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KMID : 0811719980020030369
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Korean Journal of Physiology & Pharmacology
1998 Volume.2 No. 3 p.369 ~ p.376
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Hydroxyl Radical-Mediated Commitment of HL-60 Cells to Differentiation: Modulation of Differentiation Process by Phosphodiesterase Inhibitors
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Young Jin Cho
Woong Shick Ahn/Seok Ho Cha/Kweon-Haeng Lee/Won Il Kim/Myung Hee Chung
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Abstract
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Ms report shows that hydroxyl radical, generated by a Fenton reaction involving adenosine 5'-diphosphate/Fe2+ complex (5-15 micrometer) and H2O2 (2 micrometer), induced differentiation of HL-60 cells in a dose- and time-dependent manner. This is evidenced by the increases in 12-O-tetradecanoylphorbol 13-acetate- and fMLP-stimulated superoxide production capability. The cells exposed to hydroxyl radical for defined periods (24~96 hr) continued to differentiate even after the hydroxyl radical generating system had been removed. The differentiated cells displayed fMLP-stimulated calcium mobilization and increased expression of myeloid-specific antigen CD11b and CD14. The extent of the differentiation was markedly reduced by desferrioxamine (100micrometer), dimethylthiourea (5 mM), N,N'-diphenyl-1,4-phenylenediamine (2 micrometer), and N-acetyl-L-cysteine (5 mM). The induction of differentiation by hydroxyl radical was enhanced by 3-isobutyl-1-methylxanthine (200 micrometer) and Ro-20-1724 (8 micrometer), and inhibited by dipyridamole (2 micrometer). These results suggest that hydroxyl radicals may induce commitment of HL-60 cells to differentiate into more mature cells of myelomonocytic lineage through specific signal-transduction pathway that is modulated by phosphodiesterase inhibitors.
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KEYWORD
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Differentiation, Hydroxyl Radical, Phosphodiesterase Inhibitors, Leukemia, Human,
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