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Título

Influence of ornithine decarboxylase antizymes and antizyme inhibitors on agmatine uptake by mammalian cells

AutorRamos-Molina, Bruno; López-Contreras, Andrés J. CSIC ORCID; Lambertos, A.; Dardonville, Christophe CSIC ORCID ; Cremades, Asunción; Peñafiel, Rafael
Fecha de publicación2015
EditorSpringer Nature
CitaciónAmino Acids 47: 1025-1034 (2015)
ResumenAgmatine (4-aminobutylguanidine), a dicationic molecule at physiological pH, exerts relevant modulatory actions at many different molecular target sites in mammalian cells, having been suggested that the administration of this compound may have therapeutic interest. Several plasma membrane transporters have been implicated in agmatine uptake by mammalian cells. Here we report that in kidney-derived COS-7cell line, at physiological agmatine levels, the general polyamine transporter participates in the plasma membrane translocation of agmatine, with an apparent Km of 44 ± 7 μM and V <inf>max</inf> of 17.3 ± 3.3 nmol h<sup>-1</sup> mg<sup>-1</sup> protein, but that at elevated concentrations, agmatine can be also taken up by other transport systems. In the first case, the physiological polyamines (putrescine, spermidine and spermine), several diguanidines and bis(2-aminoimidazolines) and the polyamine transport inhibitor AMXT-1501 markedly decreased agmatine uptake. In cells transfected with any of the three ornithine decarboxylase antizymes (AZ1, AZ2 and AZ3), agmatine uptake was dramatically reduced. On the contrary, transfection with antizyme inhibitors (AZIN1 and AZIN2) markedly increased the transport of agmatine. Furthermore, whereas putrescine uptake was significantly decreased in cells transfected with ornithine decarboxylase (ODC), the accumulation of agmatine was stimulated, suggesting a trans-activating effect of intracellular putrescine on agmatine uptake. All these results indicate that ODC and its regulatory proteins (antizymes and antizyme inhibitors) may influence agmatine homeostasis in mammalian tissues.
Versión del editorhttp:/dx.doi.org/10.1007/s00726-015-1931-3
URIhttp://hdl.handle.net/10261/126358
DOI10.1007/s00726-015-1931-3
Identificadoresdoi: 10.1007/s00726-015-1931-3
issn: 0939-4451
e-issn: 1438-2199
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