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 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.
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2016
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Subjects: | CALCIO, OXIGENO, ADAPTACION, PROTEINAS, CORAZON, |
Online Access: | https://repositorio.uca.edu.ar/handle/123456789/8758 |
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oai:ucacris:123456789-87582019-09-18T04:14:09Z TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling 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 CALCIO OXIGENO ADAPTACION PROTEINAS CORAZON 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. 2019-09-17T21:19:09Z 2019-09-17T21:19:09Z 2016 Artículo Kitajima N, Numaga-Tomita T, Watanabe M, et al. TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling. Scientific Reports. 2016;6:37001. doi:10.1038/srep37001 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8758 2045-2322 https://repositorio.uca.edu.ar/handle/123456789/8758 10.1038/srep37001 27833156 eng Acceso Abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Scientific Reports. 2016;6:37001 |
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CALCIO OXIGENO ADAPTACION PROTEINAS CORAZON CALCIO OXIGENO ADAPTACION PROTEINAS CORAZON |
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CALCIO OXIGENO ADAPTACION PROTEINAS CORAZON 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 |
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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 |
topic_facet |
CALCIO OXIGENO ADAPTACION PROTEINAS CORAZON |
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 |
2016 |
url |
https://repositorio.uca.edu.ar/handle/123456789/8758 |
work_keys_str_mv |
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1756275846275923968 |