TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling

Abstract: 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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Artículo
Lenguaje:Inglés
Publicado: 2019
Materias:
CALCIO
OXIGENO
ADAPTACION
PROTEINAS
CORAZON
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8758
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8758
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic CALCIO
OXIGENO
ADAPTACION
PROTEINAS
CORAZON
spellingShingle CALCIO
OXIGENO
ADAPTACION
PROTEINAS
CORAZON
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
TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling
topic_facet CALCIO
OXIGENO
ADAPTACION
PROTEINAS
CORAZON
description Abstract: 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 Ca2+-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 Ca2+-dependent Nox2 activation through TRPC3-mediated background Ca2+ 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 Ca2+ influx. The novel TRPC3 function as a PRROS provides a mechanistic explanation for how diastolic Ca2+ influx specifically encodes signals to induce ROS-mediated maladaptive remodeling and offers new therapeutic possibilities.
format Artículo
author 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_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_sort Kitajima, Naoyuki
title TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling
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
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8758
work_keys_str_mv AT kitajimanaoyuki trpc3positivelyregulatesreactiveoxygenspeciesdrivingmaladaptivecardiacremodeling
AT numagatomitatakuro trpc3positivelyregulatesreactiveoxygenspeciesdrivingmaladaptivecardiacremodeling
AT watanabemasahiko trpc3positivelyregulatesreactiveoxygenspeciesdrivingmaladaptivecardiacremodeling
AT kurodatakuya trpc3positivelyregulatesreactiveoxygenspeciesdrivingmaladaptivecardiacremodeling
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AT idetomomi trpc3positivelyregulatesreactiveoxygenspeciesdrivingmaladaptivecardiacremodeling
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bdutipo_str Repositorios
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