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Oxidative stress is involved in hydroxyurea‐induced erythroid differentiation
Author(s) -
Nagai Tadashi,
Tarumoto Takahisa,
Miyoshi Takuji,
Ohmine Ken,
Muroi Kazuo,
Komatsu Norio,
Sassa Shigeru,
Ozawa Keiya
Publication year - 2003
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04309.x
Subject(s) - cellular differentiation , oxidative stress , cell culture , intracellular , biology , dna synthesis , microbiology and biotechnology , cell growth , chemistry , biochemistry , dna , gene , genetics
Summary. 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 β‐globin, δ‐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.