Department of Histology and Embryology, School of Medicine, Shihezi University, Shihezi 832000, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi 832000, China.
Acta Biochim Biophys Sin (Shanghai). 2018 Jun 1;50(6):579-585. doi: 10.1093/abbs/gmy041.
Cystic echinococcosis is a severe parasitic disease that commonly affects the liver and causes abscesses or rupture into the surrounding tissues, leading to multiple complications, such as shock, severe abdominal pain, and post-treatment abscess recurrence. Currently, there are no efficient measures to prevent these complications. We previously confirmed that arsenic trioxide (As2O3) exhibited in vitro cytotoxicity against Echinococcus granulosus protoscoleces. In the present study, we aimed to explore the mechanism of As2O3-induced E. granulosus protoscoleces apoptosis. After exposing E. granulosus protoscoleces to 0, 4, 6, and 8 μM As2O3, reactive oxygen species (ROS) level was detected by fluorescence microscopy; superoxide dismutase (SOD), and caspase-3 activities were measured; intracellular Ca2+ was detected by flow cytometry; GRP-78 and caspase-12 protein levels were measured by western blot analysis. Our results showed that the expression of caspase-3 was gradually increased and the expression of SOD was gradually decreased in As2O3-treated groups of protoscoleces. Simultaneously, fluorescence microscopy and flow cytometry showed that the ROS level and the intracellular Ca2+ level were increased in a time- and dose-dependent manner. Western blot analysis showed that the expressions of GRP-78 and caspase-12 were higher in As2O3-treated groups than in the control group. These results suggest that As2O3-induced apoptosis in E. granulosus protoscoleces is related to elevation of ROS level, disruption of intracellular Ca2+ homeostasis, and endoplasmic reticulum stress. These mechanisms can be targeted in the future by safer and more effective drugs to prevent recurrence of cystic echinococcosis.
棘球蚴病是一种严重的寄生虫病，常累及肝脏并导致脓肿或破裂至周围组织，引起多种并发症，如休克、剧烈腹痛和治疗后脓肿复发。目前，尚无有效的预防这些并发症的措施。我们之前证实三氧化二砷（As2O3）对细粒棘球蚴原头蚴具有体外细胞毒性。本研究旨在探讨 As2O3 诱导细粒棘球蚴原头蚴凋亡的机制。将细粒棘球蚴原头蚴暴露于 0、4、6 和 8 μM 的 As2O3 后，通过荧光显微镜检测活性氧（ROS）水平；测量超氧化物歧化酶（SOD）和 caspase-3 活性；通过流式细胞术检测细胞内 Ca2+；通过 Western blot 分析检测 GRP-78 和 caspase-12 蛋白水平。结果显示，在 As2O3 处理的原头蚴中，caspase-3 的表达逐渐增加，SOD 的表达逐渐降低。同时，荧光显微镜和流式细胞术显示，ROS 水平和细胞内 Ca2+水平呈时间和剂量依赖性增加。Western blot 分析显示，As2O3 处理组的 GRP-78 和 caspase-12 的表达高于对照组。这些结果表明，As2O3 诱导细粒棘球蚴原头蚴凋亡与 ROS 水平升高、细胞内 Ca2+稳态破坏和内质网应激有关。未来可以通过更安全、更有效的药物针对这些机制，预防包虫病的复发。
