cells in contact. These findings have prompted us to formulate a working hypothesis for the mode of action of TPA in vivo as a tumour promoter based on its interference with this type of intercellular communication.
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PMID:Inhibition of metabolic cooperation between mammalian cells in culture by tumor promoters. 727 9


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