SCM-198 protects endometrial stromal cells from oxidative damage through Bax/Bcl-2 and ERK signaling pathways
SCM-198 protects endometrial stromal cells from oxidative damage through Bax/Bcl-2 and ERK signaling pathways
复制标题
SCM-198 通过 Bax/Bcl-2 和 ERK 信号通路保护子宫内膜基质细胞免受氧化损伤
DOI：
10.1093/abbs/gmz035
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发表时间：
2019-06-01
影响因子：
3.7
通讯作者：
Du, Meirong
中科院分区：
文献类型：
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作者：
Li, Yunyun;Lin, Yikong;Du, Meirong
越来越多的证据表明，人子宫内膜间质细胞(ESCs)中积累的ROS和细胞凋亡与氧化应激所致的子宫内膜功能障碍密切相关，在多种妇科疾病和生殖相关疾病的病理过程中起着重要作用。SCM-198是益母草中的一种生物碱活性成分，已有报道具有抗氧化活性。然而，SCM-198预防子宫内膜损伤的具体机制尚不清楚。在本研究中，我们评估了SCM-198对过氧化氢(H_2O_2)诱导的ESCs氧化损伤的影响。用SCM-198处理ESCs 4h，然后用H_2O_2攻击。检测细胞形态变化、细胞凋亡率和细胞内ROS生成，以评估氧化损伤程度。流式细胞仪和免疫印迹分析检测Bax、Bcl2、活性半胱氨酸天冬氨酸蛋白酶3和丝裂原活化蛋白激酶通路的表达水平。通过实时聚合酶链式反应检测经典炎症细胞因子。结果表明，SCM-198可抑制H_2O_2诱导的ESCs的凋亡和ROS生成。H_2O_2诱导明显的细胞凋亡特征，包括DNA断裂、Bax/Bcl2上调、caspase-3激活和炎症细胞因子的分泌，这些都被SCM-198改善。此外，SCM-198可抑制过氧化氢诱导的细胞凋亡相关ERK1/2通路的激活。提示SCM-198可通过抑制氧化应激和减少细胞凋亡来保护ESCs免受氧化损伤。
Increasing amounts of evidence demonstrated that accumulative reactive oxygen species (ROS) and apoptosis of human endometrial stromal cells (ESCs) are closely associated with endometrial dysfunction induced by oxidative stress, which plays an important role in the pathological process of multiple gynecological and reproduction-related diseases. SCM-198, an alkaloid active component of Leonurus japonicas Houtt, has been reported to have anti-oxidative activity. However, the specific mechanisms of SCM-198 in the prevention of endometrial damage remain unknown. In the present study, we assessed the effect of SCM-198 on hydrogen peroxide (H2O2)-induced oxidative injury in ESCs. ESCs were pretreated with SCM-198 for 4 h and then challenged with H2O2. Morphology changes, apoptosis rate, and intracellular ROS production were measured to assess the level of oxidative injury. Flow cytometry and western blot analysis were performed to detect the expression levels of Bax, Bcl-2, active-caspase-3, and mitogen-activated protein kinases pathways. Classic inflammation cytokines were measured by real-time polymerase chain reactions. Our results showed that SCM-198 attenuated apoptosis and ROS generation of ESCs induced by H2O2. H2O2 induced the apparent apoptotic characteristics, including fragmentation of DNA, upregulation of Bax/Bcl2, activation of caspase-3, and secretion of inflammation cytokines, which were all ameliorated by SCM-198. Furthermore, H2O2-induced apoptosis-related ERK1/ 2 pathway activation was restrained by SCM-198 pretreatment. These findings suggested that SCM-198 could protect ESCs from oxidative injury, mainly by inhibiting oxidative stress and reducing apoptosis.