TRPC3 deficiency attenuates high salt-induced cardiac hypertrophy by alleviating cardiac mitochondrial dysfunction.

Abstract

Long-term high salt intake leads to cardiac hypertrophy, but the mechanism remains elusive. Transient receptor potential channel, canonical 3(TRPC3), located in mitochondria, regulates mitochondrial calcium and reactive oxygen species(ROS) production. Herein, we investigated whether TRPC3 participates in high salt-induced cardiac hypertrophy by impairing cardiac mitochondrial function. High salt treatment increased the expression of mitochondrial TRPC3 in cardiomyocytes, accompanied by enhanced mitochondrial calcium uptake and elevated ROS production. Inhibition of TRPC3 significantly reduced high salt-induced ROS generation, promoted ATP production by stimulating oxidative phosphorylation, and increased enzyme activity in mitochondria in cardiomyocytes. Additionally, TRPC3 deficiency inhibited high salt-induced cardiac hypertrophy in vivo. A long-term high salt diet increased cardiac mitochondrial TRPC3 expression, elevated expression of cardiac hypertrophic markers atrial natriuretic peptide (ANP),brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) and decreased ATP production and mitochondrial complex I and II enzyme activity in a TRPC3-dependent manner. TRPC3 deficiency antagonises high salt diet-mediated cardiac hypertrophy by ameliorating TRPC3-mediated cardiac mitochondrial dysfunction. TRPC3 may therefore represent a novel target for preventing high salt-induced cardiac damage.

• Authors: Tianyi Ma, Shaoyang Lin, Bin Wang, Qianran Wang, Weijie Xia, Hexuan Zhang, Yuanting Cui, Chengkang He, Hao Wu, Fang Sun, Zhigang Zhao, Peng Gao, Zhiming Zhu, Daoyan Liu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 519 Issue 4 Pg. 674-681 (11 19 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 31543348 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Reactive Oxygen Species
• Sodium Chloride, Dietary
• TRPC Cation Channels
• TRPC3 cation channel
• Natriuretic Peptide, Brain
• Atrial Natriuretic Factor
• Adenosine Triphosphate
• Electron Transport Complex II
• Electron Transport Complex I
• Calcium

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Atrial Natriuretic Factor (metabolism)
• Calcium (metabolism)
• Cardiomegaly (etiology, genetics, metabolism)
• Cell Line
• Electron Transport Complex I (metabolism)
• Electron Transport Complex II (metabolism)
• Mice, Knockout
• Mitochondria (metabolism)
• Myocytes, Cardiac (drug effects, metabolism)
• Natriuretic Peptide, Brain (metabolism)
• Rats
• Reactive Oxygen Species (metabolism)
• Sodium Chloride, Dietary (adverse effects)
• TRPC Cation Channels (deficiency, genetics)