Neural modulation of systemic stress response requires the insulin like-peptide INS-3

Autores
Veuthey, Tania Vanesa; Giunti, Sebastián; de Rosa, Maria Jos; Alkema, Mark; Rayes, Diego Hernán
Año de publicación
2023
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Throughout the animal kingdom, the perpetuation of the flight response leads to reduced ability to cope with environmental challenges, a drastic lifespan reduction, and an increase in disease susceptibility. We showed that, in C. elegans, the tyraminergic neuron RIM supplies a state- dependent neural switch between acute flight and long-term environmental stress responses. During the flight-stress response RIM neurons release TA, which stimulates the intestinal adrenergic-like receptor TYRA-3. This leads to DAF-2/Insulin/IGF- 1 pathway activation and inhibition of cytoprotective mechanisms in the intestine and other tissues. We hypothesized that TYRA-3 stimulates the release of Insulin-Like Peptides (ILPs) from the intestine that can systemically activate the DAF-2 insulin/ IGF1 receptors. We focused on strong agonist ILPs that are expressed in the intestine (INS-3, -4, -6, -32, and DAF-28). We found that ins-3 mutants are resistant to both heat and oxidative stress, much like tyra-3 mutants. Moreover, ins-3 mutants are resistant to the impairment of stress resistance upon exposure to exogenous tyramine. In addition, ins-3;tyra-3 double mutants are as resistant to environmental stress as single mutants, suggesting that both genes act in the same pathway. Since ins-3 is expressed in neurons and the intestine, we performed tissue-specific rescue experiments. We found that expression of ins-3 in the intestine restores stress resistance to wild-type levels. Taken together, our results suggest that intestinal activation of TYRA-3 by the escape neurohormone TA leads to INS-3 release which acts as an endocrine, autocrine, and/or paracrine signal to activate DAF-2 in different tissues.
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
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
Fil: de Rosa, Maria Jos. 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: Alkema, Mark. University Of Massachussets. Medical School. School Of Medicine; Estados Unidos
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
Third Latin American Worm Meeting
Valparaiso
Chile
Centro Interdisciplinario de Neurociencia Valparaíso
Materia
C. ELEGANS
STRESS RESPONSE
INSULINE
NEURONAL MODULATION
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:11336/250662

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network_name_str CONICET Digital (CONICET)
spelling Neural modulation of systemic stress response requires the insulin like-peptide INS-3Veuthey, Tania VanesaGiunti, Sebastiánde Rosa, Maria JosAlkema, MarkRayes, Diego HernánC. ELEGANSSTRESS RESPONSEINSULINENEURONAL MODULATIONhttps://purl.org/becyt/ford/1.7https://purl.org/becyt/ford/1Throughout the animal kingdom, the perpetuation of the flight response leads to reduced ability to cope with environmental challenges, a drastic lifespan reduction, and an increase in disease susceptibility. We showed that, in C. elegans, the tyraminergic neuron RIM supplies a state- dependent neural switch between acute flight and long-term environmental stress responses. During the flight-stress response RIM neurons release TA, which stimulates the intestinal adrenergic-like receptor TYRA-3. This leads to DAF-2/Insulin/IGF- 1 pathway activation and inhibition of cytoprotective mechanisms in the intestine and other tissues. We hypothesized that TYRA-3 stimulates the release of Insulin-Like Peptides (ILPs) from the intestine that can systemically activate the DAF-2 insulin/ IGF1 receptors. We focused on strong agonist ILPs that are expressed in the intestine (INS-3, -4, -6, -32, and DAF-28). We found that ins-3 mutants are resistant to both heat and oxidative stress, much like tyra-3 mutants. Moreover, ins-3 mutants are resistant to the impairment of stress resistance upon exposure to exogenous tyramine. In addition, ins-3;tyra-3 double mutants are as resistant to environmental stress as single mutants, suggesting that both genes act in the same pathway. Since ins-3 is expressed in neurons and the intestine, we performed tissue-specific rescue experiments. We found that expression of ins-3 in the intestine restores stress resistance to wild-type levels. Taken together, our results suggest that intestinal activation of TYRA-3 by the escape neurohormone TA leads to INS-3 release which acts as an endocrine, autocrine, and/or paracrine signal to activate DAF-2 in different tissues.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; 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; ArgentinaFil: de Rosa, Maria Jos. 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: Alkema, Mark. University Of Massachussets. Medical School. School Of Medicine; Estados UnidosFil: 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; ArgentinaThird Latin American Worm MeetingValparaisoChileCentro Interdisciplinario de Neurociencia ValparaísoLatin American worm meeting2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/250662Neural modulation of systemic stress response requires the insulin like-peptide INS-3; Third Latin American Worm Meeting; Valparaiso; Chile; 2023; 42-42CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://cinv.uv.cl/en/3rd-la-worm-meeting/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:35:59Zoai:ri.conicet.gov.ar:11336/250662instacron: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 09:35:59.479CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Neural modulation of systemic stress response requires the insulin like-peptide INS-3
title Neural modulation of systemic stress response requires the insulin like-peptide INS-3
spellingShingle Neural modulation of systemic stress response requires the insulin like-peptide INS-3
Veuthey, Tania Vanesa
C. ELEGANS
STRESS RESPONSE
INSULINE
NEURONAL MODULATION
title_short Neural modulation of systemic stress response requires the insulin like-peptide INS-3
title_full Neural modulation of systemic stress response requires the insulin like-peptide INS-3
title_fullStr Neural modulation of systemic stress response requires the insulin like-peptide INS-3
title_full_unstemmed Neural modulation of systemic stress response requires the insulin like-peptide INS-3
title_sort Neural modulation of systemic stress response requires the insulin like-peptide INS-3
dc.creator.none.fl_str_mv Veuthey, Tania Vanesa
Giunti, Sebastián
de Rosa, Maria Jos
Alkema, Mark
Rayes, Diego Hernán
author Veuthey, Tania Vanesa
author_facet Veuthey, Tania Vanesa
Giunti, Sebastián
de Rosa, Maria Jos
Alkema, Mark
Rayes, Diego Hernán
author_role author
author2 Giunti, Sebastián
de Rosa, Maria Jos
Alkema, Mark
Rayes, Diego Hernán
author2_role author
author
author
author
dc.subject.none.fl_str_mv C. ELEGANS
STRESS RESPONSE
INSULINE
NEURONAL MODULATION
topic C. ELEGANS
STRESS RESPONSE
INSULINE
NEURONAL MODULATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.7
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Throughout the animal kingdom, the perpetuation of the flight response leads to reduced ability to cope with environmental challenges, a drastic lifespan reduction, and an increase in disease susceptibility. We showed that, in C. elegans, the tyraminergic neuron RIM supplies a state- dependent neural switch between acute flight and long-term environmental stress responses. During the flight-stress response RIM neurons release TA, which stimulates the intestinal adrenergic-like receptor TYRA-3. This leads to DAF-2/Insulin/IGF- 1 pathway activation and inhibition of cytoprotective mechanisms in the intestine and other tissues. We hypothesized that TYRA-3 stimulates the release of Insulin-Like Peptides (ILPs) from the intestine that can systemically activate the DAF-2 insulin/ IGF1 receptors. We focused on strong agonist ILPs that are expressed in the intestine (INS-3, -4, -6, -32, and DAF-28). We found that ins-3 mutants are resistant to both heat and oxidative stress, much like tyra-3 mutants. Moreover, ins-3 mutants are resistant to the impairment of stress resistance upon exposure to exogenous tyramine. In addition, ins-3;tyra-3 double mutants are as resistant to environmental stress as single mutants, suggesting that both genes act in the same pathway. Since ins-3 is expressed in neurons and the intestine, we performed tissue-specific rescue experiments. We found that expression of ins-3 in the intestine restores stress resistance to wild-type levels. Taken together, our results suggest that intestinal activation of TYRA-3 by the escape neurohormone TA leads to INS-3 release which acts as an endocrine, autocrine, and/or paracrine signal to activate DAF-2 in different tissues.
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
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
Fil: de Rosa, Maria Jos. 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: Alkema, Mark. University Of Massachussets. Medical School. School Of Medicine; Estados Unidos
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
Third Latin American Worm Meeting
Valparaiso
Chile
Centro Interdisciplinario de Neurociencia Valparaíso
description Throughout the animal kingdom, the perpetuation of the flight response leads to reduced ability to cope with environmental challenges, a drastic lifespan reduction, and an increase in disease susceptibility. We showed that, in C. elegans, the tyraminergic neuron RIM supplies a state- dependent neural switch between acute flight and long-term environmental stress responses. During the flight-stress response RIM neurons release TA, which stimulates the intestinal adrenergic-like receptor TYRA-3. This leads to DAF-2/Insulin/IGF- 1 pathway activation and inhibition of cytoprotective mechanisms in the intestine and other tissues. We hypothesized that TYRA-3 stimulates the release of Insulin-Like Peptides (ILPs) from the intestine that can systemically activate the DAF-2 insulin/ IGF1 receptors. We focused on strong agonist ILPs that are expressed in the intestine (INS-3, -4, -6, -32, and DAF-28). We found that ins-3 mutants are resistant to both heat and oxidative stress, much like tyra-3 mutants. Moreover, ins-3 mutants are resistant to the impairment of stress resistance upon exposure to exogenous tyramine. In addition, ins-3;tyra-3 double mutants are as resistant to environmental stress as single mutants, suggesting that both genes act in the same pathway. Since ins-3 is expressed in neurons and the intestine, we performed tissue-specific rescue experiments. We found that expression of ins-3 in the intestine restores stress resistance to wild-type levels. Taken together, our results suggest that intestinal activation of TYRA-3 by the escape neurohormone TA leads to INS-3 release which acts as an endocrine, autocrine, and/or paracrine signal to activate DAF-2 in different tissues.
publishDate 2023
dc.date.none.fl_str_mv 2023
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/11336/250662
Neural modulation of systemic stress response requires the insulin like-peptide INS-3; Third Latin American Worm Meeting; Valparaiso; Chile; 2023; 42-42
CONICET Digital
CONICET
url http://hdl.handle.net/11336/250662
identifier_str_mv Neural modulation of systemic stress response requires the insulin like-peptide INS-3; Third Latin American Worm Meeting; Valparaiso; Chile; 2023; 42-42
CONICET Digital
CONICET
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language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://cinv.uv.cl/en/3rd-la-worm-meeting/
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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
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application/pdf
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Latin American worm meeting
publisher.none.fl_str_mv Latin American worm meeting
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