Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cell

Autores
Simpson, Peter D.; Eipper, Betty A.; Katz, Maximiliano Javier; Gándara, Lautaro; Wappner, Pablo; Fischer, Roman; Hodson, Emma J.; Ratcliffe, Peter J.; Masson, Norma
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Interactions between biological pathways and molecular oxygen require robust mechanisms for detecting and responding to changes in cellular oxygen availability, to support oxygen homeostasis. Peptidylglycine α-amidating monooxygenase (PAM) catalyzes a two-step reaction resulting in the C-terminal amidation of peptides, a process important for their stability and biological activity. Here we show that in human, mouse, and insect cells, peptide amidation is exquisitely sensitive to hypoxia. Different amidation events on chromogranin A, and on peptides processed from proopiomelanocortin, manifest similar striking sensitivity to hypoxia in a range of neuroendocrine cells, being progressively inhibited from mild (7% O2) to severe (1% O2) hypoxia. In developing Drosophila melanogaster larvae, FMRF amidation in thoracic ventral (Tv) neurons is strikingly suppressed by hypoxia. Our findings have thus defined a novel monooxygenase-based oxygen sensing mechanism that has the capacity to signal changes in oxygen availability to peptidergic pathways.
Fil: Simpson, Peter D.. University Of Oxford; Reino Unido
Fil: Eipper, Betty A.. University Of Connecticut; Estados Unidos
Fil: Katz, Maximiliano Javier. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
Fil: Gándara, Lautaro. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
Fil: Wappner, Pablo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
Fil: Fischer, Roman. University Of Oxford; Reino Unido
Fil: Hodson, Emma J.. University Of Oxford; Reino Unido
Fil: Ratcliffe, Peter J.. University Of Oxford; Reino Unido
Fil: Masson, Norma. University Of Oxford; Reino Unido
Materia
copper monooxygenase
hypoxia
amidated peptides
oxygen sensor
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/9757
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/9757
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine CellSimpson, Peter D.Eipper, Betty A.Katz, Maximiliano JavierGándara, LautaroWappner, PabloFischer, RomanHodson, Emma J.Ratcliffe, Peter J.Masson, Normacopper monooxygenasehypoxiaamidated peptidesoxygen sensorhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Interactions between biological pathways and molecular oxygen require robust mechanisms for detecting and responding to changes in cellular oxygen availability, to support oxygen homeostasis. Peptidylglycine α-amidating monooxygenase (PAM) catalyzes a two-step reaction resulting in the C-terminal amidation of peptides, a process important for their stability and biological activity. Here we show that in human, mouse, and insect cells, peptide amidation is exquisitely sensitive to hypoxia. Different amidation events on chromogranin A, and on peptides processed from proopiomelanocortin, manifest similar striking sensitivity to hypoxia in a range of neuroendocrine cells, being progressively inhibited from mild (7% O2) to severe (1% O2) hypoxia. In developing Drosophila melanogaster larvae, FMRF amidation in thoracic ventral (Tv) neurons is strikingly suppressed by hypoxia. Our findings have thus defined a novel monooxygenase-based oxygen sensing mechanism that has the capacity to signal changes in oxygen availability to peptidergic pathways.Fil: Simpson, Peter D.. University Of Oxford; Reino UnidoFil: Eipper, Betty A.. University Of Connecticut; Estados UnidosFil: Katz, Maximiliano Javier. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Gándara, Lautaro. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Wappner, Pablo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Fischer, Roman. University Of Oxford; Reino UnidoFil: Hodson, Emma J.. University Of Oxford; Reino UnidoFil: Ratcliffe, Peter J.. University Of Oxford; Reino UnidoFil: Masson, Norma. University Of Oxford; Reino UnidoAmerican Society For Biochemistry And Molecular Biology2015-10info: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/11336/9757Simpson, Peter D.; Eipper, Betty A.; Katz, Maximiliano Javier; Gándara, Lautaro; Wappner, Pablo; et al.; Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cell; American Society For Biochemistry And Molecular Biology; Journal Of Biological Chemistry; 290; 41; 10-2015; 24891-249010021-9258enginfo:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/290/41/24891.longinfo:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M115.667246info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:53:35Zoai:ri.conicet.gov.ar:11336/9757instacron: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:34982025-10-15 14:53:35.428CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cell
title Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cell
spellingShingle Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cell
Simpson, Peter D.
copper monooxygenase
hypoxia
amidated peptides
oxygen sensor
title_short Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cell
title_full Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cell
title_fullStr Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cell
title_full_unstemmed Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cell
title_sort Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cell
dc.creator.none.fl_str_mv Simpson, Peter D.
Eipper, Betty A.
Katz, Maximiliano Javier
Gándara, Lautaro
Wappner, Pablo
Fischer, Roman
Hodson, Emma J.
Ratcliffe, Peter J.
Masson, Norma
author Simpson, Peter D.
author_facet Simpson, Peter D.
Eipper, Betty A.
Katz, Maximiliano Javier
Gándara, Lautaro
Wappner, Pablo
Fischer, Roman
Hodson, Emma J.
Ratcliffe, Peter J.
Masson, Norma
author_role author
author2 Eipper, Betty A.
Katz, Maximiliano Javier
Gándara, Lautaro
Wappner, Pablo
Fischer, Roman
Hodson, Emma J.
Ratcliffe, Peter J.
Masson, Norma
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv copper monooxygenase
hypoxia
amidated peptides
oxygen sensor
topic copper monooxygenase
hypoxia
amidated peptides
oxygen sensor
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Interactions between biological pathways and molecular oxygen require robust mechanisms for detecting and responding to changes in cellular oxygen availability, to support oxygen homeostasis. Peptidylglycine α-amidating monooxygenase (PAM) catalyzes a two-step reaction resulting in the C-terminal amidation of peptides, a process important for their stability and biological activity. Here we show that in human, mouse, and insect cells, peptide amidation is exquisitely sensitive to hypoxia. Different amidation events on chromogranin A, and on peptides processed from proopiomelanocortin, manifest similar striking sensitivity to hypoxia in a range of neuroendocrine cells, being progressively inhibited from mild (7% O2) to severe (1% O2) hypoxia. In developing Drosophila melanogaster larvae, FMRF amidation in thoracic ventral (Tv) neurons is strikingly suppressed by hypoxia. Our findings have thus defined a novel monooxygenase-based oxygen sensing mechanism that has the capacity to signal changes in oxygen availability to peptidergic pathways.
Fil: Simpson, Peter D.. University Of Oxford; Reino Unido
Fil: Eipper, Betty A.. University Of Connecticut; Estados Unidos
Fil: Katz, Maximiliano Javier. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
Fil: Gándara, Lautaro. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
Fil: Wappner, Pablo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
Fil: Fischer, Roman. University Of Oxford; Reino Unido
Fil: Hodson, Emma J.. University Of Oxford; Reino Unido
Fil: Ratcliffe, Peter J.. University Of Oxford; Reino Unido
Fil: Masson, Norma. University Of Oxford; Reino Unido
description Interactions between biological pathways and molecular oxygen require robust mechanisms for detecting and responding to changes in cellular oxygen availability, to support oxygen homeostasis. Peptidylglycine α-amidating monooxygenase (PAM) catalyzes a two-step reaction resulting in the C-terminal amidation of peptides, a process important for their stability and biological activity. Here we show that in human, mouse, and insect cells, peptide amidation is exquisitely sensitive to hypoxia. Different amidation events on chromogranin A, and on peptides processed from proopiomelanocortin, manifest similar striking sensitivity to hypoxia in a range of neuroendocrine cells, being progressively inhibited from mild (7% O2) to severe (1% O2) hypoxia. In developing Drosophila melanogaster larvae, FMRF amidation in thoracic ventral (Tv) neurons is strikingly suppressed by hypoxia. Our findings have thus defined a novel monooxygenase-based oxygen sensing mechanism that has the capacity to signal changes in oxygen availability to peptidergic pathways.
publishDate 2015
dc.date.none.fl_str_mv 2015-10
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/11336/9757
Simpson, Peter D.; Eipper, Betty A.; Katz, Maximiliano Javier; Gándara, Lautaro; Wappner, Pablo; et al.; Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cell; American Society For Biochemistry And Molecular Biology; Journal Of Biological Chemistry; 290; 41; 10-2015; 24891-24901
0021-9258
url http://hdl.handle.net/11336/9757
identifier_str_mv Simpson, Peter D.; Eipper, Betty A.; Katz, Maximiliano Javier; Gándara, Lautaro; Wappner, Pablo; et al.; Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cell; American Society For Biochemistry And Molecular Biology; Journal Of Biological Chemistry; 290; 41; 10-2015; 24891-24901
0021-9258
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/290/41/24891.long
info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M115.667246
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society For Biochemistry And Molecular Biology
publisher.none.fl_str_mv American Society For Biochemistry And Molecular Biology
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_ 1846083067034206208
score 13.22299

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