Lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons

Autores
Borroni, Maria Virginia; Kamerbeek, Constanza Belén; Pediconi, Maria Filomena; Barrantes, Francisco Jose
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The effects of lovastatin, an inhibitor of cholesterol biosynthesis, on these two nAChRs endogenously expressed in rat hippocampal neuronal cells were evaluated in the 0.01–1 μM range. Chronic (14 days) lovastatin treatment augmented cell-surface levels of α7 and α4 nAChRs, as measured by fluorescence microscopy and radioactive ligand binding assays. This was accompanied in both cases by an increase in total protein receptor levels as determined by Western blots. At low lovastatin concentrations (10–100 nM), the increase in α4 nAChR in neurites was higher than in neuronal cell somata; the opposite occurred at higher (0.5–1 μM) lovastatin concentrations. In contrast, neurite α7 nAChRs raised more than somatic α7 nAChRs at all lovastatin concentrations tested. These results indicate that cholesterol levels homeostatically regulate α7 and α4 nAChR levels in a differential manner through mechanisms that depend on statin concentration and receptor localization. The neuroprotective pleomorphic effects of statins may act by reestablishing the homeostatic equilibrium.
Fil: Borroni, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnología en Polímeros y Nanotecnología. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnología en Polímeros y Nanotecnología; Argentina
Fil: Kamerbeek, Constanza Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Pediconi, Maria Filomena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Barrantes, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Materia
ALZHEIMER DISEASE
CHOLESTEROL
HIPPOCAMPAL NEURONS
HOMEOSTATIC REGULATION
NICOTINIC ACETYLCHOLINE RECEPTOR
UPREGULATION
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:11336/131393

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network_name_str CONICET Digital (CONICET)
spelling Lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neuronsBorroni, Maria VirginiaKamerbeek, Constanza BelénPediconi, Maria FilomenaBarrantes, Francisco JoseALZHEIMER DISEASECHOLESTEROLHIPPOCAMPAL NEURONSHOMEOSTATIC REGULATIONNICOTINIC ACETYLCHOLINE RECEPTORUPREGULATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The effects of lovastatin, an inhibitor of cholesterol biosynthesis, on these two nAChRs endogenously expressed in rat hippocampal neuronal cells were evaluated in the 0.01–1 μM range. Chronic (14 days) lovastatin treatment augmented cell-surface levels of α7 and α4 nAChRs, as measured by fluorescence microscopy and radioactive ligand binding assays. This was accompanied in both cases by an increase in total protein receptor levels as determined by Western blots. At low lovastatin concentrations (10–100 nM), the increase in α4 nAChR in neurites was higher than in neuronal cell somata; the opposite occurred at higher (0.5–1 μM) lovastatin concentrations. In contrast, neurite α7 nAChRs raised more than somatic α7 nAChRs at all lovastatin concentrations tested. These results indicate that cholesterol levels homeostatically regulate α7 and α4 nAChR levels in a differential manner through mechanisms that depend on statin concentration and receptor localization. The neuroprotective pleomorphic effects of statins may act by reestablishing the homeostatic equilibrium.Fil: Borroni, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnología en Polímeros y Nanotecnología. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnología en Polímeros y Nanotecnología; ArgentinaFil: Kamerbeek, Constanza Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Pediconi, Maria Filomena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Barrantes, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaMolecular Diversity Preservation International2020-10info: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/11336/131393Borroni, Maria Virginia; Kamerbeek, Constanza Belén; Pediconi, Maria Filomena; Barrantes, Francisco Jose; Lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons; Molecular Diversity Preservation International; Molecules; 25; 20; 10-2020; 1-161420-3049CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1420-3049/25/20/4838/htminfo:eu-repo/semantics/altIdentifier/doi/10.3390/molecules25204838info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:00:36Zoai:ri.conicet.gov.ar:11336/131393instacron: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:34982025-09-03 10:00:36.985CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons
title Lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons
spellingShingle Lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons
Borroni, Maria Virginia
ALZHEIMER DISEASE
CHOLESTEROL
HIPPOCAMPAL NEURONS
HOMEOSTATIC REGULATION
NICOTINIC ACETYLCHOLINE RECEPTOR
UPREGULATION
title_short Lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons
title_full Lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons
title_fullStr Lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons
title_full_unstemmed Lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons
title_sort Lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons
dc.creator.none.fl_str_mv Borroni, Maria Virginia
Kamerbeek, Constanza Belén
Pediconi, Maria Filomena
Barrantes, Francisco Jose
author Borroni, Maria Virginia
author_facet Borroni, Maria Virginia
Kamerbeek, Constanza Belén
Pediconi, Maria Filomena
Barrantes, Francisco Jose
author_role author
author2 Kamerbeek, Constanza Belén
Pediconi, Maria Filomena
Barrantes, Francisco Jose
author2_role author
author
author
dc.subject.none.fl_str_mv ALZHEIMER DISEASE
CHOLESTEROL
HIPPOCAMPAL NEURONS
HOMEOSTATIC REGULATION
NICOTINIC ACETYLCHOLINE RECEPTOR
UPREGULATION
topic ALZHEIMER DISEASE
CHOLESTEROL
HIPPOCAMPAL NEURONS
HOMEOSTATIC REGULATION
NICOTINIC ACETYLCHOLINE RECEPTOR
UPREGULATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The effects of lovastatin, an inhibitor of cholesterol biosynthesis, on these two nAChRs endogenously expressed in rat hippocampal neuronal cells were evaluated in the 0.01–1 μM range. Chronic (14 days) lovastatin treatment augmented cell-surface levels of α7 and α4 nAChRs, as measured by fluorescence microscopy and radioactive ligand binding assays. This was accompanied in both cases by an increase in total protein receptor levels as determined by Western blots. At low lovastatin concentrations (10–100 nM), the increase in α4 nAChR in neurites was higher than in neuronal cell somata; the opposite occurred at higher (0.5–1 μM) lovastatin concentrations. In contrast, neurite α7 nAChRs raised more than somatic α7 nAChRs at all lovastatin concentrations tested. These results indicate that cholesterol levels homeostatically regulate α7 and α4 nAChR levels in a differential manner through mechanisms that depend on statin concentration and receptor localization. The neuroprotective pleomorphic effects of statins may act by reestablishing the homeostatic equilibrium.
Fil: Borroni, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnología en Polímeros y Nanotecnología. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnología en Polímeros y Nanotecnología; Argentina
Fil: Kamerbeek, Constanza Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Pediconi, Maria Filomena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Barrantes, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
description Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The effects of lovastatin, an inhibitor of cholesterol biosynthesis, on these two nAChRs endogenously expressed in rat hippocampal neuronal cells were evaluated in the 0.01–1 μM range. Chronic (14 days) lovastatin treatment augmented cell-surface levels of α7 and α4 nAChRs, as measured by fluorescence microscopy and radioactive ligand binding assays. This was accompanied in both cases by an increase in total protein receptor levels as determined by Western blots. At low lovastatin concentrations (10–100 nM), the increase in α4 nAChR in neurites was higher than in neuronal cell somata; the opposite occurred at higher (0.5–1 μM) lovastatin concentrations. In contrast, neurite α7 nAChRs raised more than somatic α7 nAChRs at all lovastatin concentrations tested. These results indicate that cholesterol levels homeostatically regulate α7 and α4 nAChR levels in a differential manner through mechanisms that depend on statin concentration and receptor localization. The neuroprotective pleomorphic effects of statins may act by reestablishing the homeostatic equilibrium.
publishDate 2020
dc.date.none.fl_str_mv 2020-10
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/11336/131393
Borroni, Maria Virginia; Kamerbeek, Constanza Belén; Pediconi, Maria Filomena; Barrantes, Francisco Jose; Lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons; Molecular Diversity Preservation International; Molecules; 25; 20; 10-2020; 1-16
1420-3049
CONICET Digital
CONICET
url http://hdl.handle.net/11336/131393
identifier_str_mv Borroni, Maria Virginia; Kamerbeek, Constanza Belén; Pediconi, Maria Filomena; Barrantes, Francisco Jose; Lovastatin differentially regulates α7 and α4 neuronal nicotinic acetylcholine receptor levels in rat hippocampal neurons; Molecular Diversity Preservation International; Molecules; 25; 20; 10-2020; 1-16
1420-3049
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1420-3049/25/20/4838/htm
info:eu-repo/semantics/altIdentifier/doi/10.3390/molecules25204838
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)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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