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dc.contributor.author
Silva Souza, Hercules Antônio da
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Lira, Maria Nathalia de
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Costa Junior, Helio Miranda
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Cruz, Cristiane Monteiro da
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Silva Vasconcellos, Jorge Silvio
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Nogueira Mendes, Anderson
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Pimenta Reis, Gabriela
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Alvarez, Cora Lilia
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Faccioli, Lucia Helena
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Serezani, Carlos Henrique
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Schachter, Julieta
dc.contributor.author
Muanis Persechini, Pedro
dc.date.available
2017-11-30T20:54:21Z
dc.date.issued
2014-04
dc.identifier.citation
Silva Souza, Hercules Antônio da; Lira, Maria Nathalia de; Costa Junior, Helio Miranda; Cruz, Cristiane Monteiro da; Silva Vasconcellos, Jorge Silvio; et al.; Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages; Elsevier Science; Biochimica et Biophysica Acta - Biomembranes; 1838; 7; 4-2014; 1967-1977
dc.identifier.issn
0005-2736
dc.identifier.uri
http://hdl.handle.net/11336/29399
dc.description.abstract
We have previously described that arachidonic acid (AA)-5-lipoxygenase (5-LO) metabolism inhibitors such as NDGA and MK886, inhibit cell death by apoptosis, but not by necrosis, induced by extracellular ATP (ATPe) binding to P2X7 receptors in macrophages. ATPe binding to P2X7 also induces large cationic and anionic organic molecules uptake in these cells, a process that involves at least two distinct transport mechanisms: one for cations and another for anions. Here we show that inhibitors of the AA-5-LO pathway do not inhibit P2X7 receptors, as judged by the maintenance of the ATPe-induced uptake of fluorescent anionic dyes. In addition, we describe two new transport phenomena induced by these inhibitors in macrophages: a cation-selective uptake of fluorescent dyes and the release of ATP. The cation uptake requires secreted ATPe, but, differently from the P2X7/ATPe-induced phenomena, it is also present in macrophages derived from mice deficient in the P2X7 gene. Inhibitors of phospholipase A2 and of the AA-cyclooxygenase pathway did not induce the cation uptake. The uptake of non-organic cations was investigated by measuring the free intracellular Ca(2+) concentration ([Ca(2+)]i) by Fura-2 fluorescence. NDGA, but not MK886, induced an increase in [Ca(2+)]i. Chelating Ca(2+) ions in the extracellular medium suppressed the intracellular Ca(2+) signal without interfering in the uptake of cationic dyes. We conclude that inhibitors of the AA-5-LO pathway do not block P2X7 receptors, trigger the release of ATP, and induce an ATP-dependent uptake of organic cations by a Ca(2+)- and P2X7-independent transport mechanism in macrophages.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
5-Lipoxygenase Inhibitors
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Atp
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Cation Transporters
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Macrophage
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P2x7 Receptor
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Biofísica
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-06-09T15:00:50Z
dc.journal.volume
1838
dc.journal.number
7
dc.journal.pagination
1967-1977
dc.journal.pais
Países Bajos
dc.journal.ciudad
Ámsterdam
dc.description.fil
Fil: Silva Souza, Hercules Antônio da. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia de Pesquisa Translacional em Saúde e ambiente da Região Amazônica; Brasil
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Fil: Lira, Maria Nathalia de. Pontificia Universidad Catolica Do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia de Pesquisa Translacional em Saúde e ambiente da Região Amazônica; Brasil
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Fil: Costa Junior, Helio Miranda. Universidade Federal do Rio de Janeiro; Brasil
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Fil: Cruz, Cristiane Monteiro da. Universidade Federal do Rio de Janeiro; Brasil
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Fil: Silva Vasconcellos, Jorge Silvio. Universidade Federal do Rio de Janeiro; Brasil
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Fil: Nogueira Mendes, Anderson. Universidade Federal do Rio de Janeiro; Brasil
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Fil: Pimenta Reis, Gabriela. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia de Pesquisa Translacional em Saúde e ambiente da Região Amazônica; Brasil
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Fil: Alvarez, Cora Lilia. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia de Pesquisa Translacional em Saúde e ambiente da Região Amazônica; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
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Fil: Faccioli, Lucia Helena. Universidade de Sao Paulo; Brasil
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Fil: Serezani, Carlos Henrique. Indiana University; Estados Unidos
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Fil: Schachter, Julieta. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia de Pesquisa Translacional em Saúde e ambiente da Região Amazônica; Brasil
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Fil: Muanis Persechini, Pedro. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia de Pesquisa Translacional em Saúde e ambiente da Região Amazônica; Brasil
dc.journal.title
Biochimica et Biophysica Acta - Biomembranes
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1016/j.bbamem.2014.04.006
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info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0005273614001412
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