TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling

Autores
Kitajima, Naoyuki; Numaga Tomita, Takuro; Watanabe, Masahiko; Kuroda, Takuya; Nishimura, Akiyuki; Miyano, Kei; Yasuda, Satoshi; Kuwahara, Koichiro; Sato, Yoji; Ide, Tomomi; Birnbaumer, Lutz; Sumimoto, Hideki; Mori, Yasuo; Nishida, Motohiro
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Reactive oxygen species (ROS) produced by NADPH oxidase 2 (Nox2) function as key mediators of mechanotransduction during both physiological adaptation to mechanical load and maladaptive remodeling of the heart. This is despite low levels of cardiac Nox2 expression. The mechanism underlying the transition from adaptation to maladaptation remains obscure, however. We demonstrate that transient receptor potential canonical 3 (TRPC3), a Ca 2+-permeable channel, acts as a positive regulator of ROS (PRROS) in cardiomyocytes, and specifically regulates pressure overload-induced maladaptive cardiac remodeling in mice. TRPC3 physically interacts with Nox2 at specific C-terminal sites, thereby protecting Nox2 from proteasome-dependent degradation and amplifying Ca 2+-dependent Nox2 activation through TRPC3-mediated background Ca 2+ entry. Nox2 also stabilizes TRPC3 proteins to enhance TRPC3 channel activity. Expression of TRPC3 C-terminal polypeptide abolished TRPC3-regulated ROS production by disrupting TRPC3-Nox2 interaction, without affecting TRPC3-mediated Ca 2+ influx. The novel TRPC3 function as a PRROS provides a mechanistic explanation for how diastolic Ca 2+ influx specifically encodes signals to induce ROS-mediated maladaptive remodeling and offers new therapeutic possibilities.
Fil: Kitajima, Naoyuki. National Institutes of Natural Sciences; Japón. Kyushu University; Japón
Fil: Numaga Tomita, Takuro. National Institutes of Natural Sciences; Japón. University for Advanced Studies; Japón
Fil: Watanabe, Masahiko. Hokkaido University School of Medicine; Japón
Fil: Kuroda, Takuya. National Institutes of Natural Sciences; Japón
Fil: Nishimura, Akiyuki. National Institutes of Natural Sciences; Japón. University for Advanced Studies; Japón
Fil: Miyano, Kei. Kyushu University Graduate School of Medical Sciences; Japón
Fil: Yasuda, Satoshi. National Institute of Health Sciences; Japón
Fil: Kuwahara, Koichiro. Kyoto University Graduate School of Medicine; Japón
Fil: Sato, Yoji. Kyushu University; Japón. National Institute of Health Sciences; Japón
Fil: Ide, Tomomi. Kyushu University; Japón
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Research Triangle Park; Estados Unidos
Fil: Sumimoto, Hideki. Kyushu University Graduate School of Medical Sciences; Japón
Fil: Mori, Yasuo. Kyoto University; Japón
Fil: Nishida, Motohiro. National Institutes of Natural Sciences; Japón. Kyushu University; Japón. University for Advanced Studies; Japón. PRESTO; Japón
Materia
TRPC3
Nox2
ROS
Cardiac maladaprtive Fibrosis
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:11336/53918
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/53918
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodelingKitajima, NaoyukiNumaga Tomita, TakuroWatanabe, MasahikoKuroda, TakuyaNishimura, AkiyukiMiyano, KeiYasuda, SatoshiKuwahara, KoichiroSato, YojiIde, TomomiBirnbaumer, LutzSumimoto, HidekiMori, YasuoNishida, MotohiroTRPC3Nox2ROSCardiac maladaprtive Fibrosishttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Reactive oxygen species (ROS) produced by NADPH oxidase 2 (Nox2) function as key mediators of mechanotransduction during both physiological adaptation to mechanical load and maladaptive remodeling of the heart. This is despite low levels of cardiac Nox2 expression. The mechanism underlying the transition from adaptation to maladaptation remains obscure, however. We demonstrate that transient receptor potential canonical 3 (TRPC3), a Ca 2+-permeable channel, acts as a positive regulator of ROS (PRROS) in cardiomyocytes, and specifically regulates pressure overload-induced maladaptive cardiac remodeling in mice. TRPC3 physically interacts with Nox2 at specific C-terminal sites, thereby protecting Nox2 from proteasome-dependent degradation and amplifying Ca 2+-dependent Nox2 activation through TRPC3-mediated background Ca 2+ entry. Nox2 also stabilizes TRPC3 proteins to enhance TRPC3 channel activity. Expression of TRPC3 C-terminal polypeptide abolished TRPC3-regulated ROS production by disrupting TRPC3-Nox2 interaction, without affecting TRPC3-mediated Ca 2+ influx. The novel TRPC3 function as a PRROS provides a mechanistic explanation for how diastolic Ca 2+ influx specifically encodes signals to induce ROS-mediated maladaptive remodeling and offers new therapeutic possibilities.Fil: Kitajima, Naoyuki. National Institutes of Natural Sciences; Japón. Kyushu University; JapónFil: Numaga Tomita, Takuro. National Institutes of Natural Sciences; Japón. University for Advanced Studies; JapónFil: Watanabe, Masahiko. Hokkaido University School of Medicine; JapónFil: Kuroda, Takuya. National Institutes of Natural Sciences; JapónFil: Nishimura, Akiyuki. National Institutes of Natural Sciences; Japón. University for Advanced Studies; JapónFil: Miyano, Kei. Kyushu University Graduate School of Medical Sciences; JapónFil: Yasuda, Satoshi. National Institute of Health Sciences; JapónFil: Kuwahara, Koichiro. Kyoto University Graduate School of Medicine; JapónFil: Sato, Yoji. Kyushu University; Japón. National Institute of Health Sciences; JapónFil: Ide, Tomomi. Kyushu University; JapónFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Research Triangle Park; Estados UnidosFil: Sumimoto, Hideki. Kyushu University Graduate School of Medical Sciences; JapónFil: Mori, Yasuo. Kyoto University; JapónFil: Nishida, Motohiro. National Institutes of Natural Sciences; Japón. Kyushu University; Japón. University for Advanced Studies; Japón. PRESTO; JapónNature Publishing Group2016-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/53918Kitajima, Naoyuki; Numaga Tomita, Takuro; Watanabe, Masahiko; Kuroda, Takuya; Nishimura, Akiyuki; et al.; TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling; Nature Publishing Group; Scientific Reports; 6; 11-2016; 1-172045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/srep37001info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/srep37001info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:24:19Zoai:ri.conicet.gov.ar:11336/53918instacron: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 14:24:19.892CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling
title TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling
spellingShingle TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling
Kitajima, Naoyuki
TRPC3
Nox2
ROS
Cardiac maladaprtive Fibrosis
title_short TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling
title_full TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling
title_fullStr TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling
title_full_unstemmed TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling
title_sort TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling
dc.creator.none.fl_str_mv Kitajima, Naoyuki
Numaga Tomita, Takuro
Watanabe, Masahiko
Kuroda, Takuya
Nishimura, Akiyuki
Miyano, Kei
Yasuda, Satoshi
Kuwahara, Koichiro
Sato, Yoji
Ide, Tomomi
Birnbaumer, Lutz
Sumimoto, Hideki
Mori, Yasuo
Nishida, Motohiro
author Kitajima, Naoyuki
author_facet Kitajima, Naoyuki
Numaga Tomita, Takuro
Watanabe, Masahiko
Kuroda, Takuya
Nishimura, Akiyuki
Miyano, Kei
Yasuda, Satoshi
Kuwahara, Koichiro
Sato, Yoji
Ide, Tomomi
Birnbaumer, Lutz
Sumimoto, Hideki
Mori, Yasuo
Nishida, Motohiro
author_role author
author2 Numaga Tomita, Takuro
Watanabe, Masahiko
Kuroda, Takuya
Nishimura, Akiyuki
Miyano, Kei
Yasuda, Satoshi
Kuwahara, Koichiro
Sato, Yoji
Ide, Tomomi
Birnbaumer, Lutz
Sumimoto, Hideki
Mori, Yasuo
Nishida, Motohiro
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TRPC3
Nox2
ROS
Cardiac maladaprtive Fibrosis
topic TRPC3
Nox2
ROS
Cardiac maladaprtive Fibrosis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Reactive oxygen species (ROS) produced by NADPH oxidase 2 (Nox2) function as key mediators of mechanotransduction during both physiological adaptation to mechanical load and maladaptive remodeling of the heart. This is despite low levels of cardiac Nox2 expression. The mechanism underlying the transition from adaptation to maladaptation remains obscure, however. We demonstrate that transient receptor potential canonical 3 (TRPC3), a Ca 2+-permeable channel, acts as a positive regulator of ROS (PRROS) in cardiomyocytes, and specifically regulates pressure overload-induced maladaptive cardiac remodeling in mice. TRPC3 physically interacts with Nox2 at specific C-terminal sites, thereby protecting Nox2 from proteasome-dependent degradation and amplifying Ca 2+-dependent Nox2 activation through TRPC3-mediated background Ca 2+ entry. Nox2 also stabilizes TRPC3 proteins to enhance TRPC3 channel activity. Expression of TRPC3 C-terminal polypeptide abolished TRPC3-regulated ROS production by disrupting TRPC3-Nox2 interaction, without affecting TRPC3-mediated Ca 2+ influx. The novel TRPC3 function as a PRROS provides a mechanistic explanation for how diastolic Ca 2+ influx specifically encodes signals to induce ROS-mediated maladaptive remodeling and offers new therapeutic possibilities.
Fil: Kitajima, Naoyuki. National Institutes of Natural Sciences; Japón. Kyushu University; Japón
Fil: Numaga Tomita, Takuro. National Institutes of Natural Sciences; Japón. University for Advanced Studies; Japón
Fil: Watanabe, Masahiko. Hokkaido University School of Medicine; Japón
Fil: Kuroda, Takuya. National Institutes of Natural Sciences; Japón
Fil: Nishimura, Akiyuki. National Institutes of Natural Sciences; Japón. University for Advanced Studies; Japón
Fil: Miyano, Kei. Kyushu University Graduate School of Medical Sciences; Japón
Fil: Yasuda, Satoshi. National Institute of Health Sciences; Japón
Fil: Kuwahara, Koichiro. Kyoto University Graduate School of Medicine; Japón
Fil: Sato, Yoji. Kyushu University; Japón. National Institute of Health Sciences; Japón
Fil: Ide, Tomomi. Kyushu University; Japón
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Research Triangle Park; Estados Unidos
Fil: Sumimoto, Hideki. Kyushu University Graduate School of Medical Sciences; Japón
Fil: Mori, Yasuo. Kyoto University; Japón
Fil: Nishida, Motohiro. National Institutes of Natural Sciences; Japón. Kyushu University; Japón. University for Advanced Studies; Japón. PRESTO; Japón
description Reactive oxygen species (ROS) produced by NADPH oxidase 2 (Nox2) function as key mediators of mechanotransduction during both physiological adaptation to mechanical load and maladaptive remodeling of the heart. This is despite low levels of cardiac Nox2 expression. The mechanism underlying the transition from adaptation to maladaptation remains obscure, however. We demonstrate that transient receptor potential canonical 3 (TRPC3), a Ca 2+-permeable channel, acts as a positive regulator of ROS (PRROS) in cardiomyocytes, and specifically regulates pressure overload-induced maladaptive cardiac remodeling in mice. TRPC3 physically interacts with Nox2 at specific C-terminal sites, thereby protecting Nox2 from proteasome-dependent degradation and amplifying Ca 2+-dependent Nox2 activation through TRPC3-mediated background Ca 2+ entry. Nox2 also stabilizes TRPC3 proteins to enhance TRPC3 channel activity. Expression of TRPC3 C-terminal polypeptide abolished TRPC3-regulated ROS production by disrupting TRPC3-Nox2 interaction, without affecting TRPC3-mediated Ca 2+ influx. The novel TRPC3 function as a PRROS provides a mechanistic explanation for how diastolic Ca 2+ influx specifically encodes signals to induce ROS-mediated maladaptive remodeling and offers new therapeutic possibilities.
publishDate 2016
dc.date.none.fl_str_mv 2016-11
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/11336/53918
Kitajima, Naoyuki; Numaga Tomita, Takuro; Watanabe, Masahiko; Kuroda, Takuya; Nishimura, Akiyuki; et al.; TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling; Nature Publishing Group; Scientific Reports; 6; 11-2016; 1-17
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/53918
identifier_str_mv Kitajima, Naoyuki; Numaga Tomita, Takuro; Watanabe, Masahiko; Kuroda, Takuya; Nishimura, Akiyuki; et al.; TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling; Nature Publishing Group; Scientific Reports; 6; 11-2016; 1-17
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/srep37001
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/srep37001
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
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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
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score 13.22299

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