Overexpression of COX5A protects H9c2 cells against doxorubicin-induced cardiotoxicity
Overexpression of COX5A protects H9c2 cells against doxorubicin-induced cardiotoxicity
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COX5A 过度表达可保护 H9c2 细胞免受阿霉素诱导的心脏毒性
DOI：
10.1016/j.bbrc.2020.01.013
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发表时间：
2020
影响因子：
3.1
通讯作者：
Junbo Ge
中科院分区：
文献类型：
--
作者：
Peipei Zhang;Zhangwei Chen;Danbo Lu;Yuan Wu;Mengkang Fan;Juying Qian;Junbo Ge
线粒体功能障碍在阿霉素 (DOX) 诱导的心肌病中起着关键作用。细胞色素氧化酶亚基 5A (COX5A) 是参与线粒体电子传递的末端氧化酶的核编码亚基。尽管COX5A似乎在调节COX的生理活性并参与能量代谢中发挥关键作用，但COX5A在DOX诱导的心脏毒性中的作用仍不清楚。在这项研究中，我们发现 DOX 处理 H9c2 细胞后 COX5A 显着下调。 H9c2 细胞中 COX5A 的过表达可有效减弱 DOX 诱导的细胞凋亡。同时，DOX 诱导的线粒体膜电位降低可以通过 COX5A 过表达来保留。此外，COX5A 过表达缓解了 DOX 诱导的线粒体呼吸抑制，因为基础呼吸、最大呼吸、ATP 产生和备用呼吸能力增加。这些发现表明，COX5A 的上调可能会抑制 DOX 处理的 H9c2 细胞的凋亡并减轻线粒体功能障碍。因此，COX5A 可能有潜力在临床上用作 DOX 诱导的心脏毒性的治疗靶点。
Mitochondrial dysfunction plays a pivotal role in doxorubicin (DOX)-induced cardiomyopathy. Cytochromecoxidase subunit 5A (COX5A) is a nuclear-encoded subunit of the terminal oxidase involved in mitochondrial electron transport. Although COX5A appears to play a key role in modulating the physiological activity of COX and involve in energy metabolism, the involvement of COX5A in DOX-induced cardiotoxicity remains unclear. In this study, we showed that COX5A was significantly downregulated by DOX treatment of H9c2 cells. Overexpression of COX5A in H9c2 cells effectively attenuated DOX-induced apoptosis. Meanwhile, DOX-induced decrease in mitochondrial membrane potential could be reserved by COX5A overexpression. Furthermore, COX5A overexpression relieved the DOX-induced suppression of mitochondrial respiration, due an increase in basal respiration, maximal respiration, ATP production, and spare respiratory capacity. These findings indicate that up-regulation of COX5A may inhibit the apoptosis and alleviate the mitochondrial dysfunction of DOX-treated H9c2 cells. Thus, COX5A may have potential for clinical use as a therapeutic target in DOX-induced cardiotoxicity.