Monoamine transporter inhibitors and norepinephrine reduce dopamine-dependent iron toxicity in cells derived from the substantia nigra
Author | dc.contributor.author | Paris Pizarro, Irmgard | es_CL |
Author | dc.contributor.author | Martínez Alvarado, Pedro | es_CL |
Author | dc.contributor.author | Pérez Pastene, Carolina | es_CL |
Author | dc.contributor.author | Vieira, Marcelo N.N. | es_CL |
Author | dc.contributor.author | Olea Azar, Claudio | es_CL |
Author | dc.contributor.author | Raisman Vozari, Rita | es_CL |
Author | dc.contributor.author | Cárdenas, Sergio | es_CL |
Author | dc.contributor.author | Graumann, Rebecca | es_CL |
Author | dc.contributor.author | Caviedes Fernández, Pablo | es_CL |
Author | dc.contributor.author | Segura Aguilar, Juan | |
Admission date | dc.date.accessioned | 2007-05-31T20:22:25Z | |
Available date | dc.date.available | 2007-05-31T20:22:25Z | |
Publication date | dc.date.issued | 2005-03 | |
Cita de ítem | dc.identifier.citation | JOURNAL OF NEUROCHEMISTRY | en |
Identifier | dc.identifier.issn | 0022-3042 | |
Identifier | dc.identifier.uri | https://repositorio.uchile.cl/handle/2250/127251 | |
Abstract | dc.description.abstract | The role of dopamine in iron uptake into catecholaminergic neurons, and dopamine oxidation to aminochrome and its one-electron reduction in iron-mediated neurotoxicity, was studied in RCSN-3 cells, which express both tyrosine hydroxylase and monoamine transporters. The mean +/- SD uptake of 100 muM (FeCl3)-Fe-59 in RCSN-3 cells was 25 +/- 4 pmol per min per mg, which increased to 28 +/- 8 pmol per min per mg when complexed with dopamine (Fe(III)-dopamine). This uptake was inhibited by 2 muM nomifensine (43% p < 0.05), 100 muM imipramine (62% p < 0.01), 30 muM reboxetine (71% p < 0.01) and 2 mM dopamine (84% p < 0.01). The uptake of Fe-59-dopamine complex was Na+, Cl- and temperature dependent. No toxic effects in RCSN-3 cells were observed when the cells were incubated with 100 muM FeCl3 alone or complexed with dopamine. However, 100 muM Fe(III)-dopamine in the presence of 100 muM dicoumarol, an inhibitor of DT-diaphorase, induced toxicity (44% cell death; p < 0.001), which was inhibited by 2 muM nomifensine, 30 muM reboxetine and 2 mM norepinephrine. The neuroprotective action of norepinephrine can be explained by (1) its ability to form complexes with Fe3+, (2) the uptake of Fe-norepinephrine complex via the norepinephrine transporter and (3) lack of toxicity of the Fe-norepinephrine complex even when DT-diaphorase is inhibited. These results support the proposed neuroprotective role of DT-diaphorase and norepinephrine. | en |
Lenguage | dc.language.iso | en | en |
Publisher | dc.publisher | BLACKWELL PUBLISHING LTD | en |
Keywords | dc.subject | DT-DIAPHORASE INHIBITOR | en |
Título | dc.title | Monoamine transporter inhibitors and norepinephrine reduce dopamine-dependent iron toxicity in cells derived from the substantia nigra | en |
Document type | dc.type | Artículo de revista |
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