Elatoside C protects against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes through the reduction of endoplasmic reticulum stress partially depending on STAT3 activation
Elatoside C protects against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes through the reduction of endoplasmic reticulum stress partially depending on STAT3 activation
复制标题
Elatoside C 通过减少内质网应激来防止 H9c2 心肌细胞缺氧/复氧诱导的细胞凋亡，部分取决于 STAT3 激活
DOI：
10.1007/s10495-014-1039-3
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发表时间：
2014-12-01
期刊：
影响因子：
7.2
通讯作者：
Sun, Xiao-bo
中科院分区：
文献类型：
--
作者：
Wang, Min;Meng, Xiang-bao;Sun, Xiao-bo
内质网（ER）应激诱导的细胞凋亡被认为会导致心肌缺血再灌注（I/R）损伤。 Elatoside C 是从龙牙楤木中分离出来的主要三萜类化合物之一，已知具有心脏保护作用。然而，其对心肌细胞I/R损伤的影响尚未明确。本研究旨在探讨Elatside C对缺氧/复氧（H/R）诱导的H9c2心肌细胞损伤的可能保护作用及其潜在机制。 H9c2 心肌细胞在存在 Elatoside C 的情况下进行 H/R。我们的结果表明，Elatoside C (25 μM) 处理可显着防止 H/R 诱导的细胞死亡，如细胞活力提高、线粒体膜电位维持、线粒体 ROS 减少和心肌细胞凋亡减少所证明的那样 (P < 0.05)。这些变化与 ER 应激相关细胞凋亡标记物（GRP78、CHOP、Caspase-12 和 JNK）的抑制以及 STAT3 磷酸化的增加和 Bcl2/Bax 比率的增加有关。此外，Elatoside C 的这些作用可以被 STAT3 抑制剂 Stattic 阻止。总而言之，这些结果表明，Elatoside C 很可能通过激活 STAT3 途径并减少 ER 应激相关的细胞凋亡来减轻 H/R 诱导的心肌细胞凋亡。
Endoplasmic reticulum (ER) stress-induced apoptosis has been suggested to contribute to myocardial ischemia-reperfusion (I/R) injury. Elatoside C is one of the major triterpenoid compounds isolated from Aralia elata that is known to be cardioprotective. However, its effects on I/R injury to cardiac myocytes have not been clarified. This study aimed to investigate the possible protective effect of Elatoside C against hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocyte injury and its underlying mechanisms. H9c2 cardiomyocytes were subjected to H/R in the presence of Elatoside C. Our results showed that Elatoside C (25 mu M) treatment provided significant protection against H/R-induced cell death, as evidenced by improved cell viability, maintained mitochondrial membrane potential, diminished mitochondrial ROS, and reduced apoptotic cardiomyocytes (P < 0.05). These changes were associated with the inhibition of ER stress-associated apoptosis markers (GRP78, CHOP, Caspase-12 and JNK), as well as the increased phosphorylation of STAT3 and an increased Bcl2/Bax ratio. Moreover, these effects of Elatoside C were prevented by the STAT3 inhibitor Stattic. Taken together, these results suggested that Elatoside C can alleviate H/R-induced cardiomyocyte apoptosis most likely by activating the STAT3 pathways and reducing ER stress-associated apoptosis.