Ma 2019 Biochem Biophys Res Commun
|Ma T, Lin S, Wang B, Wang Q, Xia W, Zhang H, Cui Y, He C, Wu H, Sun F, Zhao Z, Gao P, Zhu Z, Liu D (2019) TRPC3 deficiency attenuates high salt-induced cardiac hypertrophy by alleviating cardiac mitochondrial dysfunction. Biochem Biophys Res Commun 519:674-81.|
Ma Tianyi, Lin Shaoyang, Wang Bin, Wang Qianran, Xia Weijie, Zhang Hexuan, Cui Yuanting, He Chengkang, Wu Hao, Sun Famg, Zhao Zhigang, Gao Peng, Zhu Zhiming, Liu Daoyan (2019) Biochem Biophys Res Commun
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.
Copyright © 2019 Elsevier Inc. All rights reserved. • Keywords: Calcium homeostasis, Cardiac hypertrophy, High salt diet, Mitochondria, TRPC3 • Bioblast editor: Plangger M • O2k-Network Lab: CN Chongqing Zhu Z
Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style
Organism: Mouse Tissue;cell: Heart Preparation: Permeabilized cells Enzyme: Complex I, Complex II;succinate dehydrogenase
Coupling state: LEAK, OXPHOS, ET Pathway: N, S, NS, ROX HRR: Oxygraph-2k