TRPC3-Nox2 axis mediates nutritional deficiency-induced cardiomyocyte atrophy

Suhaini Binti Sudi, Tomohiro Tanaka, Sayaka Oda, Kazuhiro Nishiyama, Akiyuki Nishimura, Caroline Sunggip, Supachoke Mangmool, Takuro Numaga-Tomita, Motohiro Nishida

Research output: Contribution to journalArticle

Abstract

Myocardial atrophy, characterized by the decreases in size and contractility of cardiomyocytes, is caused by severe malnutrition and/or mechanical unloading. Extracellular adenosine 5′-triphosphate (ATP), known as a danger signal, is recognized to negatively regulate cell volume. However, it is obscure whether extracellular ATP contributes to cardiomyocyte atrophy. Here, we report that ATP induces atrophy of neonatal rat cardiomyocytes (NRCMs) without cell death through P2Y2 receptors. ATP led to overproduction of reactive oxygen species (ROS) through increased amount of NADPH oxidase (Nox) 2 proteins, due to increased physical interaction between Nox2 and canonical transient receptor potential 3 (TRPC3). This ATP-mediated formation of TRPC3-Nox2 complex was also pathophysiologically involved in nutritional deficiency-induced NRCM atrophy. Strikingly, knockdown of either TRPC3 or Nox2 suppressed nutritional deficiency-induced ATP release, as well as ROS production and NRCM atrophy. Taken together, we propose that TRPC3-Nox2 axis, activated by extracellular ATP, is the key component that mediates nutritional deficiency-induced cardiomyocyte atrophy.

Original languageEnglish
Article number9785
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

Fingerprint

Cardiac Myocytes
Malnutrition
Atrophy
Adenosine Triphosphate
Reactive Oxygen Species
Purinergic P2Y2 Receptors
NADPH Oxidase
Cell Size
Cell Death
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

TRPC3-Nox2 axis mediates nutritional deficiency-induced cardiomyocyte atrophy. / Sudi, Suhaini Binti; Tanaka, Tomohiro; Oda, Sayaka; Nishiyama, Kazuhiro; Nishimura, Akiyuki; Sunggip, Caroline; Mangmool, Supachoke; Numaga-Tomita, Takuro; Nishida, Motohiro.

In: Scientific reports, Vol. 9, No. 1, 9785, 01.12.2019.

Research output: Contribution to journalArticle

Sudi, SB, Tanaka, T, Oda, S, Nishiyama, K, Nishimura, A, Sunggip, C, Mangmool, S, Numaga-Tomita, T & Nishida, M 2019, 'TRPC3-Nox2 axis mediates nutritional deficiency-induced cardiomyocyte atrophy', Scientific reports, vol. 9, no. 1, 9785. https://doi.org/10.1038/s41598-019-46252-2
Sudi, Suhaini Binti ; Tanaka, Tomohiro ; Oda, Sayaka ; Nishiyama, Kazuhiro ; Nishimura, Akiyuki ; Sunggip, Caroline ; Mangmool, Supachoke ; Numaga-Tomita, Takuro ; Nishida, Motohiro. / TRPC3-Nox2 axis mediates nutritional deficiency-induced cardiomyocyte atrophy. In: Scientific reports. 2019 ; Vol. 9, No. 1.
@article{2aebd4ca237742b2afd600160c2d18fa,
title = "TRPC3-Nox2 axis mediates nutritional deficiency-induced cardiomyocyte atrophy",
abstract = "Myocardial atrophy, characterized by the decreases in size and contractility of cardiomyocytes, is caused by severe malnutrition and/or mechanical unloading. Extracellular adenosine 5′-triphosphate (ATP), known as a danger signal, is recognized to negatively regulate cell volume. However, it is obscure whether extracellular ATP contributes to cardiomyocyte atrophy. Here, we report that ATP induces atrophy of neonatal rat cardiomyocytes (NRCMs) without cell death through P2Y2 receptors. ATP led to overproduction of reactive oxygen species (ROS) through increased amount of NADPH oxidase (Nox) 2 proteins, due to increased physical interaction between Nox2 and canonical transient receptor potential 3 (TRPC3). This ATP-mediated formation of TRPC3-Nox2 complex was also pathophysiologically involved in nutritional deficiency-induced NRCM atrophy. Strikingly, knockdown of either TRPC3 or Nox2 suppressed nutritional deficiency-induced ATP release, as well as ROS production and NRCM atrophy. Taken together, we propose that TRPC3-Nox2 axis, activated by extracellular ATP, is the key component that mediates nutritional deficiency-induced cardiomyocyte atrophy.",
author = "Sudi, {Suhaini Binti} and Tomohiro Tanaka and Sayaka Oda and Kazuhiro Nishiyama and Akiyuki Nishimura and Caroline Sunggip and Supachoke Mangmool and Takuro Numaga-Tomita and Motohiro Nishida",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-019-46252-2",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - TRPC3-Nox2 axis mediates nutritional deficiency-induced cardiomyocyte atrophy

AU - Sudi, Suhaini Binti

AU - Tanaka, Tomohiro

AU - Oda, Sayaka

AU - Nishiyama, Kazuhiro

AU - Nishimura, Akiyuki

AU - Sunggip, Caroline

AU - Mangmool, Supachoke

AU - Numaga-Tomita, Takuro

AU - Nishida, Motohiro

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Myocardial atrophy, characterized by the decreases in size and contractility of cardiomyocytes, is caused by severe malnutrition and/or mechanical unloading. Extracellular adenosine 5′-triphosphate (ATP), known as a danger signal, is recognized to negatively regulate cell volume. However, it is obscure whether extracellular ATP contributes to cardiomyocyte atrophy. Here, we report that ATP induces atrophy of neonatal rat cardiomyocytes (NRCMs) without cell death through P2Y2 receptors. ATP led to overproduction of reactive oxygen species (ROS) through increased amount of NADPH oxidase (Nox) 2 proteins, due to increased physical interaction between Nox2 and canonical transient receptor potential 3 (TRPC3). This ATP-mediated formation of TRPC3-Nox2 complex was also pathophysiologically involved in nutritional deficiency-induced NRCM atrophy. Strikingly, knockdown of either TRPC3 or Nox2 suppressed nutritional deficiency-induced ATP release, as well as ROS production and NRCM atrophy. Taken together, we propose that TRPC3-Nox2 axis, activated by extracellular ATP, is the key component that mediates nutritional deficiency-induced cardiomyocyte atrophy.

AB - Myocardial atrophy, characterized by the decreases in size and contractility of cardiomyocytes, is caused by severe malnutrition and/or mechanical unloading. Extracellular adenosine 5′-triphosphate (ATP), known as a danger signal, is recognized to negatively regulate cell volume. However, it is obscure whether extracellular ATP contributes to cardiomyocyte atrophy. Here, we report that ATP induces atrophy of neonatal rat cardiomyocytes (NRCMs) without cell death through P2Y2 receptors. ATP led to overproduction of reactive oxygen species (ROS) through increased amount of NADPH oxidase (Nox) 2 proteins, due to increased physical interaction between Nox2 and canonical transient receptor potential 3 (TRPC3). This ATP-mediated formation of TRPC3-Nox2 complex was also pathophysiologically involved in nutritional deficiency-induced NRCM atrophy. Strikingly, knockdown of either TRPC3 or Nox2 suppressed nutritional deficiency-induced ATP release, as well as ROS production and NRCM atrophy. Taken together, we propose that TRPC3-Nox2 axis, activated by extracellular ATP, is the key component that mediates nutritional deficiency-induced cardiomyocyte atrophy.

UR - http://www.scopus.com/inward/record.url?scp=85068451940&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068451940&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-46252-2

DO - 10.1038/s41598-019-46252-2

M3 - Article

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 9785

ER -