TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice

Autores
Oda, Sayaka; Numaga Tomita, Takuro; Kitajima, Naoyuki; Tomizaki, Takashi; Harada, Eri; Shimauchi, Tsukasa; Nishimura, Akiyuki; Ishikawa, Tatsuya; Kumagai, Yoshito; Birnbaumer, Lutz; Nishida, Motohiro
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure. We here demonstrated that deletion of TRPC6 had no impact on pressure overload-induced heart failure despite inhibiting interstitial fibrosis in mice. TRPC6-deficient mouse hearts 1 week after transverse aortic constriction showed comparable increases in fibrotic gene expressions and ROS production but promoted inductions of inflammatory cytokines, compared to wild type hearts. Treatment of TRPC6-deficient mice with streptozotocin caused severe reduction of cardiac contractility with enhancing urinary and cardiac lipid peroxide levels, compared to wild type and TRPC3-deficient mice. Knockdown of TRPC6, but not TRPC3, enhanced basal expression levels of cytokines in rat cardiomyocytes. TRPC6 could interact with Nox2, but the abundance of TRPC6 was inversely correlated with that of Nox2. These results strongly suggest that Nox2 destabilization through disrupting TRPC3-Nox2 complex underlies attenuation of hyperglycemia-induced heart failure by TRPC6.
Fil: Oda, Sayaka. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón
Fil: Numaga Tomita, Takuro. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón
Fil: Kitajima, Naoyuki. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; Japón
Fil: Tomizaki, Takashi. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; Japón. University of Tsukuba; Japón
Fil: Harada, Eri. Ajinomoto Co.; Japón. EA Pharma Co.; Japón
Fil: Shimauchi, Tsukasa. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; Japón
Fil: Nishimura, Akiyuki. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón. Ajinomoto Co.; Japón
Fil: Ishikawa, Tatsuya. Kyushu University; Japón. Ajinomoto Co.; Japón. EA Pharma Co.; Japón
Fil: Kumagai, Yoshito. University of Tsukuba; 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
Fil: Nishida, Motohiro. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón. Kyushu University; Japón. PRESTO; Japón
Materia
TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice
TRPC3-Nox2
TRPC6
hyperglycemia
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:11336/48809
Acceder
id CONICETDig_80f2a995a1ebbd8162b28c42547f8055
oai_identifier_str oai:ri.conicet.gov.ar:11336/48809
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in miceOda, SayakaNumaga Tomita, TakuroKitajima, NaoyukiTomizaki, TakashiHarada, EriShimauchi, TsukasaNishimura, AkiyukiIshikawa, TatsuyaKumagai, YoshitoBirnbaumer, LutzNishida, MotohiroTRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in miceTRPC3-Nox2TRPC6hyperglycemiahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure. We here demonstrated that deletion of TRPC6 had no impact on pressure overload-induced heart failure despite inhibiting interstitial fibrosis in mice. TRPC6-deficient mouse hearts 1 week after transverse aortic constriction showed comparable increases in fibrotic gene expressions and ROS production but promoted inductions of inflammatory cytokines, compared to wild type hearts. Treatment of TRPC6-deficient mice with streptozotocin caused severe reduction of cardiac contractility with enhancing urinary and cardiac lipid peroxide levels, compared to wild type and TRPC3-deficient mice. Knockdown of TRPC6, but not TRPC3, enhanced basal expression levels of cytokines in rat cardiomyocytes. TRPC6 could interact with Nox2, but the abundance of TRPC6 was inversely correlated with that of Nox2. These results strongly suggest that Nox2 destabilization through disrupting TRPC3-Nox2 complex underlies attenuation of hyperglycemia-induced heart failure by TRPC6.Fil: Oda, Sayaka. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; JapónFil: Numaga Tomita, Takuro. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; JapónFil: Kitajima, Naoyuki. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; JapónFil: Tomizaki, Takashi. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; Japón. University of Tsukuba; JapónFil: Harada, Eri. Ajinomoto Co.; Japón. EA Pharma Co.; JapónFil: Shimauchi, Tsukasa. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; JapónFil: Nishimura, Akiyuki. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón. Ajinomoto Co.; JapónFil: Ishikawa, Tatsuya. Kyushu University; Japón. Ajinomoto Co.; Japón. EA Pharma Co.; JapónFil: Kumagai, Yoshito. University of Tsukuba; 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; ArgentinaFil: Nishida, Motohiro. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón. Kyushu University; Japón. PRESTO; JapónSci Rep2017-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/48809Oda, Sayaka; Numaga Tomita, Takuro; Kitajima, Naoyuki; Tomizaki, Takashi; Harada, Eri; et al.; TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice; Sci Rep; Scientific Reports; 7; 1; 8-2017; 1-142045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-017-07903-4info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-07903-4info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T10:44:11Zoai:ri.conicet.gov.ar:11336/48809instacron: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:34982025-09-17 10:44:11.809CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice
title TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice
spellingShingle TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice
Oda, Sayaka
TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice
TRPC3-Nox2
TRPC6
hyperglycemia
title_short TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice
title_full TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice
title_fullStr TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice
title_full_unstemmed TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice
title_sort TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice
dc.creator.none.fl_str_mv Oda, Sayaka
Numaga Tomita, Takuro
Kitajima, Naoyuki
Tomizaki, Takashi
Harada, Eri
Shimauchi, Tsukasa
Nishimura, Akiyuki
Ishikawa, Tatsuya
Kumagai, Yoshito
Birnbaumer, Lutz
Nishida, Motohiro
author Oda, Sayaka
author_facet Oda, Sayaka
Numaga Tomita, Takuro
Kitajima, Naoyuki
Tomizaki, Takashi
Harada, Eri
Shimauchi, Tsukasa
Nishimura, Akiyuki
Ishikawa, Tatsuya
Kumagai, Yoshito
Birnbaumer, Lutz
Nishida, Motohiro
author_role author
author2 Numaga Tomita, Takuro
Kitajima, Naoyuki
Tomizaki, Takashi
Harada, Eri
Shimauchi, Tsukasa
Nishimura, Akiyuki
Ishikawa, Tatsuya
Kumagai, Yoshito
Birnbaumer, Lutz
Nishida, Motohiro
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice
TRPC3-Nox2
TRPC6
hyperglycemia
topic TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice
TRPC3-Nox2
TRPC6
hyperglycemia
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure. We here demonstrated that deletion of TRPC6 had no impact on pressure overload-induced heart failure despite inhibiting interstitial fibrosis in mice. TRPC6-deficient mouse hearts 1 week after transverse aortic constriction showed comparable increases in fibrotic gene expressions and ROS production but promoted inductions of inflammatory cytokines, compared to wild type hearts. Treatment of TRPC6-deficient mice with streptozotocin caused severe reduction of cardiac contractility with enhancing urinary and cardiac lipid peroxide levels, compared to wild type and TRPC3-deficient mice. Knockdown of TRPC6, but not TRPC3, enhanced basal expression levels of cytokines in rat cardiomyocytes. TRPC6 could interact with Nox2, but the abundance of TRPC6 was inversely correlated with that of Nox2. These results strongly suggest that Nox2 destabilization through disrupting TRPC3-Nox2 complex underlies attenuation of hyperglycemia-induced heart failure by TRPC6.
Fil: Oda, Sayaka. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón
Fil: Numaga Tomita, Takuro. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón
Fil: Kitajima, Naoyuki. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; Japón
Fil: Tomizaki, Takashi. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; Japón. University of Tsukuba; Japón
Fil: Harada, Eri. Ajinomoto Co.; Japón. EA Pharma Co.; Japón
Fil: Shimauchi, Tsukasa. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; Japón
Fil: Nishimura, Akiyuki. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón. Ajinomoto Co.; Japón
Fil: Ishikawa, Tatsuya. Kyushu University; Japón. Ajinomoto Co.; Japón. EA Pharma Co.; Japón
Fil: Kumagai, Yoshito. University of Tsukuba; 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
Fil: Nishida, Motohiro. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón. Kyushu University; Japón. PRESTO; Japón
description Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure. We here demonstrated that deletion of TRPC6 had no impact on pressure overload-induced heart failure despite inhibiting interstitial fibrosis in mice. TRPC6-deficient mouse hearts 1 week after transverse aortic constriction showed comparable increases in fibrotic gene expressions and ROS production but promoted inductions of inflammatory cytokines, compared to wild type hearts. Treatment of TRPC6-deficient mice with streptozotocin caused severe reduction of cardiac contractility with enhancing urinary and cardiac lipid peroxide levels, compared to wild type and TRPC3-deficient mice. Knockdown of TRPC6, but not TRPC3, enhanced basal expression levels of cytokines in rat cardiomyocytes. TRPC6 could interact with Nox2, but the abundance of TRPC6 was inversely correlated with that of Nox2. These results strongly suggest that Nox2 destabilization through disrupting TRPC3-Nox2 complex underlies attenuation of hyperglycemia-induced heart failure by TRPC6.
publishDate 2017
dc.date.none.fl_str_mv 2017-08
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/11336/48809
Oda, Sayaka; Numaga Tomita, Takuro; Kitajima, Naoyuki; Tomizaki, Takashi; Harada, Eri; et al.; TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice; Sci Rep; Scientific Reports; 7; 1; 8-2017; 1-14
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/48809
identifier_str_mv Oda, Sayaka; Numaga Tomita, Takuro; Kitajima, Naoyuki; Tomizaki, Takashi; Harada, Eri; et al.; TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice; Sci Rep; Scientific Reports; 7; 1; 8-2017; 1-14
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/url/https://www.nature.com/articles/s41598-017-07903-4
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-07903-4
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 Sci Rep
publisher.none.fl_str_mv Sci Rep
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 13.001348

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