Inhibition by pertussis toxin of the activation of Na+-dependent uridine transport in dimethyl-sulphoxide-induced HL-60 leukaemia cells

Sokoloski, John A.; Sartorelli, Alan C.; Handschumacher, Robert E.; Lee, Chee Wee

doi:10.1042/bj2800515

Cited by 15 publications

(9 citation statements)

References 32 publications

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“…First, in intact myeloid cells, inhibitory effects of PTX on "basal" activities have been repeatedly observed. Specifically, PTX reduces basal inositol phosphate production in human neutrophils and HL-60 cells (81,82), Na ϩ -dependent uridine uptake in HL-60 cells (83), and basal Na ϩ entry in rabbit neutrophils (84). It should also be mentioned that PTX can inhibit apparently agonist-independent long term events in HL-60 cells such as Me 2 SO-induced differentiation (85).…”

Section: High Constitutive Activity Of the Human Fpr: Implications Fomentioning

confidence: 99%

High Constitutive Activity of the Human Formyl Peptide Receptor

Wenzel-Seifert

Hurt

Seifert

1998

Journal of Biological Chemistry

103

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The formyl peptide receptor (FPR) couples to pertussis toxin (PTX)-sensitive G i -proteins to activate chemotaxis and exocytosis in neutrophils. PTX reduces not only formyl peptide-stimulated but also agonist-independent ("basal") G i -protein activity, suggesting that the FPR is constitutively active. We aimed at identifying an inverse FPR agonist, i.e. a compound that suppresses constitutive FPR activity. In Sf9 insect cell membranes, the G-protein heterotrimer

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Section: High Constitutive Activity Of the Human Fpr: Implications Fomentioning

confidence: 99%

High Constitutive Activity of the Human Formyl Peptide Receptor

Wenzel-Seifert

Hurt

Seifert

1998

Journal of Biological Chemistry

103

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“…Differentiation has also been observed in vivo in acute myelocytic leukemia patients receiving tiazofurin (51). There has been some suggestion for the involvement of a G-protein modulated signal transduction pathway in the neutrophilic differentiation of HL-60 cells (33). NB4 cells can be terminally differentiated to granulocytes with retinoic acid (29,47) and to monocytes with the combination of 12-O-tetradecanolyphorbol-13-acetate and 1,25-dihydroxyvitamin D 3 (52).…”

Section: Table I Initial Transport Rates For Nucleoside Transport In mentioning

confidence: 99%

“…Nucleoside transport processes appear to be regulated during cellular differentiation (21,33). HL-60 cells induced to differentiate to neutrophils by treatment with dimethyl sulfoxide (53), retinoic acid, or tiazofurin (an IMP dehydrogenase inhibitor) show a decrease in intracellular GTP and GDP pools (49,50,53) and an increase in the salvage of guanosine and guanine (50).…”

Section: Table I Initial Transport Rates For Nucleoside Transport In mentioning

confidence: 99%

“…Other cell lines such as L1210 murine leukemia cells and IEC-6 mouse intestinal epithelial cells, express multiple transporters, including equilibrative and concentrative transporters, simultaneously (18,15). As well, NT activities within the same cell type have been observed to change with changes in growth state (26,27), differentiation (21,(32)(33)(34)(35)(36)(37), and neoplastic transformation (28). For example, induction of monocytic (21,35) or neutrophilic differentiation (33,34) of HL-60 human leukemia cells leads to a decrease in es nucleoside transport activity and increased Na ϩ -dependent nucleoside transport activity (33)(34)(35).…”

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confidence: 99%

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Characterization of a Novel Na+-dependent, Guanosine-specific, Nitrobenzylthioinosine-sensitive Transporter in Acute Promyelocytic Leukemia Cells

Flanagan

Meckling‐Gill

1997

Journal of Biological Chemistry

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NB4 cells are the only bona fide in vitro model of human acute promyelocytic leukemia. We have examined cytidine and guanosine transport in this cell line and characterized a novel guanosine-specific transporter. Cytidine transport occurred predominately by equilibrative nitrobenzylthioinosine (NBMPR)-sensitive (es) transport. In the presence of Na ؉ , guanosine at various concentrations accumulated at least 6-fold above equilibrium. The initial rate of guanosine transport in Na ؉ buffer decreased by 75% with the addition of 1 M NBMPR and the IC 50 for NBMPR inhibition was 0.7 ؎ 0.1 nM. Replacement of Na ؉ with choline also resulted in a 75% decrease in total guanosine transport. The potent inhibition of guanosine transport by NBMPR and the loss of transport in choline suggested that a Na ؉ -dependent NBMPR-sensitive transporter was responsible for the majority of guanosine uptake. This concentrative, sensitive transporter is Na ؉ dependent with a stoichiometric coupling ratio of 1:1. This novel transporter, referred to as csg, is guanosine-specific with total guanosine transport inhibited by only 50% in the presence of 1 mM competing nucleosides. HL-60, acute myelocytic leukemia cells, do not exhibit csg activity while L1210, murine acute lymphocytic leukemia cells, exhibit csg transport. The presence of the csg transporter suggests an important role for guanosine in particular forms of leukemia and may provide a new target for cytotoxic therapy.Purine and pyrimidine nucleotides, and their related metabolic products, participate in numerous biological processes.

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“…4, 7-9) Lee and co-workers indicated that both equilibrative and Na + -dependent nucleoside transport systems are expressed in undifferentiated HL60 cells, but only low levels of Na + -dependent uridine transport exist in the cells. [10][11][12] On the other hand, human monocytes/macrophages have been reported to possess equilibrative nucleoside transporters. 4,5) However, the expression of Na +dependent nucleoside transport systems in such cells is controversial.…”

Section: Introductionmentioning

confidence: 99%

Possibility of Contribution of Nucleoside Transport Systems to Pirarubicin Uptake by HL60 Cells but Not Mononuclear Cells

Nagasawa

Ohnishi

Yokoyama

1998

Japanese Journal of Cancer Research

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Previously, we reported that pirarubicin (THP), an anthracycline, was taken up, at least in part, by both human leukemic HL60 cells and mononuclear cells (MNCs) via a carrier-mediated system. In this study, the possibility of a contribution of nucleoside transport systems to the uptake of THP by HL60 cells and MNCs was investigated. The experiments were performed after both types of cells had been pretreated with a metabolic inhibitor, 2, 4-dinitrophenol, to deplete cellular ATP. In HL60 cells, THP uptake was increased and decreased significantly by treatment with equilibrative nucleoside transport inhibitors, nitrobenzylthioinosine (NBMPR), nitrobenzylthioguanosine and dilazep, in the presence and absence, respectively, of an inwardly directed Na + + + + -gradient. THP uptake by HL60 cells showed an overshoot in the presence of the gradient, and was decreased by treatment of the cells with monensin, indicating that the uptake partially depended on the Na + + + + -gradient. In HL60 cells in which equilibrative nucleoside transport was inhibited by NBMPR, THP uptake in the presence of the gradient was inhibited by Na + + + + -dependent concentrative nucleoside transport inhibitors, but no inhibition was observed in the absence of the gradient. In MNCs, conversely, there was no effect of any equilibrative nucleoside transport inhibitor or the Na + + + + -gradient on THP uptake. These results suggested that THP was taken up, at least in part, via both equilibrative and concentrative nucleoside transport systems in HL60 cells, but not in MNCs. Key words:Pirarubicin -Uptake mechanism -Nucleoside transport system -Human leukemia HL60 cell -Human mononuclear cellWe have been studying the transport mechanisms for anthracyclines in human leukemia HL60 cells and human mononuclear cells (MNCs), as models of tumor and normal cells, respectively, in order to establish a strategy for selectively delivering anthracyclines to leukemia cells based upon the differences in their transport mechanisms. In our previous studies, it was indicated that pirarubicin (THP) was taken up by HL60 cells and MNCs via a carrier-mediated transport system(s), although what kinds of transporters are involved, and whether or not the system is common to the two types of cells, remained unclear.

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Inhibition by pertussis toxin of the activation of Na+-dependent uridine transport in dimethyl-sulphoxide-induced HL-60 leukaemia cells

Cited by 15 publications

References 32 publications

High Constitutive Activity of the Human Formyl Peptide Receptor

High Constitutive Activity of the Human Formyl Peptide Receptor

Characterization of a Novel Na+-dependent, Guanosine-specific, Nitrobenzylthioinosine-sensitive Transporter in Acute Promyelocytic Leukemia Cells

Possibility of Contribution of Nucleoside Transport Systems to Pirarubicin Uptake by HL60 Cells but Not Mononuclear Cells

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