Melatonin attenuates angiotensin II-induced cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway
Melatonin attenuates angiotensin II-induced cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway
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DOI：
10.1007/s11010-016-2808-9
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发表时间：
2016-09
影响因子：
4.3
通讯作者：
Hongyan Su;Jingyuan Li;Tongshuai Chen;Na Li;Jie Xiao;Shu-jian Wang;Xiaobin Guo;Yi Yang;Peili Bu
中科院分区：
文献类型：
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作者：
Hongyan Su;Jingyuan Li;Tongshuai Chen;Na Li;Jie Xiao;Shu-jian Wang;Xiaobin Guo;Yi Yang;Peili Bu
褪黑素以其心脏保护作用而闻名；然而，褪黑素是否对心肌细胞肥大有治疗作用，以及这些作用的机制（如果存在的话）仍有待研究。亲环蛋白A （Cyclophilin A, CyPA）及其相应受体CD147存在于多种细胞中，在调节活性氧（reactive oxygen species， ROS）的产生中起着至关重要的作用。在本研究中，我们探讨了CyPA/CD147信号通路在血管紧张素II （Ang II）诱导的心肌细胞肥大中的作用，以及褪黑激素对培养的H9C2细胞Ang II诱导的损伤的保护作用。环孢素A是一种特异性的CyPA/CD147信号通路抑制剂，用于调控CyPA/CD147活性。然后，H9C2细胞在褪黑激素缺失或存在的情况下接受Ang II或CyPA治疗。我们的研究结果表明，在培养的H9C2细胞中，Ang II通过CyPA/CD147信号通路诱导心肌细胞肥大，并促进ROS的产生，而褪黑激素预处理可以以浓度依赖的方式阻断ROS的产生，并且CyPA/CD147信号通路抑制可以保护Ang II诱导的心肌细胞肥大。褪黑素对Ang ii诱导的心肌细胞肥大的保护作用至少部分依赖于CyPA/CD147的抑制。
Melatonin is well known for its cardioprotective effects; however, whether melatonin exerts therapeutic effects on cardiomyocyte hypertrophy remains to be investigated, as do the mechanisms underlying these effects, if they exist. Cyclophilin A (CyPA) and its corresponding receptor, CD147, which exists in a variety of cells, play crucial roles in modulating reactive oxygen species (ROS) production. In this study, we explored the role of the CyPA/CD147 signaling pathway in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy and the protective effects exerted by melatonin against Ang II-induced injury in cultured H9C2 cells. Cyclosporine A, a specific CyPA/CD147 signaling pathway inhibitor, was used to manipulate CyPA/CD147 activity. H9C2 cells were then subjected to Ang II or CyPA treatment in either the absence or presence of melatonin. Our results indicate that Ang II induces cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway and promotes ROS production, which can be blocked by melatonin pretreatment in a concentration-dependent manner, in cultured H9C2 cells and that CyPA/CD147 signaling pathway inhibition protects against Ang II-induced cardiomyocyte hypertrophy. The protective effects of melatonin against Ang II-induced cardiomyocyte hypertrophy depend at least partially on CyPA/CD147 inhibition.