Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO Ligands

Autores
Marginedas-Freixa, Irene; Alvarez, Cora Lilia; Moras, Martina; Hattab, Claude; Bouyer, Guillaume; Chene, Arnaud; Lefevre, Sophie D.; Le Van Kim, Caroline; Bihel, Frederic; Schwarzbaum, Pablo Julio; Ostuni, Mariano
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Two main isoforms of the Translocator Protein (TSPO) have been identified. TSPO1 isubiquitous and is mainly present at the outer mitochondrial membrane of most eukaryotic cells,whereas, TSPO2 is specific to the erythroid lineage, located at the plasma membrane, the nucleus,and the endoplasmic reticulum. The design of specific tools is necessary to determine the molecularassociations and functions of TSPO, which remain controversial nowadays. We recently demonstratedthat TSPO2 is involved in a supramolecular complex of the erythrocyte membrane, where micromolardoses of the classical TSPO ligands induce ATP release and zinc protoporphyrin (ZnPPIX) transport.In this work, three newly-designed ligands (NCS1016, NCS1018, and NCS1026) were assessed fortheir ability to modulate the functions of various erythrocyte?s and compare them to the TSPOclassical ligands. The three new ligands were effective in reducing intraerythrocytic Plasmodiumgrowth, without compromising erythrocyte survival. While NCS1016 and NCS1018 were the mosteffective ligands in delaying sorbitol-induced hemolysis, NCS1016 induced the highest uptake ofZnPPIX and NCS1026 was the only ligand inhibiting the cholesterol uptake. Differential effects ofligands are probably due, not only, to ligand features, but also to the dynamic interaction of TSPOwith various partners at the cell membrane. Further studies are necessary to fully understand themechanisms of the TSPO's complex activation.
Fil: Marginedas-Freixa, Irene. Institut National de la Transfusion Sanguine; . Université Paris Diderot - Paris 7; Francia. Université de la Réunion; Francia. Université des Antilles; Francia
Fil: Alvarez, Cora Lilia. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; Argentina
Fil: Moras, Martina. Université des Antilles; Francia. Institut National de la Transfusion Sanguine; . Université de la Réunion; Francia. Université Paris Diderot - Paris 7; Francia
Fil: Hattab, Claude. Université de la Réunion; Francia. Université Paris Diderot - Paris 7; Francia. Université des Antilles; Francia. Institut National de la Transfusion Sanguine;
Fil: Bouyer, Guillaume. Sorbonne Université; Francia
Fil: Chene, Arnaud. Université de la Réunion; Francia. Université des Antilles; Francia. Institut National de la Transfusion Sanguine; . Université Paris Diderot - Paris 7; Francia
Fil: Lefevre, Sophie D.. Université Paris Diderot - Paris 7; Francia. Université de la Réunion; Francia. Université des Antilles; Francia. Institut National de la Transfusion Sanguine;
Fil: Le Van Kim, Caroline. Institut National de la Transfusion Sanguine; . Université de la Réunion; Francia. Université Paris Diderot - Paris 7; Francia. Université des Antilles; Francia
Fil: Bihel, Frederic. University of Strasbourg; Francia
Fil: Schwarzbaum, Pablo Julio. 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. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina
Fil: Ostuni, Mariano. Université Paris Diderot - Paris 7; Francia. Université de la Réunion; Francia. Institut National de la Transfusion Sanguine; . Université des Antilles; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
TSPO
ANT
CHOLESTEROL
ATP RELEASE
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:11336/102745
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/102745
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO LigandsMarginedas-Freixa, IreneAlvarez, Cora LiliaMoras, MartinaHattab, ClaudeBouyer, GuillaumeChene, ArnaudLefevre, Sophie D.Le Van Kim, CarolineBihel, FredericSchwarzbaum, Pablo JulioOstuni, MarianoTSPOANTCHOLESTEROLATP RELEASEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Two main isoforms of the Translocator Protein (TSPO) have been identified. TSPO1 isubiquitous and is mainly present at the outer mitochondrial membrane of most eukaryotic cells,whereas, TSPO2 is specific to the erythroid lineage, located at the plasma membrane, the nucleus,and the endoplasmic reticulum. The design of specific tools is necessary to determine the molecularassociations and functions of TSPO, which remain controversial nowadays. We recently demonstratedthat TSPO2 is involved in a supramolecular complex of the erythrocyte membrane, where micromolardoses of the classical TSPO ligands induce ATP release and zinc protoporphyrin (ZnPPIX) transport.In this work, three newly-designed ligands (NCS1016, NCS1018, and NCS1026) were assessed fortheir ability to modulate the functions of various erythrocyte?s and compare them to the TSPOclassical ligands. The three new ligands were effective in reducing intraerythrocytic Plasmodiumgrowth, without compromising erythrocyte survival. While NCS1016 and NCS1018 were the mosteffective ligands in delaying sorbitol-induced hemolysis, NCS1016 induced the highest uptake ofZnPPIX and NCS1026 was the only ligand inhibiting the cholesterol uptake. Differential effects ofligands are probably due, not only, to ligand features, but also to the dynamic interaction of TSPOwith various partners at the cell membrane. Further studies are necessary to fully understand themechanisms of the TSPO's complex activation.Fil: Marginedas-Freixa, Irene. Institut National de la Transfusion Sanguine; . Université Paris Diderot - Paris 7; Francia. Université de la Réunion; Francia. Université des Antilles; FranciaFil: Alvarez, Cora Lilia. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; ArgentinaFil: Moras, Martina. Université des Antilles; Francia. Institut National de la Transfusion Sanguine; . Université de la Réunion; Francia. Université Paris Diderot - Paris 7; FranciaFil: Hattab, Claude. Université de la Réunion; Francia. Université Paris Diderot - Paris 7; Francia. Université des Antilles; Francia. Institut National de la Transfusion Sanguine; Fil: Bouyer, Guillaume. Sorbonne Université; FranciaFil: Chene, Arnaud. Université de la Réunion; Francia. Université des Antilles; Francia. Institut National de la Transfusion Sanguine; . Université Paris Diderot - Paris 7; FranciaFil: Lefevre, Sophie D.. Université Paris Diderot - Paris 7; Francia. Université de la Réunion; Francia. Université des Antilles; Francia. Institut National de la Transfusion Sanguine; Fil: Le Van Kim, Caroline. Institut National de la Transfusion Sanguine; . Université de la Réunion; Francia. Université Paris Diderot - Paris 7; Francia. Université des Antilles; FranciaFil: Bihel, Frederic. University of Strasbourg; FranciaFil: Schwarzbaum, Pablo Julio. 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. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; ArgentinaFil: Ostuni, Mariano. Université Paris Diderot - Paris 7; Francia. Université de la Réunion; Francia. Institut National de la Transfusion Sanguine; . Université des Antilles; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMolecular Diversity Preservation International2018-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/102745Marginedas-Freixa, Irene; Alvarez, Cora Lilia; Moras, Martina; Hattab, Claude; Bouyer, Guillaume; et al.; Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO Ligands; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 19; 10; 10-20181422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.mdpi.com/1422-0067/19/10/3098info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms19103098info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:29:06Zoai:ri.conicet.gov.ar:11336/102745instacron: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 10:29:06.766CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO Ligands
title Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO Ligands
spellingShingle Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO Ligands
Marginedas-Freixa, Irene
TSPO
ANT
CHOLESTEROL
ATP RELEASE
title_short Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO Ligands
title_full Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO Ligands
title_fullStr Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO Ligands
title_full_unstemmed Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO Ligands
title_sort Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO Ligands
dc.creator.none.fl_str_mv Marginedas-Freixa, Irene
Alvarez, Cora Lilia
Moras, Martina
Hattab, Claude
Bouyer, Guillaume
Chene, Arnaud
Lefevre, Sophie D.
Le Van Kim, Caroline
Bihel, Frederic
Schwarzbaum, Pablo Julio
Ostuni, Mariano
author Marginedas-Freixa, Irene
author_facet Marginedas-Freixa, Irene
Alvarez, Cora Lilia
Moras, Martina
Hattab, Claude
Bouyer, Guillaume
Chene, Arnaud
Lefevre, Sophie D.
Le Van Kim, Caroline
Bihel, Frederic
Schwarzbaum, Pablo Julio
Ostuni, Mariano
author_role author
author2 Alvarez, Cora Lilia
Moras, Martina
Hattab, Claude
Bouyer, Guillaume
Chene, Arnaud
Lefevre, Sophie D.
Le Van Kim, Caroline
Bihel, Frederic
Schwarzbaum, Pablo Julio
Ostuni, Mariano
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TSPO
ANT
CHOLESTEROL
ATP RELEASE
topic TSPO
ANT
CHOLESTEROL
ATP RELEASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Two main isoforms of the Translocator Protein (TSPO) have been identified. TSPO1 isubiquitous and is mainly present at the outer mitochondrial membrane of most eukaryotic cells,whereas, TSPO2 is specific to the erythroid lineage, located at the plasma membrane, the nucleus,and the endoplasmic reticulum. The design of specific tools is necessary to determine the molecularassociations and functions of TSPO, which remain controversial nowadays. We recently demonstratedthat TSPO2 is involved in a supramolecular complex of the erythrocyte membrane, where micromolardoses of the classical TSPO ligands induce ATP release and zinc protoporphyrin (ZnPPIX) transport.In this work, three newly-designed ligands (NCS1016, NCS1018, and NCS1026) were assessed fortheir ability to modulate the functions of various erythrocyte?s and compare them to the TSPOclassical ligands. The three new ligands were effective in reducing intraerythrocytic Plasmodiumgrowth, without compromising erythrocyte survival. While NCS1016 and NCS1018 were the mosteffective ligands in delaying sorbitol-induced hemolysis, NCS1016 induced the highest uptake ofZnPPIX and NCS1026 was the only ligand inhibiting the cholesterol uptake. Differential effects ofligands are probably due, not only, to ligand features, but also to the dynamic interaction of TSPOwith various partners at the cell membrane. Further studies are necessary to fully understand themechanisms of the TSPO's complex activation.
Fil: Marginedas-Freixa, Irene. Institut National de la Transfusion Sanguine; . Université Paris Diderot - Paris 7; Francia. Université de la Réunion; Francia. Université des Antilles; Francia
Fil: Alvarez, Cora Lilia. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; Argentina
Fil: Moras, Martina. Université des Antilles; Francia. Institut National de la Transfusion Sanguine; . Université de la Réunion; Francia. Université Paris Diderot - Paris 7; Francia
Fil: Hattab, Claude. Université de la Réunion; Francia. Université Paris Diderot - Paris 7; Francia. Université des Antilles; Francia. Institut National de la Transfusion Sanguine;
Fil: Bouyer, Guillaume. Sorbonne Université; Francia
Fil: Chene, Arnaud. Université de la Réunion; Francia. Université des Antilles; Francia. Institut National de la Transfusion Sanguine; . Université Paris Diderot - Paris 7; Francia
Fil: Lefevre, Sophie D.. Université Paris Diderot - Paris 7; Francia. Université de la Réunion; Francia. Université des Antilles; Francia. Institut National de la Transfusion Sanguine;
Fil: Le Van Kim, Caroline. Institut National de la Transfusion Sanguine; . Université de la Réunion; Francia. Université Paris Diderot - Paris 7; Francia. Université des Antilles; Francia
Fil: Bihel, Frederic. University of Strasbourg; Francia
Fil: Schwarzbaum, Pablo Julio. 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. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina
Fil: Ostuni, Mariano. Université Paris Diderot - Paris 7; Francia. Université de la Réunion; Francia. Institut National de la Transfusion Sanguine; . Université des Antilles; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Two main isoforms of the Translocator Protein (TSPO) have been identified. TSPO1 isubiquitous and is mainly present at the outer mitochondrial membrane of most eukaryotic cells,whereas, TSPO2 is specific to the erythroid lineage, located at the plasma membrane, the nucleus,and the endoplasmic reticulum. The design of specific tools is necessary to determine the molecularassociations and functions of TSPO, which remain controversial nowadays. We recently demonstratedthat TSPO2 is involved in a supramolecular complex of the erythrocyte membrane, where micromolardoses of the classical TSPO ligands induce ATP release and zinc protoporphyrin (ZnPPIX) transport.In this work, three newly-designed ligands (NCS1016, NCS1018, and NCS1026) were assessed fortheir ability to modulate the functions of various erythrocyte?s and compare them to the TSPOclassical ligands. The three new ligands were effective in reducing intraerythrocytic Plasmodiumgrowth, without compromising erythrocyte survival. While NCS1016 and NCS1018 were the mosteffective ligands in delaying sorbitol-induced hemolysis, NCS1016 induced the highest uptake ofZnPPIX and NCS1026 was the only ligand inhibiting the cholesterol uptake. Differential effects ofligands are probably due, not only, to ligand features, but also to the dynamic interaction of TSPOwith various partners at the cell membrane. Further studies are necessary to fully understand themechanisms of the TSPO's complex activation.
publishDate 2018
dc.date.none.fl_str_mv 2018-10
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/11336/102745
Marginedas-Freixa, Irene; Alvarez, Cora Lilia; Moras, Martina; Hattab, Claude; Bouyer, Guillaume; et al.; Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO Ligands; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 19; 10; 10-2018
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/102745
identifier_str_mv Marginedas-Freixa, Irene; Alvarez, Cora Lilia; Moras, Martina; Hattab, Claude; Bouyer, Guillaume; et al.; Induction of ATP Release, PPIX Transport, and Cholesterol Uptake by Human Red Blood Cells Using a New Family of TSPO Ligands; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 19; 10; 10-2018
1422-0067
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.mdpi.com/1422-0067/19/10/3098
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms19103098
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
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
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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