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Authordc.contributor.authorParis Pizarro, Irmgard es_CL
Authordc.contributor.authorMartínez Alvarado, P. es_CL
Authordc.contributor.authorCárdenas, S. es_CL
Authordc.contributor.authorPérez Pastene, C. es_CL
Authordc.contributor.authorGraumann, Rebecca es_CL
Authordc.contributor.authorFuentes, P. es_CL
Authordc.contributor.authorOlea Azar, Claudio es_CL
Authordc.contributor.authorCaviedes Fernández, Pablo es_CL
Authordc.contributor.authorSegura Aguilar, Juan 
Admission datedc.date.accessioned2010-06-08T13:12:21Z
Available datedc.date.available2010-06-08T13:12:21Z
Publication datedc.date.issued2005-03
Cita de ítemdc.identifier.citationCHEMICAL RESEARCH IN TOXICOLOGY 18 (3): 415-419en_US
Identifierdc.identifier.issn0893-228X
Identifierdc.identifier.urihttps://repositorio.uchile.cl/handle/2250/120969
Abstractdc.description.abstractWe report a new and specific mechanism for iron-mediated neurotoxicity using RCHT cells, which were derived from rat hypothalamus. RCHT cells exhibit immunofluorescent-positive markers for dopamine beta-hydroxylase and the norepinephrine transporter, NET. In the present study, we observed that iron-induced neurotoxicity in RCHT cells was dependent on (i) formation of an Fe-dopamine complex (100 mu M FeCl3:100 mu M dopamine); (ii) specific uptake of the Fe-dopamine complex into RCHT cells via NET (79 +/- 2 pmol Fe-59/mg/min; P < 0.05), since the uptake of the Fe-59-dopamine complex by the cells was inhibited by 30 mu M reboxetine, a specific NET inhibitor (78% inhibition, P < 0.001); and (iii) intracellular oxidation of dopamine present in the Fe-dopamine complex to aminochrome; (iv) inhibition of DT-diaphorase, since incubation of RCHT cells with 100 mu M Fe-dopamine complex in the presence of 100 mu M dicoumarol, an inhibitor of DT-diaphorase, induced significant cell death (51 +/- 5%; P < 0.061). However, this cell death was reduced by 75% when the cells were incubated in the presence of 30 mu M reboxetine (P < 0.01). No significant cell death was observed when the cells were incubated with 100 mu M dopamine, 100 mu M Fe-Dopamine complex, 100 mu M dicoumarol, or 100 mu M FeCl3 (8.3 +/- 2, 9 +/- 4, 8.5 +/- 3, or 9.7 +/- 2% of control, respectively). ESR studies using the spin trapping agent DMPO showed no formation of hydroxyl radicals when the cells were incubated with 100 mu M FeCl3 alone. However, using the same ESR technique, the formation of hydroxyl radicals and a carbon-centered radical was detected when the cells were incubated with 100 mu M Fe-dopamine complex in the presence of 100 mu M dicoumarol. These studies suggest that iron can induce cell toxicity by a mechanism that requires the formation and NET-mediated uptake of an Fe-dopamine complex, ultimately resulting in the intracellular formation of reactive species.en_US
Lenguagedc.language.isoenen_US
Publisherdc.publisherAMER CHEMICAL SOCen_US
Keywordsdc.subjectONE-ELECTRON REDUCTIONen_US
Títulodc.titleDopamine-dependent iron toxicity in cells derived from rat hypothalamusen_US
Document typedc.typeArtículo de revistaen_US


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