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Growth inhibition and differentiation induction in murine erythroleukemia cells by 4-hydroxynonenal
Authors:Monica Rinaldi  Giuseppina Barrera  Paola Spinsanti  Stefania Pizzimenti  Silvia Anna Ciafr    Paola Parella  Maria Giulia Farace  Emanuela Signori  Mario Umberto Dianzani  Vito Michele Fazio
Institution:  a Laboratory of Molecular Medicine & Biotechnology, University Campus Bio-Medico, School of Medicine, Roma, Italy b Institute of Experimental Medicine, CNR, Roma, Italy c Department of Experimental Medicine and Oncology, University of Torino, Torino, Italy d Department of Experimental Medicine and Biochemical Science, University of Roma “Tor Vergata”, Roma, Italy e Laboratory for Molecular Pathology and Gene Therapy, IRCCS H. Casa Sollievo della Sofferenza, Foggia, Italy
Abstract: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 μM 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.
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