Growth inhibition and differentiation induction in murine erythroleukemia cells by 4-hydroxynonenal.
4-Hydroxynonenal (HNE) is one of the major end products of lipid peroxidation. Here we show that the exposure of murine erythroleukemia (MEL) cells to 1 microM HNE, for 10.5 h over 2 days, induces a differentiation comparable with that observed in cells exposed to DMSO for the whole experiment (7 days). The exposure of MEL cells for the same length of time demonstrates a higher degree of differentiation in HNE-treated than in DMSO-treated MEL cells. The protooncogene c-myc is down-modulated early, in HNE-induced MEL cells as well as in DMSO-treated cells. However, ornithine decarboxylase gene expression first increases and then decreases, during the lowering of the proliferation rate. These findings indicate that HNE, at a concentration physiologically found in many normal tissues and in the plasma, induces MEL cell differentiation by modulation of specific gene expression.
Rinaldi
M
M
Laboratory of Molecular Medicine & Biotechnology, University Campus Bio-Medico, School of Medicine, Roma, Italy.
Barrera
G
G
Spinsanti
P
P
Pizzimenti
S
S
Ciafrè
S A
SA
Parella
P
P
Farace
M G
MG
Signori
E
E
Dianzani
M U
MU
Fazio
V M
VM
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc; D006131:Growth Inhibitors / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D009955:Ornithine Decarboxylase / Q000235:genetics; D014407:Tumor Cells, Cultured
D000447:Aldehydes; D006131:Growth Inhibitors; D009955:Ornithine Decarboxylase; C027576:4-hydroxy-2-nonenal