Capsaicin Alleviates the Deteriorative Mitochondrial Function by Upregulating 14-3-3η in Anoxic or Anoxic/Reoxygenated Cardiomyocytes
Capsaicin Alleviates the Deteriorative Mitochondrial Function by Upregulating 14-3-3η in Anoxic or Anoxic/Reoxygenated Cardiomyocytes
复制标题
辣椒素通过上调缺氧或缺氧/复氧心肌细胞中的 14-3-3δ 来减轻线粒体功能恶化
DOI：
10.1155/2020/1750289
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发表时间：
2020-03-04
影响因子：
--
通讯作者：
He, Ming
中科院分区：
文献类型：
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作者：
Qiao, Yang;Hu, Tianhong;He, Ming
活性氧物种(ROS)是缺陷电子传递链(ETC)的副产物。氧化还原对，GSH/GSSG和NAD+/NADH，通过促进细胞内/线粒体(MT)氧化还原动态平衡，作为抵抗过量ROS产生的内部防御，在生理上发挥着重要作用。单纯缺氧和缺氧/复氧(A/R)是不同的病理过程。在这项研究中，我们使用原代培养的新生大鼠心肌细胞体外模型来测量辣椒素(Cap)对这些病理过程的影响。结果表明，ROS的过量产生与GSH/GSSG紊乱密切相关，NAD+/NADH抑制了线粒体复合体I和III的活性，降低了耗氧率，提高了胞外酸化速率。在缺氧或A/R期间，这些指标相互作用，导致线粒体功能恶化。CAP通过挽救NAD+/NADH、GSH/GSSG、线粒体复合体I/III活性和细胞能量代谢，保护心肌细胞免受A/R损伤的不同阶段。重要的是，CaP介导的心肌细胞保护性磷酸丝氨酸结合蛋白14-3-3η的上调，改善了由破坏性氧化还原状态和受损等引起的mt功能。结论：单纯缺氧组和A/R组的氧化还原对、线粒体复合体I/III和代谢平衡均有显著差异，CaP通过上调14-3-3-η对心肌细胞的上述损伤起到保护作用。
Reactive oxygen species (ROS) are byproducts of a defective electron transport chain (ETC). The redox couples, GSH/GSSG and NAD+/NADH, play an essential role in physiology as internal defenses against excessive ROS generation by facilitating intracellular/mitochondrial (mt) redox homeostasis. Anoxia alone and anoxia/reoxygenation (A/R) are dissimilar pathological processes. In this study, we measured the impact of capsaicin (Cap) on these pathological processes using a primary cultured neonatal rat cardiomyocyte in vitro model. The results showed that overproduction of ROS was tightly associated with disturbed GSH/GSSG and NAD+/NADH suppressed mt complex I and III activities, decreased oxygen consumption rates, and elevated extracellular acidification rates. During anoxia or A/R period, these indices interact with each other causing the mitochondrial function to worsen. Cap protected cardiomyocytes against the different stages of A/R injury by rescuing NAD+/NADH, GSH/GSSG, and mt complex I/III activities and cellular energy metabolism. Importantly, Cap-mediated upregulation of 14-3-3η, a protective phosphoserine-binding protein in cardiomyocytes, ameliorated mt function caused by a disruptive redox status and an impaired ETC. In conclusion, redox pair, mt complex I/III, and metabolic equilibrium were significantly different in anoxia alone and A/R injury; Cap through upregulating 14-3-3η plays a protection against the above injury in cardiomyocyte.