异甜菊醇通过激活 ERK1/2 保护 H9c2 细胞免受缺氧再复氧损伤。
Isosteviol Protects H9c2 Cells Against Hypoxia-reoxygenation by Activating ERK1/2.
机构信息
Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.
Department of Basic and Clinical Sciences, University of Nicosia Medical School, Nicosia CY-1700, Cyprus.
出版信息
Cardiovasc Hematol Disord Drug Targets. 2021;21(1):73-77. doi: 10.2174/1871529X21666210216122022.
AIMS
In the present study, we have investigated the cardioprotective properties of Isosteviol (STV) under conditions of hypoxia-reoxygenation and elucidated the underlying mechanism.
BACKGROUND
In our previous studies, we have determined that STV exhibits neuro- and cardio-protective properties. However, the mechanism underlying STV-induced cardioprotection has not yet been fully understood.
METHODS
All experiments were performed on rat heart embryonic H9c2 cell line. To induce hypoxia- reoxygenation, cells were exposed to 1% oxygen (in no glucose and no sodium pyruvate DMEM) following by reoxygenation (using fully supplemented MEM). Cells viability was tested by MTT assay, and protein levels were compared by Western blotting.
RESULTS
Treatment of heart embryonic H9c2 cells with STV (10 μM) significantly increased the survival of cells exposed to hypoxia-reoxygenation. STV (10 μM) activated ERK1/2 and DRP1 in hypoxia-reoxygenation, but did not have any effects on ERK1/2 or DRP1 in normoxia. STV (10 μM) did not regulate CAMKII, AKT or AMPK signaling pathways.
CONCLUSION
Taken all together, our findings demonstrate that 1) STV protects H9c2 cells against hypoxia-reoxygenation and that 2) this effect is mediated via ERK1/2. The property of STV that selectively activates ERK1/2 in cells exposed to stress, but not in cells under non-stress conditions, makes this compound a promising candidate-drug for therapy against myocardial ischemia-reperfusion in clinical practice.
目的
在本研究中，我们研究了异甜醇（STV）在缺氧再复氧条件下的心脏保护特性，并阐明了其潜在机制。
背景
在我们之前的研究中，我们已经确定 STV 具有神经和心脏保护特性。然而，STV 诱导心脏保护的机制尚未完全阐明。
方法
所有实验均在大鼠心脏胚胎 H9c2 细胞系上进行。为了诱导缺氧-复氧，细胞先在 1%氧气（无葡萄糖和无丙酮酸钠的 DMEM）中孵育，然后再复氧（使用完全补充的 MEM）。通过 MTT 测定法测试细胞活力，并通过 Western 印迹法比较蛋白水平。
结果
用 STV（10 μM）处理心脏胚胎 H9c2 细胞可显著提高暴露于缺氧-复氧的细胞存活率。STV（10 μM）在缺氧-复氧中激活了 ERK1/2 和 DRP1，但在常氧中对 ERK1/2 或 DRP1 没有任何影响。STV（10 μM）不调节 CAMKII、AKT 或 AMPK 信号通路。
结论
综上所述，我们的研究结果表明 1）STV 可保护 H9c2 细胞免受缺氧-复氧损伤，2）这种作用是通过 ERK1/2 介导的。STV 的特性是选择性地在应激条件下激活细胞中的 ERK1/2，而在非应激条件下不激活，这使得该化合物成为治疗临床实践中心肌缺血再灌注的有前途的候选药物。
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