TRPC3 deficiency attenuates high salt-induced cardiac hypertrophy by alleviating cardiac mitochondrial dysfunction
TRPC3 deficiency attenuates high salt-induced cardiac hypertrophy by alleviating cardiac mitochondrial dysfunction
复制标题
TRPC3 缺乏通过减轻心脏线粒体功能障碍来减轻高盐诱导的心脏肥大
DOI：
10.1016/j.bbrc.2019.09.018
复制
发表时间：
2019-11-19
影响因子：
3.1
通讯作者：
Liu, Daoyan
中科院分区：
文献类型：
--
作者：
Ma, Tianyi;Lin, Shaoyang;Liu, Daoyan
长期高盐摄入导致心肌肥大，但其机制尚不清楚。瞬时受体电位通道（transient receptor potential channel，canonical 3，TRPC 3）位于线粒体内，调节线粒体钙离子和活性氧的产生。在此，我们研究了TRPC 3是否通过损害心脏线粒体功能参与高盐诱导的心脏肥大。高盐处理增加了心肌细胞线粒体TRPC 3的表达，并伴随着线粒体钙摄取和ROS产生的增加。TRPC 3的抑制显著降低高盐诱导的ROS产生，通过刺激氧化磷酸化促进ATP产生，并增加心肌细胞线粒体中的酶活性。此外，TRPC 3缺乏抑制体内高盐诱导的心脏肥大。长期高盐饮食增加心脏线粒体TRPC 3表达，心脏肥大标志物心房利钠肽（ANP）、脑利钠肽（BNP）和β-肌球蛋白重链（β-MHC）表达升高，ATP产生和线粒体复合物I和II酶活性以TRPC 3依赖性方式降低。TRPC 3缺乏通过改善TRPC 3介导的心脏线粒体功能障碍来拮抗高盐饮食介导的心脏肥大。因此，TRPC 3可能是预防高盐诱导的心脏损伤的新靶点。(C)2019爱思唯尔公司All rights reserved.
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 beta-myosin heavy chain (beta-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. (C) 2019 Elsevier Inc. All rights reserved.