Induction of the differentiation of HL-60 cells by phorbol 12-myristate 13-acetate activates a Na(+)-dependent uridine-transport system. Involvement of protein kinase C
| Autor: | Alan C. Sartorelli, Robert E. Handschumacher, John A. Sokoloski, Chee Wee Lee |
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| Jazyk: | angličtina |
| Rok vydání: | 1991 |
| Předmět: |
Biology
Biochemistry Cell Line chemistry.chemical_compound Alkaloids Leukemia Promyelocytic Acute medicine Humans Inosine Molecular Biology Uridine Protein kinase C Protein Kinase C Uridine transport Sodium Biological Transport Cell Differentiation Cell Biology Staurosporine Kinetics chemistry Phorbol Tetradecanoylphorbol Acetate Ribonucleosides Thymidine Nucleoside Uracil nucleotide medicine.drug Research Article |
| Popis: | The Na(+)-dependent transport and facilitated diffusion of uridine were measured after differentiation of HL-60 leukaemia cells along the monocytic pathway by phorbol 12-myristate 13-acetate (PMA). PMA (200 ng/ml) caused a marked increase in Na(+)-dependent uridine transport within 48 h of exposure that was attributable to an increase in transport affinity (apparent Km values of 1.15 +/- 0.22 and 44 +/- 4.4 microM for PMA-induced and uninduced cells respectively), with no change in Vmax. (0.15 +/- 0.02 and 0.13 +/- 0.01 pmol/s per microliter of cell water for PMA-induced and uninduced cells respectively). A corresponding rapid decrease in both the rate of facilitated diffusion and the formation of uracil nucleotides occurred in PMA-induced cells. As a consequence of these changes, intracellular pools of uridine 3-4-fold greater than those in the medium were generated. A similar increase in Na(+)-dependent transport of adenosine, inosine, guanosine, thymidine and cytidine (Km values of 1-4 microM) was observed. The effects of PMA on the activation of the Na(+)-dependent uridine transporter were inhibited by staurosporine, suggesting the involvement of protein kinase C. The findings indicate that a change in the balance of the cellular mechanisms employed for nucleoside transport occurs during the monocytic differentiation of HL-60 leukaemia cells. |
| Databáze: | OpenAIRE |
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