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Hydroxyl Radical-Mediated Commitment of HL-60 Cells to Differentiation: Modulation of Differentiation Process by Phosphodiesterase Inhibitors

Cho, Young-Jin   (Department of Pharmacology, Catholic University Medical CollegeUU0013933  ); Ahn, Woong-Shick   (Department of Obstetrics and Gynecology, Kangnam St. Mary's Hospital, Catholic University Medical CollegeUU0013933  ); Cha, Seok-Ho   (Department of Pharmacology, Catholic University Medical CollegeUU0013933  ); Lee, Kweon-Haeng   (Department of Pharmacology, Catholic University Medical CollegeUU0013933  ); Kim, Won-Il   (Department of Clinical Pathology, St. Mary's Hospital, Catholic University Medical CollegeUU0013933  ); Chung, Myung-Hee   (Department of Pharmacology, Seoul National University College of MedicineUU0000691  );
  • 초록

    This report shows that hydroxyl radical, generated by a Fenton reaction involving adenosine $5'-diphosphate/Fe^{2+}$ complex ( $5-15\;{\mu}M$ ) and $H_2O_2$ ( $2\;{\mu}M$ ), 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 ( $100\;{\mu}M$ ), dimethylthiourea (5 mM), N,N'-diphenyl-1,4-phenylenediamine ( $2\;{\mu}M$ ), and N-acetyl-L-cysteine (5 mM). The induction of differentiation by hydroxyl radical was enhanced by 3-isobutyl-1-methylxanthine ( $200\;{\mu}M$ ) and Ro-20-1724 ( $8\;{\mu}M$ ), and inhibited by dipyridamole (2 ${\mu}M$ ). 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.


  • 주제어

    Differentiation .   Hydroxyl Radical .   Phosphodiesterase Inhibitors .   Leukemia .   Human.  

 저자의 다른 논문

  • Cho, Young-Jin (5)

    1. 1995 "Effect of Biphenyl Dimethyl Dicarboxylate on Chemical-Induced Hepatotoxicity" 한국독성학회지 = The Korean journal of toxicology 11 (2): 181~185    
    2. 1997 "Distributional Patterns of Phospholipase C Isozymes in Heart and Brain of Spontaneously Hypertensive and Normotensive Rats" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 1 (4): 385~392    
    3. 1997 "Endothelin Increases Intracellular Free Calcium in Isolated Rat Nephron" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 1 (5): 565~572    
    4. 2005 "5-Hydroxytryptamine Inhibits Glutamatergic Synaptic Transmission in Rat Corticostriatal Brain Slice" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 9 (5): 255~262    
    5. 2006 "Fluoxetine Modulates Corticostriatal Synaptic Transmission through Postsynaptic Mechanism" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 10 (1): 31~38    
  • Ahn, Woong-Shick (3)

  • Cha, Seok-Ho (2)

  • Lee, Kweon-Haeng (8)

  • Chung, Myung-Hee (31)

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