Exploring The α7 Nicotinic Receptor In Human Retinal Pigment Epithelium Cells As A Novel Therapeutic Target
- Autores
- Mader, Julieta Ailen; Fernandez Delias, María Florencia; Chrestia, Juan Facundo; Esandi, María del Carmen; Bouzat, Cecilia Beatriz
- Año de publicación
- 2024
- Idioma
- inglés
- Tipo de recurso
- documento de conferencia
- Estado
- versión publicada
- Descripción
- The α7 nicotinic acetylcholine receptor is highly expressed in the brain and is also present in non-neuronal cells, including immune and epithelial cells. It is involved in cognition, memory, pain, neuroprotection and inflammation and its potentiation has emerged as a therapeutic strategy for neurological, neurodegenerative, and inflammatory disorders. Given that the increase in oxidative stress in retinal pigment epithelial cells contributes to the development of age-related macular degeneration and that α7 activation exerts cell protective effects, we explored the presence and functional relevance of α7 in D407 retinal pigment epithelium cells, a model system for various retinal diseases. By real time PCR, and indirect immunofluorescence using confocalmicroscopy and flow cytometry we demonstrated the presence of α7 in these epithelial cells. To determine the presence of functional receptors, we measured the movement of intracellular calcium levels triggered by the activation of α7. A pulse of ACh together with an α7 positive allosteric modulator revealed a 3-fold increase in intracellular calcium measured with the fluo-3AM probe. To mimic the events occurring in age-related macular degeneration, we treated cells with ferric ammonium citrate (FAC) to induce stress damage andmeasured reactive oxygen species (ROS) with the fluorescent probe DCFH-DA. FAC treatment resulted in a significant increase in ROS levels with respect to the control. To determine if α7 protects against oxidative damage, we exposed cells to a specific α7 agonist, PNU-282987, before the FAC treatment. Notably, PNU-282987 exhibited protective effects against the damage, leading to a reduction in ROS levels compared to the treated cells. Overall, by identifying for the first time the presence of α7 in the D407 cell line and revealing its protective role against oxidative damage, we propose α7 as a promising therapeutic target for retinal neurodegenerative disorders.
Fil: Mader, Julieta Ailen. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Fernandez Delias, María Florencia. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Chrestia, Juan Facundo. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Esandi, María del Carmen. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. 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: Bouzat, Cecilia Beatriz. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental
Bahía Blanca
Argentina
Asociación Argentina De Farmacología Experimental - Materia
-
LIGAND-GATED ION CHANNEL
NICOTINIC RECEPTOR
EPITHELIAL CELLS
ALPHA7 - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/278078
Ver los metadatos del registro completo
| id |
CONICETDig_73cd761f7feccb2a08741144dfc4f81f |
|---|---|
| oai_identifier_str |
oai:ri.conicet.gov.ar:11336/278078 |
| network_acronym_str |
CONICETDig |
| repository_id_str |
3498 |
| network_name_str |
CONICET Digital (CONICET) |
| spelling |
Exploring The α7 Nicotinic Receptor In Human Retinal Pigment Epithelium Cells As A Novel Therapeutic TargetMader, Julieta AilenFernandez Delias, María FlorenciaChrestia, Juan FacundoEsandi, María del CarmenBouzat, Cecilia BeatrizLIGAND-GATED ION CHANNELNICOTINIC RECEPTOREPITHELIAL CELLSALPHA7https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The α7 nicotinic acetylcholine receptor is highly expressed in the brain and is also present in non-neuronal cells, including immune and epithelial cells. It is involved in cognition, memory, pain, neuroprotection and inflammation and its potentiation has emerged as a therapeutic strategy for neurological, neurodegenerative, and inflammatory disorders. Given that the increase in oxidative stress in retinal pigment epithelial cells contributes to the development of age-related macular degeneration and that α7 activation exerts cell protective effects, we explored the presence and functional relevance of α7 in D407 retinal pigment epithelium cells, a model system for various retinal diseases. By real time PCR, and indirect immunofluorescence using confocalmicroscopy and flow cytometry we demonstrated the presence of α7 in these epithelial cells. To determine the presence of functional receptors, we measured the movement of intracellular calcium levels triggered by the activation of α7. A pulse of ACh together with an α7 positive allosteric modulator revealed a 3-fold increase in intracellular calcium measured with the fluo-3AM probe. To mimic the events occurring in age-related macular degeneration, we treated cells with ferric ammonium citrate (FAC) to induce stress damage andmeasured reactive oxygen species (ROS) with the fluorescent probe DCFH-DA. FAC treatment resulted in a significant increase in ROS levels with respect to the control. To determine if α7 protects against oxidative damage, we exposed cells to a specific α7 agonist, PNU-282987, before the FAC treatment. Notably, PNU-282987 exhibited protective effects against the damage, leading to a reduction in ROS levels compared to the treated cells. Overall, by identifying for the first time the presence of α7 in the D407 cell line and revealing its protective role against oxidative damage, we propose α7 as a promising therapeutic target for retinal neurodegenerative disorders.Fil: Mader, Julieta Ailen. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Fernandez Delias, María Florencia. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Chrestia, Juan Facundo. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Esandi, María del Carmen. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. 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: Bouzat, Cecilia Beatriz. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaLVI Reunión Anual De La Asociación Argentina De Farmacología ExperimentalBahía BlancaArgentinaAsociación Argentina De Farmacología ExperimentalAsociación Argentina De Farmacología Experimental2024info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/278078Exploring The α7 Nicotinic Receptor In Human Retinal Pigment Epithelium Cells As A Novel Therapeutic Target; LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental; Bahía Blanca; Argentina; 2024; 108-108978-631-90806-0-5CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://aafeargentina.org/congresos-aafe/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T13:27:43Zoai:ri.conicet.gov.ar:11336/278078instacron: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:34982025-12-23 13:27:44.113CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Exploring The α7 Nicotinic Receptor In Human Retinal Pigment Epithelium Cells As A Novel Therapeutic Target |
| title |
Exploring The α7 Nicotinic Receptor In Human Retinal Pigment Epithelium Cells As A Novel Therapeutic Target |
| spellingShingle |
Exploring The α7 Nicotinic Receptor In Human Retinal Pigment Epithelium Cells As A Novel Therapeutic Target Mader, Julieta Ailen LIGAND-GATED ION CHANNEL NICOTINIC RECEPTOR EPITHELIAL CELLS ALPHA7 |
| title_short |
Exploring The α7 Nicotinic Receptor In Human Retinal Pigment Epithelium Cells As A Novel Therapeutic Target |
| title_full |
Exploring The α7 Nicotinic Receptor In Human Retinal Pigment Epithelium Cells As A Novel Therapeutic Target |
| title_fullStr |
Exploring The α7 Nicotinic Receptor In Human Retinal Pigment Epithelium Cells As A Novel Therapeutic Target |
| title_full_unstemmed |
Exploring The α7 Nicotinic Receptor In Human Retinal Pigment Epithelium Cells As A Novel Therapeutic Target |
| title_sort |
Exploring The α7 Nicotinic Receptor In Human Retinal Pigment Epithelium Cells As A Novel Therapeutic Target |
| dc.creator.none.fl_str_mv |
Mader, Julieta Ailen Fernandez Delias, María Florencia Chrestia, Juan Facundo Esandi, María del Carmen Bouzat, Cecilia Beatriz |
| author |
Mader, Julieta Ailen |
| author_facet |
Mader, Julieta Ailen Fernandez Delias, María Florencia Chrestia, Juan Facundo Esandi, María del Carmen Bouzat, Cecilia Beatriz |
| author_role |
author |
| author2 |
Fernandez Delias, María Florencia Chrestia, Juan Facundo Esandi, María del Carmen Bouzat, Cecilia Beatriz |
| author2_role |
author author author author |
| dc.subject.none.fl_str_mv |
LIGAND-GATED ION CHANNEL NICOTINIC RECEPTOR EPITHELIAL CELLS ALPHA7 |
| topic |
LIGAND-GATED ION CHANNEL NICOTINIC RECEPTOR EPITHELIAL CELLS ALPHA7 |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
The α7 nicotinic acetylcholine receptor is highly expressed in the brain and is also present in non-neuronal cells, including immune and epithelial cells. It is involved in cognition, memory, pain, neuroprotection and inflammation and its potentiation has emerged as a therapeutic strategy for neurological, neurodegenerative, and inflammatory disorders. Given that the increase in oxidative stress in retinal pigment epithelial cells contributes to the development of age-related macular degeneration and that α7 activation exerts cell protective effects, we explored the presence and functional relevance of α7 in D407 retinal pigment epithelium cells, a model system for various retinal diseases. By real time PCR, and indirect immunofluorescence using confocalmicroscopy and flow cytometry we demonstrated the presence of α7 in these epithelial cells. To determine the presence of functional receptors, we measured the movement of intracellular calcium levels triggered by the activation of α7. A pulse of ACh together with an α7 positive allosteric modulator revealed a 3-fold increase in intracellular calcium measured with the fluo-3AM probe. To mimic the events occurring in age-related macular degeneration, we treated cells with ferric ammonium citrate (FAC) to induce stress damage andmeasured reactive oxygen species (ROS) with the fluorescent probe DCFH-DA. FAC treatment resulted in a significant increase in ROS levels with respect to the control. To determine if α7 protects against oxidative damage, we exposed cells to a specific α7 agonist, PNU-282987, before the FAC treatment. Notably, PNU-282987 exhibited protective effects against the damage, leading to a reduction in ROS levels compared to the treated cells. Overall, by identifying for the first time the presence of α7 in the D407 cell line and revealing its protective role against oxidative damage, we propose α7 as a promising therapeutic target for retinal neurodegenerative disorders. Fil: Mader, Julieta Ailen. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Fernandez Delias, María Florencia. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Chrestia, Juan Facundo. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Esandi, María del Carmen. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. 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: Bouzat, Cecilia Beatriz. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental Bahía Blanca Argentina Asociación Argentina De Farmacología Experimental |
| description |
The α7 nicotinic acetylcholine receptor is highly expressed in the brain and is also present in non-neuronal cells, including immune and epithelial cells. It is involved in cognition, memory, pain, neuroprotection and inflammation and its potentiation has emerged as a therapeutic strategy for neurological, neurodegenerative, and inflammatory disorders. Given that the increase in oxidative stress in retinal pigment epithelial cells contributes to the development of age-related macular degeneration and that α7 activation exerts cell protective effects, we explored the presence and functional relevance of α7 in D407 retinal pigment epithelium cells, a model system for various retinal diseases. By real time PCR, and indirect immunofluorescence using confocalmicroscopy and flow cytometry we demonstrated the presence of α7 in these epithelial cells. To determine the presence of functional receptors, we measured the movement of intracellular calcium levels triggered by the activation of α7. A pulse of ACh together with an α7 positive allosteric modulator revealed a 3-fold increase in intracellular calcium measured with the fluo-3AM probe. To mimic the events occurring in age-related macular degeneration, we treated cells with ferric ammonium citrate (FAC) to induce stress damage andmeasured reactive oxygen species (ROS) with the fluorescent probe DCFH-DA. FAC treatment resulted in a significant increase in ROS levels with respect to the control. To determine if α7 protects against oxidative damage, we exposed cells to a specific α7 agonist, PNU-282987, before the FAC treatment. Notably, PNU-282987 exhibited protective effects against the damage, leading to a reduction in ROS levels compared to the treated cells. Overall, by identifying for the first time the presence of α7 in the D407 cell line and revealing its protective role against oxidative damage, we propose α7 as a promising therapeutic target for retinal neurodegenerative disorders. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/conferenceObject Congreso Book http://purl.org/coar/resource_type/c_5794 info:ar-repo/semantics/documentoDeConferencia |
| status_str |
publishedVersion |
| format |
conferenceObject |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/278078 Exploring The α7 Nicotinic Receptor In Human Retinal Pigment Epithelium Cells As A Novel Therapeutic Target; LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental; Bahía Blanca; Argentina; 2024; 108-108 978-631-90806-0-5 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/278078 |
| identifier_str_mv |
Exploring The α7 Nicotinic Receptor In Human Retinal Pigment Epithelium Cells As A Novel Therapeutic Target; LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental; Bahía Blanca; Argentina; 2024; 108-108 978-631-90806-0-5 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://aafeargentina.org/congresos-aafe/ |
| 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 application/pdf application/pdf application/pdf |
| dc.coverage.none.fl_str_mv |
Nacional |
| dc.publisher.none.fl_str_mv |
Asociación Argentina De Farmacología Experimental |
| publisher.none.fl_str_mv |
Asociación Argentina De Farmacología Experimental |
| 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_ |
1852335157176958976 |
| score |
12.952241 |