The flight response induces the release of an ILP from the intestine to inhibit cytoprotective mechanisms in C. Elegans

Autores
Veuthey, Tania Vanesa; Giunti, Sebastián; de Rosa, Maria Jose; Rayes, Diego Hernán
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The perpetuation of the flight response inhibits defensive cytoprotective mechanisms, leading to reduced resistance to environmental stressors, early onset of age-related disorders and shorter lifespan from invertebrates to mammals. We have recently shown that, in Caenorhabditis elegans, the flight response induces the neuronal release of Tyramine (TA, the invertebrate analog of adrenaline), which stimulates the adrenergic-like receptor TYRA-3 in the intestine. This leads to the activation of the DAF-2/Insulin/IGF-1 pathway and the inhibition of cytoprotective mechanisms, such as translocation of DAF-16/FOXO or HSF-1, not only in the intestine but also in other tissues. However, the signals that bridge the stimulation of TYRA-3 in the intestine with the activation of the DAF-2 insulin receptor in other tissues remain unknown. C. elegans genome encodes 40 Insulin-like peptides (ILPs), which in principle could bind to DAF-2, and many of them are expressed in the intestine. We, therefore, used RNAi to individually silence intestinal ILPs and test the resistance to environmental stressors such as oxidative and thermal stress. We found that the silencing of one of those ILPS, ins-3, improves the resistance to environmental stressors. In contrast to control, the addition of exogenous TA does not impair the oxidative or thermal stress resistance in ins-3-silenced animals. Moreover, we generated double null mutants of ins-3 and TAdeficient mutants and found that this double mutant is as resistant to environmental stress as single mutants. This suggests that tyramine and INS3 act in the same pathway to control stress resistance. Since ins-3 is also expressed in neurons, we injected ins-3 cDNA driven by intestinal and neuronal promoters to ins-3 null mutant animals, to assess the tissue where the expression of ins-3 is relevant for controlling stress resistance. We found that only intestinal expression of ins-3 restores the resistance to wild-type levels. Moreover, we found that the stress resistance of ins-3 null mutants is mediated, at least partially, by DAF-16/FOXO. We, therefore, propose that the activation of the intestinal GPCR TYRA-3 by the escape neurohormone TA leads to the release of INS-3 which acts as endocrine, autocrine and/or paracrine signal to activate the insulin receptor DAF-2 not only in the intestine but also in distal tissues. Given the high degree of conservation of fundamental mechanisms among species, this study can contribute to understanding molecular pathways and cellular communication involved in neural regulation of stress response in multicellular organisms.
Fil: Veuthey, Tania Vanesa. 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: Giunti, Sebastián. 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: de Rosa, Maria Jose. 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: Rayes, Diego Hernán. 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
Congreso de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
Salta
Argentina
Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
Panamerican Association for Biochemistry and Molecular Biology
Materia
INSULIN
STRESS
C.ELEGANS
LIFESPAN
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:11336/189954
Acceder
id CONICETDig_7d304decebb8a30071b02f4abcb3db4b
oai_identifier_str oai:ri.conicet.gov.ar:11336/189954
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The flight response induces the release of an ILP from the intestine to inhibit cytoprotective mechanisms in C. ElegansVeuthey, Tania VanesaGiunti, Sebastiánde Rosa, Maria JoseRayes, Diego HernánINSULINSTRESSC.ELEGANSLIFESPANhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The perpetuation of the flight response inhibits defensive cytoprotective mechanisms, leading to reduced resistance to environmental stressors, early onset of age-related disorders and shorter lifespan from invertebrates to mammals. We have recently shown that, in Caenorhabditis elegans, the flight response induces the neuronal release of Tyramine (TA, the invertebrate analog of adrenaline), which stimulates the adrenergic-like receptor TYRA-3 in the intestine. This leads to the activation of the DAF-2/Insulin/IGF-1 pathway and the inhibition of cytoprotective mechanisms, such as translocation of DAF-16/FOXO or HSF-1, not only in the intestine but also in other tissues. However, the signals that bridge the stimulation of TYRA-3 in the intestine with the activation of the DAF-2 insulin receptor in other tissues remain unknown. C. elegans genome encodes 40 Insulin-like peptides (ILPs), which in principle could bind to DAF-2, and many of them are expressed in the intestine. We, therefore, used RNAi to individually silence intestinal ILPs and test the resistance to environmental stressors such as oxidative and thermal stress. We found that the silencing of one of those ILPS, ins-3, improves the resistance to environmental stressors. In contrast to control, the addition of exogenous TA does not impair the oxidative or thermal stress resistance in ins-3-silenced animals. Moreover, we generated double null mutants of ins-3 and TAdeficient mutants and found that this double mutant is as resistant to environmental stress as single mutants. This suggests that tyramine and INS3 act in the same pathway to control stress resistance. Since ins-3 is also expressed in neurons, we injected ins-3 cDNA driven by intestinal and neuronal promoters to ins-3 null mutant animals, to assess the tissue where the expression of ins-3 is relevant for controlling stress resistance. We found that only intestinal expression of ins-3 restores the resistance to wild-type levels. Moreover, we found that the stress resistance of ins-3 null mutants is mediated, at least partially, by DAF-16/FOXO. We, therefore, propose that the activation of the intestinal GPCR TYRA-3 by the escape neurohormone TA leads to the release of INS-3 which acts as endocrine, autocrine and/or paracrine signal to activate the insulin receptor DAF-2 not only in the intestine but also in distal tissues. Given the high degree of conservation of fundamental mechanisms among species, this study can contribute to understanding molecular pathways and cellular communication involved in neural regulation of stress response in multicellular organisms.Fil: Veuthey, Tania Vanesa. 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: Giunti, Sebastián. 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: de Rosa, Maria Jose. 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: Rayes, Diego Hernán. 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; ArgentinaCongreso de la Sociedad Argentina de Investigaciones en Bioquímica y Biología MolecularSaltaArgentinaSociedad Argentina de Investigaciones en Bioquímica y Biología MolecularPanamerican Association for Biochemistry and Molecular BiologySociedad Argentina de Investigaciones en Bioquímica y Biología Molecular (SAIB).2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/189954The flight response induces the release of an ILP from the intestine to inhibit cytoprotective mechanisms in C. Elegans; Congreso de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular; Salta; Argentina; 2019; 50-511667-5746CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://newsite.saib.org.ar/publicaciones/info:eu-repo/semantics/altIdentifier/url/https://saib.org.ar/archivos/biocell-43.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:38:33Zoai:ri.conicet.gov.ar:11336/189954instacron: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 09:38:33.634CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The flight response induces the release of an ILP from the intestine to inhibit cytoprotective mechanisms in C. Elegans
title The flight response induces the release of an ILP from the intestine to inhibit cytoprotective mechanisms in C. Elegans
spellingShingle The flight response induces the release of an ILP from the intestine to inhibit cytoprotective mechanisms in C. Elegans
Veuthey, Tania Vanesa
INSULIN
STRESS
C.ELEGANS
LIFESPAN
title_short The flight response induces the release of an ILP from the intestine to inhibit cytoprotective mechanisms in C. Elegans
title_full The flight response induces the release of an ILP from the intestine to inhibit cytoprotective mechanisms in C. Elegans
title_fullStr The flight response induces the release of an ILP from the intestine to inhibit cytoprotective mechanisms in C. Elegans
title_full_unstemmed The flight response induces the release of an ILP from the intestine to inhibit cytoprotective mechanisms in C. Elegans
title_sort The flight response induces the release of an ILP from the intestine to inhibit cytoprotective mechanisms in C. Elegans
dc.creator.none.fl_str_mv Veuthey, Tania Vanesa
Giunti, Sebastián
de Rosa, Maria Jose
Rayes, Diego Hernán
author Veuthey, Tania Vanesa
author_facet Veuthey, Tania Vanesa
Giunti, Sebastián
de Rosa, Maria Jose
Rayes, Diego Hernán
author_role author
author2 Giunti, Sebastián
de Rosa, Maria Jose
Rayes, Diego Hernán
author2_role author
author
author
dc.subject.none.fl_str_mv INSULIN
STRESS
C.ELEGANS
LIFESPAN
topic INSULIN
STRESS
C.ELEGANS
LIFESPAN
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 perpetuation of the flight response inhibits defensive cytoprotective mechanisms, leading to reduced resistance to environmental stressors, early onset of age-related disorders and shorter lifespan from invertebrates to mammals. We have recently shown that, in Caenorhabditis elegans, the flight response induces the neuronal release of Tyramine (TA, the invertebrate analog of adrenaline), which stimulates the adrenergic-like receptor TYRA-3 in the intestine. This leads to the activation of the DAF-2/Insulin/IGF-1 pathway and the inhibition of cytoprotective mechanisms, such as translocation of DAF-16/FOXO or HSF-1, not only in the intestine but also in other tissues. However, the signals that bridge the stimulation of TYRA-3 in the intestine with the activation of the DAF-2 insulin receptor in other tissues remain unknown. C. elegans genome encodes 40 Insulin-like peptides (ILPs), which in principle could bind to DAF-2, and many of them are expressed in the intestine. We, therefore, used RNAi to individually silence intestinal ILPs and test the resistance to environmental stressors such as oxidative and thermal stress. We found that the silencing of one of those ILPS, ins-3, improves the resistance to environmental stressors. In contrast to control, the addition of exogenous TA does not impair the oxidative or thermal stress resistance in ins-3-silenced animals. Moreover, we generated double null mutants of ins-3 and TAdeficient mutants and found that this double mutant is as resistant to environmental stress as single mutants. This suggests that tyramine and INS3 act in the same pathway to control stress resistance. Since ins-3 is also expressed in neurons, we injected ins-3 cDNA driven by intestinal and neuronal promoters to ins-3 null mutant animals, to assess the tissue where the expression of ins-3 is relevant for controlling stress resistance. We found that only intestinal expression of ins-3 restores the resistance to wild-type levels. Moreover, we found that the stress resistance of ins-3 null mutants is mediated, at least partially, by DAF-16/FOXO. We, therefore, propose that the activation of the intestinal GPCR TYRA-3 by the escape neurohormone TA leads to the release of INS-3 which acts as endocrine, autocrine and/or paracrine signal to activate the insulin receptor DAF-2 not only in the intestine but also in distal tissues. Given the high degree of conservation of fundamental mechanisms among species, this study can contribute to understanding molecular pathways and cellular communication involved in neural regulation of stress response in multicellular organisms.
Fil: Veuthey, Tania Vanesa. 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: Giunti, Sebastián. 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: de Rosa, Maria Jose. 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: Rayes, Diego Hernán. 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
Congreso de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
Salta
Argentina
Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
Panamerican Association for Biochemistry and Molecular Biology
description The perpetuation of the flight response inhibits defensive cytoprotective mechanisms, leading to reduced resistance to environmental stressors, early onset of age-related disorders and shorter lifespan from invertebrates to mammals. We have recently shown that, in Caenorhabditis elegans, the flight response induces the neuronal release of Tyramine (TA, the invertebrate analog of adrenaline), which stimulates the adrenergic-like receptor TYRA-3 in the intestine. This leads to the activation of the DAF-2/Insulin/IGF-1 pathway and the inhibition of cytoprotective mechanisms, such as translocation of DAF-16/FOXO or HSF-1, not only in the intestine but also in other tissues. However, the signals that bridge the stimulation of TYRA-3 in the intestine with the activation of the DAF-2 insulin receptor in other tissues remain unknown. C. elegans genome encodes 40 Insulin-like peptides (ILPs), which in principle could bind to DAF-2, and many of them are expressed in the intestine. We, therefore, used RNAi to individually silence intestinal ILPs and test the resistance to environmental stressors such as oxidative and thermal stress. We found that the silencing of one of those ILPS, ins-3, improves the resistance to environmental stressors. In contrast to control, the addition of exogenous TA does not impair the oxidative or thermal stress resistance in ins-3-silenced animals. Moreover, we generated double null mutants of ins-3 and TAdeficient mutants and found that this double mutant is as resistant to environmental stress as single mutants. This suggests that tyramine and INS3 act in the same pathway to control stress resistance. Since ins-3 is also expressed in neurons, we injected ins-3 cDNA driven by intestinal and neuronal promoters to ins-3 null mutant animals, to assess the tissue where the expression of ins-3 is relevant for controlling stress resistance. We found that only intestinal expression of ins-3 restores the resistance to wild-type levels. Moreover, we found that the stress resistance of ins-3 null mutants is mediated, at least partially, by DAF-16/FOXO. We, therefore, propose that the activation of the intestinal GPCR TYRA-3 by the escape neurohormone TA leads to the release of INS-3 which acts as endocrine, autocrine and/or paracrine signal to activate the insulin receptor DAF-2 not only in the intestine but also in distal tissues. Given the high degree of conservation of fundamental mechanisms among species, this study can contribute to understanding molecular pathways and cellular communication involved in neural regulation of stress response in multicellular organisms.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Journal
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/11336/189954
The flight response induces the release of an ILP from the intestine to inhibit cytoprotective mechanisms in C. Elegans; Congreso de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular; Salta; Argentina; 2019; 50-51
1667-5746
CONICET Digital
CONICET
url http://hdl.handle.net/11336/189954
identifier_str_mv The flight response induces the release of an ILP from the intestine to inhibit cytoprotective mechanisms in C. Elegans; Congreso de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular; Salta; Argentina; 2019; 50-51
1667-5746
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/https://saib.org.ar/archivos/biocell-43.pdf
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/
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application/pdf
application/pdf
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dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular (SAIB).
publisher.none.fl_str_mv Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular (SAIB).
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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reponame_str CONICET Digital (CONICET)
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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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