Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate Species

Detalhes bibliográficos
Autor(a) principal: Arezes, J.
Data de Publicação: 2013
Outros Autores: Costa, M., Vieira, I., Dias, V., Kong, X., Fernandes, R., Vos, M., Carlsson, A., Rikers, Y., Porto, G., Rangel, M., Hider, R., Pinto, J.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.16/1696
Resumo: Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI). NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.
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spelling Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate SpeciesIron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI). NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.This work is funded by FEDER funds through the Operational Competitiveness Programme – COMPETE, by national funds through FCT – Fundação para a Ciência e a Tecnologia under the projects FCOMP-01-0124-FEDER-015823(PTDC/SAU-MET/​113011/2009),FCOMP-01-0124-FEDER-007046(PTDC/BIA-BCM/​66818/2006)FCOMP-01-0124-FEDER-007506(PTDC/SAU-GMG/​67868/2006)and by the INOVA Foundation. JA, IV, MC and VD are recipients of FCT fellowships (www.fct.pt). JPP is supported by Programa Ciência (sponsored by POPH-QREN (4.2), with match-funding from the European Social Fund and Portuguese funds from the MCTES). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Public Library of ScienceRepositório Científico do Centro Hospitalar Universitário de Santo AntónioArezes, J.Costa, M.Vieira, I.Dias, V.Kong, X.Fernandes, R.Vos, M.Carlsson, A.Rikers, Y.Porto, G.Rangel, M.Hider, R.Pinto, J.2014-10-14T15:09:47Z20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/1696engArezes J, Costa M, Vieira I, Dias V, Kong XL, et al. (2013) Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate Species. PLoS ONE 8(11): e79870. doi:10.1371/journal.pone.00798701932-620310.1371/journal.pone.0079870info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-20T10:57:08Zoai:repositorio.chporto.pt:10400.16/1696Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:38:04.020114Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate Species
title Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate Species
spellingShingle Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate Species
Arezes, J.
title_short Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate Species
title_full Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate Species
title_fullStr Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate Species
title_full_unstemmed Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate Species
title_sort Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate Species
author Arezes, J.
author_facet Arezes, J.
Costa, M.
Vieira, I.
Dias, V.
Kong, X.
Fernandes, R.
Vos, M.
Carlsson, A.
Rikers, Y.
Porto, G.
Rangel, M.
Hider, R.
Pinto, J.
author_role author
author2 Costa, M.
Vieira, I.
Dias, V.
Kong, X.
Fernandes, R.
Vos, M.
Carlsson, A.
Rikers, Y.
Porto, G.
Rangel, M.
Hider, R.
Pinto, J.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Centro Hospitalar Universitário de Santo António
dc.contributor.author.fl_str_mv Arezes, J.
Costa, M.
Vieira, I.
Dias, V.
Kong, X.
Fernandes, R.
Vos, M.
Carlsson, A.
Rikers, Y.
Porto, G.
Rangel, M.
Hider, R.
Pinto, J.
description Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI). NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-01-01T00:00:00Z
2014-10-14T15:09:47Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.16/1696
url http://hdl.handle.net/10400.16/1696
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Arezes J, Costa M, Vieira I, Dias V, Kong XL, et al. (2013) Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate Species. PLoS ONE 8(11): e79870. doi:10.1371/journal.pone.0079870
1932-6203
10.1371/journal.pone.0079870
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publisher.none.fl_str_mv Public Library of Science
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