Pyrimidine phosphorylase activity in differentiating HL-60 leukemia cells

Z. Zhu, J. A. Sokoloski, M. P. Liu, A. C. Sartorelli, R. E. Handschumacher

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously demonstrated that high concentrations of intracellular uridine (Urd) lead to induction of the differentiation of HL-60 cells, suggesting that Urd may have a role in cellular homcostasis. To gain information on the function of Urd in cellular maturation, the level of Urd phosphorylase activity, which appears to be responsible for the catabolism of intracellular Urd, was measured in HL-60 cells induced to differentiate along the granulocytic and monocytic pathways by a variety of chemical inducers. Undifferentiated HL-60 cells possessed relatively low Urd cleavage activity, which was inferred to be Urd phosphorylase because of its inhibition by benzylacyclouridine (BAU). Induction of differentiation by either dimethylsulfoxide (DMSO), 12 O-tetradecanoylphorbol-13-acetate (TPA), or 1.25-dihydroxyvitamin D3 (Vit D3) increased the catabolism of Urd by Urd phosphorylase three to 20-fold compared with undifferentiated cells. The increase in enzyme activity was dependent on the extent of differentiation. Thymidinc (Tdr) phosphorolysis activity was also markedly increased by the initiation of maturation by DMSO or TPA. These findings suggest that Urd or a metabolite thereof may be an important factor in regulating the differentiation of HL-60 cells.

Original languageEnglish (US)
Pages (from-to)263-274
Number of pages12
JournalMolecular and Cellular Differentiation
Volume4
Issue number3
StatePublished - Dec 1 1996

Keywords

  • HL-60 cells
  • differentiation
  • leukemia
  • pyrimidine phosphorylase
  • uridine

ASJC Scopus subject areas

  • Genetics
  • Cell Biology
  • Cancer Research

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