Antioxidant N-acetyl-L-cysteine inhibits erythropoietin-induced differentiation of erythroid progenitors derived from mouse fetal liver.
To determine the role of reactive oxygen species in erythroid differentiation, we investigated the effects of an antioxidant, N-acetyl-L-cysteine (NAC), on the differentiation of erythroid progenitors derived from mouse fetal liver. In response to erythropoietin (Epo), erythroid progenitors undergo differentiation in vitro and express erythroid-specific genes such as betamajor-globin, Alas2, MafK, p45, Eklf, and Gata1. Expression of these genes was decreased in the presence of NAC, whereas the expression of c-myb, which is downregulated during erythroid differentiation, remained constant. Moreover, NAC treatment inhibited an increase in the number of cells expressing high levels of erythroid-specific antigen TER119. Treatment with another antioxidant, pyrrolidine dithiocarbamate, also caused the attenuation of TER119 expression. These results suggest that reactive oxygen species are involved in Epo-mediated erythroid differentiation.
Nagata
Makiko
M
Division of Developmental Biochemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.
Arimitsu
Nagisa
N
Ito
Takahiro
T
Sekimizu
Kazuhisa
K
D000111:Acetylcysteine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D001789:Blood Group Antigens / Q000032:analysis; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology; D004921:Erythropoietin / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D050982:GATA1 Transcription Factor / Q000032:analysis; D008099:Liver / Q000166:cytology* / Q000196:embryology* / Q000502:physiology; D050985:MafK Transcription Factor / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000943:Antigens, Differentiation; D001789:Blood Group Antigens; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D050985:MafK Transcription Factor; D017382:Reactive Oxygen Species; C489122:TER-119 antigen, mouse; D004921:Erythropoietin; D000111:Acetylcysteine