Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages

Autores
Silva Souza, Hercules Antônio da; Lira, Maria Nathalia de; Costa Junior, Helio Miranda; Cruz, Cristiane Monteiro da; Silva Vasconcellos, Jorge Silvio; Nogueira Mendes, Anderson; Pimenta Reis, Gabriela; Alvarez, Cora Lilia; Faccioli, Lucia Helena; Serezani, Carlos Henrique; Schachter, Julieta; Muanis Persechini, Pedro
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
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
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
Fil: Costa Junior, Helio Miranda. Universidade Federal do Rio de Janeiro; Brasil
Fil: Cruz, Cristiane Monteiro da. Universidade Federal do Rio de Janeiro; Brasil
Fil: Silva Vasconcellos, Jorge Silvio. Universidade Federal do Rio de Janeiro; Brasil
Fil: Nogueira Mendes, Anderson. Universidade Federal do Rio de Janeiro; Brasil
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
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
Fil: Faccioli, Lucia Helena. Universidade de Sao Paulo; Brasil
Fil: Serezani, Carlos Henrique. Indiana University; Estados Unidos
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
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
Materia
5-Lipoxygenase Inhibitors
Atp
Cation Transporters
Macrophage
P2x7 Receptor
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/29399
Acceder
id CONICETDig_ad73446181b4c8eddb927ffe5e72dffc
oai_identifier_str oai:ri.conicet.gov.ar:11336/29399
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophagesSilva Souza, Hercules Antônio daLira, Maria Nathalia deCosta Junior, Helio MirandaCruz, Cristiane Monteiro daSilva Vasconcellos, Jorge SilvioNogueira Mendes, AndersonPimenta Reis, GabrielaAlvarez, Cora LiliaFaccioli, Lucia HelenaSerezani, Carlos HenriqueSchachter, JulietaMuanis Persechini, Pedro5-Lipoxygenase InhibitorsAtpCation TransportersMacrophageP2x7 Receptorhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1We 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.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; BrasilFil: 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; BrasilFil: Costa Junior, Helio Miranda. Universidade Federal do Rio de Janeiro; BrasilFil: Cruz, Cristiane Monteiro da. Universidade Federal do Rio de Janeiro; BrasilFil: Silva Vasconcellos, Jorge Silvio. Universidade Federal do Rio de Janeiro; BrasilFil: Nogueira Mendes, Anderson. Universidade Federal do Rio de Janeiro; BrasilFil: 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; BrasilFil: 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; ArgentinaFil: Faccioli, Lucia Helena. Universidade de Sao Paulo; BrasilFil: Serezani, Carlos Henrique. Indiana University; Estados UnidosFil: 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; BrasilFil: 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; BrasilElsevier Science2014-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/29399Silva 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; 1967-19770005-2736enginfo:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1016/j.bbamem.2014.04.006info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0005273614001412info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:01:54Zoai:ri.conicet.gov.ar:11336/29399instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:01:55.265CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages
title Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages
spellingShingle Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages
Silva Souza, Hercules Antônio da
5-Lipoxygenase Inhibitors
Atp
Cation Transporters
Macrophage
P2x7 Receptor
title_short Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages
title_full Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages
title_fullStr Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages
title_full_unstemmed Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages
title_sort Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages
dc.creator.none.fl_str_mv Silva Souza, Hercules Antônio da
Lira, Maria Nathalia de
Costa Junior, Helio Miranda
Cruz, Cristiane Monteiro da
Silva Vasconcellos, Jorge Silvio
Nogueira Mendes, Anderson
Pimenta Reis, Gabriela
Alvarez, Cora Lilia
Faccioli, Lucia Helena
Serezani, Carlos Henrique
Schachter, Julieta
Muanis Persechini, Pedro
author Silva Souza, Hercules Antônio da
author_facet Silva Souza, Hercules Antônio da
Lira, Maria Nathalia de
Costa Junior, Helio Miranda
Cruz, Cristiane Monteiro da
Silva Vasconcellos, Jorge Silvio
Nogueira Mendes, Anderson
Pimenta Reis, Gabriela
Alvarez, Cora Lilia
Faccioli, Lucia Helena
Serezani, Carlos Henrique
Schachter, Julieta
Muanis Persechini, Pedro
author_role author
author2 Lira, Maria Nathalia de
Costa Junior, Helio Miranda
Cruz, Cristiane Monteiro da
Silva Vasconcellos, Jorge Silvio
Nogueira Mendes, Anderson
Pimenta Reis, Gabriela
Alvarez, Cora Lilia
Faccioli, Lucia Helena
Serezani, Carlos Henrique
Schachter, Julieta
Muanis Persechini, Pedro
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv 5-Lipoxygenase Inhibitors
Atp
Cation Transporters
Macrophage
P2x7 Receptor
topic 5-Lipoxygenase Inhibitors
Atp
Cation Transporters
Macrophage
P2x7 Receptor
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
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
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
Fil: Costa Junior, Helio Miranda. Universidade Federal do Rio de Janeiro; Brasil
Fil: Cruz, Cristiane Monteiro da. Universidade Federal do Rio de Janeiro; Brasil
Fil: Silva Vasconcellos, Jorge Silvio. Universidade Federal do Rio de Janeiro; Brasil
Fil: Nogueira Mendes, Anderson. Universidade Federal do Rio de Janeiro; Brasil
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
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
Fil: Faccioli, Lucia Helena. Universidade de Sao Paulo; Brasil
Fil: Serezani, Carlos Henrique. Indiana University; Estados Unidos
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
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
description 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.
publishDate 2014
dc.date.none.fl_str_mv 2014-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/29399
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
0005-2736
url http://hdl.handle.net/11336/29399
identifier_str_mv 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
0005-2736
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1016/j.bbamem.2014.04.006
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0005273614001412
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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