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.

journal_name

Br J Haematol

authors

Nagai T,Tarumoto T,Miyoshi T,Ohmine K,Muroi K,Komatsu N,Sassa S,Ozawa K

doi

10.1046/j.1365-2141.2003.04309.x

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

657-61

issue

4

eissn

0007-1048

issn

1365-2141

pii

4309

journal_volume

121

pub_type

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