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Dihydroartemisinin induces ER stress-dependent apoptosis of Echinococcus protoscoleces in vitro
Acta Biochimica et Biophysica Sinica ( IF 3.7 ) Pub Date : 2020-10-21 , DOI: 10.1093/abbs/gmaa101
Rongji Ma 1 , Wenjuan Qin 2 , Yuanmao Xie 3 , Ziwei Han 1 , Shuojie Li 4 , Yufeng Jiang 1, 5 , Hailong Lv 6
Affiliation  

In this study, we investigated the effect of dihydroartemisinin on Echinococcus protoscoleces and explored the role of endoplasmic reticulum stress in this process. Echinococcus protoscoleces were collected and cultured in RPMI 1640 medium. Changes in the expressions of glucose-regulated protein 78 (GRP-78), caspase-12, and C/EBP homologous protein (CHOP) were assessed through confocal immunofluorescence and western blot analysis. Cell viability and morphological changes were observed under a light microscope. The ultrastructure of protoscoleces was observed by scanning electron microscopy and transmission electron microscopy. Caspase-3 activity was detected using an enzyme assay kit. After dihydroartemisinin treatment, the protoscoleces showed loss of viability, and morphological changes including soma contraction, blebs formation, hooks loss, microtrichia destruction, and development of lipid droplets was observed. The levels of caspase-12 and CHOP were increased within 2 days of dihydroartemisinin treatment. However, the levels of GRP-78, caspase-12, and CHOP were decreased in 4 days. Furthermore, caspase-3 activity was increased after treatment with different concentrations of dihydroartemisinin. Dihydroartemisinin can induce apoptosis in protoscoleces via the ER stress-caspase-3 apoptotic pathway in vitro. These results indicate that dihydroartemisinin is a potentially valuable therapeutic agent against echinococcosis.

中文翻译:

双氢青蒿素体外诱导棘球绦虫的内质网应激依赖性凋亡

在这项研究中,我们研究了双氢青蒿素对棘球绦虫的影响,并探讨了内质网应激在该过程中的作用。棘球绦虫收集原头节并在 RPMI 1640 培养基中培养。通过共聚焦免疫荧光和蛋白质印迹分析评估葡萄糖调节蛋白 78 (GRP-78)、caspase-12 和 C/EBP 同源蛋白 (CHOP) 表达的变化。在光学显微镜下观察细胞活力和形态变化。通过扫描电子显微镜和透射电子显微镜观察原头节的超微结构。使用酶测定试剂盒检测 Caspase-3 活性。在双氢青蒿素处理后,原头颈表现出活力丧失,并观察到形态学变化,包括体细胞收缩、水泡形成、钩状脱落、小毛状体破坏和脂滴形成。caspase-12 和 CHOP 的水平在双氢青蒿素治疗的 2 天内增加。然而,GRP-78、caspase-12 和 CHOP 的水平在 4 天内下降。此外,用不同浓度的双氢青蒿素处理后,caspase-3 活性增加。双氢青蒿素可通过内质网应激-caspase-3 凋亡通路诱导原头颈细胞凋亡体外。这些结果表明双氢青蒿素是一种潜在的有价值的治疗棘球蚴病的药物。
更新日期:2020-11-23
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