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

Autores
Oda, Sayaka; Numaga-Tomita, Takuro; Kitajima, Naoyuki; Toyama, 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
Fil: Oda, Sayaka. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Oda, Sayaka. The Graduate University for Advanced Studies. Department of Physiological Sciences; Japón
Fil: Numaga-Tomita, Takuro. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Numaga-Tomita, Takuro. The Graduate University for Advanced Studies. Department of Physiological Sciences; Japón
Fil: Kitajima, Naoyuki. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Kitajima, Naoyuki. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón
Fil: Toyama, Takashi. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Toyama, Takashi. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón
Fil: Toyama, Takashi. University of Tsukuba. Faculty of Medicine and Graduate School of Comprehensive Human Sciences. Environmental Biology Laboratory; Japón
Fil: Harada, Eri. Ajinomoto Company Incorporated; Japón
Fil: Harada, Eri. EA Pharma Company; Japón
Fil: Shimauchi, Tsukasa. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Shimauchi, Tsukasa. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón
Fil: Nishimura, Akiyuki. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Nishimura, Akiyuki. The Graduate University for Advanced Studies. Department of Physiological Sciences; Japón
Fil: Ishikawa, Tatsuya. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Ishikawa, Tatsuya. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón
Fil: Ishikawa, Tatsuya. EA Pharma Company; Japón
Fil: Kumagai, Yoshito. University of Tsukuba. Faculty of Medicine and Graduate School of Comprehensive Human Sciences. Environmental Biology Laboratory; Japón
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Laboratory of Neuroscience; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Nishida, Motohiro. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Nishida, Motohiro. The Graduate University for Advanced Studies. Department of Physiological Sciences; Japón
Fil: Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón
Abstract: 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.
Fuente
Scientific Reports. 2017;7(1):1-14
Materia
HIPERGLUCEMIA
FIBROSIS
CORAZON
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
Repositorio Institucional (UCA)
Institución
Pontificia Universidad Católica Argentina
OAI Identificador
oai:ucacris:123456789/8722
Acceder
id RIUCA_3b8cfbc9922c91f096f05b8b9b6465b4
oai_identifier_str oai:ucacris:123456789/8722
network_acronym_str RIUCA
repository_id_str 2585
network_name_str Repositorio Institucional (UCA)
spelling TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in miceOda, SayakaNumaga-Tomita, TakuroKitajima, NaoyukiToyama, TakashiHarada, EriShimauchi, TsukasaNishimura, AkiyukiIshikawa, TatsuyaKumagai, YoshitoBirnbaumer, LutzNishida, MotohiroHIPERGLUCEMIAFIBROSISCORAZONFil: Oda, Sayaka. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; JapónFil: Oda, Sayaka. The Graduate University for Advanced Studies. Department of Physiological Sciences; JapónFil: Numaga-Tomita, Takuro. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; JapónFil: Numaga-Tomita, Takuro. The Graduate University for Advanced Studies. Department of Physiological Sciences; JapónFil: Kitajima, Naoyuki. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; JapónFil: Kitajima, Naoyuki. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; JapónFil: Toyama, Takashi. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; JapónFil: Toyama, Takashi. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; JapónFil: Toyama, Takashi. University of Tsukuba. Faculty of Medicine and Graduate School of Comprehensive Human Sciences. Environmental Biology Laboratory; JapónFil: Harada, Eri. Ajinomoto Company Incorporated; JapónFil: Harada, Eri. EA Pharma Company; JapónFil: Shimauchi, Tsukasa. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; JapónFil: Shimauchi, Tsukasa. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; JapónFil: Nishimura, Akiyuki. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; JapónFil: Nishimura, Akiyuki. The Graduate University for Advanced Studies. Department of Physiological Sciences; JapónFil: Ishikawa, Tatsuya. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; JapónFil: Ishikawa, Tatsuya. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; JapónFil: Ishikawa, Tatsuya. EA Pharma Company; JapónFil: Kumagai, Yoshito. University of Tsukuba. Faculty of Medicine and Graduate School of Comprehensive Human Sciences. Environmental Biology Laboratory; JapónFil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Laboratory of Neuroscience; Estados UnidosFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Nishida, Motohiro. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; JapónFil: Nishida, Motohiro. The Graduate University for Advanced Studies. Department of Physiological Sciences; JapónFil: Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; JapónAbstract: 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.Nature Research2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/87222045-232210.1038/s41598-017-07903-428790356Oda S, Numaga-Tomita T, Kitajima N, et al. TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice [en línea]. Scientific Reports. 2017;7(1):1-14. doi:10.1038/s41598-017-07903-4 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8722Scientific Reports. 2017;7(1):1-14reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:56:54Zoai:ucacris:123456789/8722instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:56:55.115Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse
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
HIPERGLUCEMIA
FIBROSIS
CORAZON
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
Toyama, 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
Toyama, Takashi
Harada, Eri
Shimauchi, Tsukasa
Nishimura, Akiyuki
Ishikawa, Tatsuya
Kumagai, Yoshito
Birnbaumer, Lutz
Nishida, Motohiro
author_role author
author2 Numaga-Tomita, Takuro
Kitajima, Naoyuki
Toyama, 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 HIPERGLUCEMIA
FIBROSIS
CORAZON
topic HIPERGLUCEMIA
FIBROSIS
CORAZON
dc.description.none.fl_txt_mv Fil: Oda, Sayaka. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Oda, Sayaka. The Graduate University for Advanced Studies. Department of Physiological Sciences; Japón
Fil: Numaga-Tomita, Takuro. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Numaga-Tomita, Takuro. The Graduate University for Advanced Studies. Department of Physiological Sciences; Japón
Fil: Kitajima, Naoyuki. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Kitajima, Naoyuki. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón
Fil: Toyama, Takashi. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Toyama, Takashi. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón
Fil: Toyama, Takashi. University of Tsukuba. Faculty of Medicine and Graduate School of Comprehensive Human Sciences. Environmental Biology Laboratory; Japón
Fil: Harada, Eri. Ajinomoto Company Incorporated; Japón
Fil: Harada, Eri. EA Pharma Company; Japón
Fil: Shimauchi, Tsukasa. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Shimauchi, Tsukasa. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón
Fil: Nishimura, Akiyuki. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Nishimura, Akiyuki. The Graduate University for Advanced Studies. Department of Physiological Sciences; Japón
Fil: Ishikawa, Tatsuya. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Ishikawa, Tatsuya. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón
Fil: Ishikawa, Tatsuya. EA Pharma Company; Japón
Fil: Kumagai, Yoshito. University of Tsukuba. Faculty of Medicine and Graduate School of Comprehensive Human Sciences. Environmental Biology Laboratory; Japón
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Laboratory of Neuroscience; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Nishida, Motohiro. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
Fil: Nishida, Motohiro. The Graduate University for Advanced Studies. Department of Physiological Sciences; Japón
Fil: Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón
Abstract: 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.
description Fil: Oda, Sayaka. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón
publishDate 2017
dc.date.none.fl_str_mv 2017
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 https://repositorio.uca.edu.ar/handle/123456789/8722
2045-2322
10.1038/s41598-017-07903-4
28790356
Oda S, Numaga-Tomita T, Kitajima N, et al. TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice [en línea]. Scientific Reports. 2017;7(1):1-14. doi:10.1038/s41598-017-07903-4 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8722
url https://repositorio.uca.edu.ar/handle/123456789/8722
identifier_str_mv 2045-2322
10.1038/s41598-017-07903-4
28790356
Oda S, Numaga-Tomita T, Kitajima N, et al. TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice [en línea]. Scientific Reports. 2017;7(1):1-14. doi:10.1038/s41598-017-07903-4 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8722
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv Scientific Reports. 2017;7(1):1-14
reponame:Repositorio Institucional (UCA)
instname:Pontificia Universidad Católica Argentina
reponame_str Repositorio Institucional (UCA)
collection Repositorio Institucional (UCA)
instname_str Pontificia Universidad Católica Argentina
repository.name.fl_str_mv Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina
repository.mail.fl_str_mv claudia_fernandez@uca.edu.ar
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score 13.070432

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