title: Oxidative stress is involved in hydroxyurea-induced erythroid differentiation.
abstract: Hydroxyurea (HU), an inhibitor of DNA synthesis, can also induce haemoglobinization in certain erythroid cell lines. In this study, we report that intracellular peroxides levels were increased in HU-treated murine erythroleukaemia (MEL) cells and that l-acetyl-N-cysteine (LNAC), a potent reducing reagent, had a significant inhibitory effect on the HU-mediated induction of beta-globin, delta-aminolaevulinate synthase mRNA expression and haemoglobinization of MEL cells. In contrast, the addition of LNAC to dimethyl sulphoxide (DMSO)-treated MEL cells had a much smaller effect on the number of haemoglobinized cells. These findings suggest that oxidative stress is involved in HU-mediated induction of erythroid differentiation and that HU induces MEL cell differentiation by a mechanism different to that involved in DMSO-mediated differentiation. Our findings also suggest that the induction of MEL cell differentiation by HU does not involve RAS-MAP (mitogen-activated protein) kinase signalling.
authors.affiliation: Division of Haematology, and Division Cell Transplantation and Transfusion, Jichi Medical School, Kawachi-gun, Tochigi, Japan, and Laboratory of Biochemical Hematology, The Rockefeller University, New York, USA. t-nagai@jichi.ac.jp
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nagai
authors.forename: Takahisa
authors.initials: T
authors.lastname: Tarumoto
authors.forename: Takuji
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Ken
authors.initials: K
authors.lastname: Ohmine
authors.forename: Kazuo
authors.initials: K
authors.lastname: Muroi
authors.forename: Norio
authors.initials: N
authors.lastname: Komatsu
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sassa
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects; D005914:Globins / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D020014:K562 Cells; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology*; D010100:Oxygen / Q000502:physiology; D010545:Peroxides / Q000378:metabolism
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D010545:Peroxides; D005914:Globins; D020929:Mitogen-Activated Protein Kinase Kinases; D010100:Oxygen; D006918:Hydroxyurea