Taurine attenuates isoproterenol-induced H9c2 cardiomyocytes hypertrophy by improving antioxidative ability and inhibiting calpain-1-mediated apoptosis

Taurine attenuates isoproterenol-induced H9c2 cardiomyocytes hypertrophy by improving antioxidative ability and inhibiting calpain-1-mediated apoptosis
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DOI:
10.1007/s11010-020-03733-7
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发表时间:
2020-06-01
影响因子:
4.3
通讯作者:
Hu, Jianmin
Hu, Jianmin
中科院分区:
生物学3区
文献类型:
--
作者:
Li, Weiwei;Yang, Jiancheng;Hu, Jianmin

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病理性心肌肥大最终伴随着心肌细胞凋亡。细胞凋亡主要与钙蛋白酶1介导的凋亡途径有关。研究表明,牛磺酸可通过抗氧化、抗凋亡等作用维持心脏健康,但牛磺酸对心肌肥厚的影响尚不清楚。本研究旨在确定牛磺酸是否能抑制异丙肾上腺素(ISO)诱导的肥大心肌细胞中钙蛋白酶-1介导的凋亡途径。我们发现牛磺酸可以抑制细胞表面积的增加,并降低肥大标志物心钠素、脑钠素和β-肌球蛋白重链的蛋白表达水平。牛磺酸还降低ROS、细胞内Ca 2+超载和线粒体膜电位。牛磺酸通过降低calpain-1、Bax、t-Bid、细胞色素c、Apaf-1、cleaved caspase-9和cleaved caspase-3的蛋白表达,增强calpastatin和Bcl-2的蛋白表达,抑制心肌细胞凋亡。Calpain-1小干扰RNA转染结果显示与牛磺酸预防组相似的抗凋亡作用。但与两种处理相比,牛磺酸对caspase-9表达的抑制作用更明显。因此,我们认为牛磺酸通过抑制氧化应激、细胞内钙超载、钙蛋白酶-1介导的凋亡途径和切割的caspase-9水平来防止ISO诱导的H9 c2心肌细胞肥大。图形摘要
Pathological cardiac hypertrophy is ultimately accompanied by cardiomyocyte apoptosis. Apoptosis mainly related to calpain-1-mediated apoptotic pathways. Studies had proved that taurine can maintain heart health through antioxidation and antiapoptotic functions, but the effect of taurine on cardiac hypertrophy is still unclear. This study aimed to determine whether taurine could inhibit calpain-1-mediated mitochondria-dependent apoptotic pathways in isoproterenol (ISO)-induced hypertrophic cardiomyocytes. We found that taurine could inhibit the increase in cell surface area and reduce the protein expression levels of the hypertrophic markers atrial natriuretic peptide, brain natriuretic polypeptide, and beta-myosin heavy chain. Taurine also reduced ROS, intracellular Ca2+ overload and mitochondrial membrane potential. Moreover, taurine inhibited cardiomyocyte apoptosis by decreasing the protein expression of calpain-1, Bax, t-Bid, cytosolic cytochrome c, Apaf-1, cleaved caspase-9 and cleaved caspase-3 and by enhancing calpastatin and Bcl-2 protein expression. Calpain-1 small interfering RNA transfection results showed similar antiapoptotic effects as the taurine prevention group. However, compared with the two treatments, taurine inhibited the expression of cleaved caspase-9 more significantly. Therefore, we believe that taurine prevents ISO-induced H9c2 cardiomyocyte hypertrophy by inhibiting oxidative stress, intracellular Ca2+ overload, the calpain-1-mediated mitochondria-dependent apoptotic pathway and cleaved caspase-9 levels. Graphic abstract