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Oxidative stress is involved in hydroxyurea-induced erythroid differentiation
Tadashi Nagai1, Takahisa Tarumoto, Takuji Miyoshi
1Division 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
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.