Inhibition of the differentiation of human myeloid cell lines by redox changes induced through glutathione depletion.
We have investigated the effect of redox changes in vivo on the differentiation of two human myeloid cell lines, HL-60 and KG-1. The glutathione-depleting agent diethyl maleate (DEM) prevented the development of differentiated features in response to phorbol esters, including adherence of the cells to plastic surfaces and repression of the myeloperoxidase and CD34 genes. Moreover, DEM abolished phorbol 12-myristate 13-acetate-induced activation of the transcription factors AP-1 and Egr-1, suggesting that inhibition of differentiation may be due, at least in part, to redox modifications of these proteins.
Esposito
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Dipartimento di Biochemica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Italy.
Agosti
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Morrone
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Morra
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Cuomo
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C
Russo
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Venuta
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Cimino
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D015703:Antigens, CD / Q000235:genetics; D018952:Antigens, CD34; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D051766:Early Growth Response Protein 1; D005978:Glutathione / Q000378:metabolism*; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins; D004915:Leukemia, Erythroblastic, Acute; D015473:Leukemia, Promyelocytic, Acute; D008298:Maleates / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000235:genetics; D010641:Phenotype; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018952:Antigens, CD34; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D008298:Maleates; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014157:Transcription Factors; D009195:Peroxidase; C014476:diethyl maleate; D005978:Glutathione; D013755:Tetradecanoylphorbol Acetate