Oxidative stress is involved in hydroxyurea-induced erythroid differentiation.
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.
Nagai
Tadashi
T
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
Tarumoto
Takahisa
T
Miyoshi
Takuji
T
Ohmine
Ken
K
Muroi
Kazuo
K
Komatsu
Norio
N
Sassa
Shigeru
S
Ozawa
Keiya
K
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
D019384:Nucleic Acid Synthesis Inhibitors; D010545:Peroxides; D005914:Globins; D020929:Mitogen-Activated Protein Kinase Kinases; D010100:Oxygen; D006918:Hydroxyurea