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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/29399
Ver los metadatos del registro completo
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 Técnicas2025-09-29T09:33:53Zoai: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:34982025-09-29 09:33:53.985CONICET 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 |
_version_ |
1844613045044641792 |
score |
13.070432 |