Trichomonas vaginalis induces apoptosis via ROS and ER stress response through ER-mitochondria crosstalk in SiHa cells.
Trichomonas vaginalis induces apoptosis via ROS and ER stress response through ER-mitochondria crosstalk in SiHa cells.
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DOI：
10.1186/s13071-021-05098-2
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发表时间：
2021-12-11
影响因子：
3.2
通讯作者：
Lee YH
中科院分区：
文献类型：
--
作者：
Gao FF;Quan JH;Lee MA;Ye W;Yuk JM;Cha GH;Choi IW;Lee YH
阴道毛滴虫引起女性宫颈阴道黏膜病变；然而，其发病机制尚不清楚。我们研究了内质网（ER）在阴道梭菌诱导人宫颈癌SiHa细胞凋亡中的作用及其分子机制。采用免疫细胞化学、流式细胞术、5,5 ',6,6 ' -四氯-1,1 ',3,3 ' -四乙基-碘化胺染料染色和western blotting检测细胞凋亡、活性氧（ROS）产生、线粒体膜电位（MMP）、内质网应激反应和Bcl-2家族蛋白表达。阴道毛滴虫诱导SiHa细胞线粒体ROS产生、凋亡、内质网应激反应和线粒体功能障碍，如MMP去极化和Bcl-2家族蛋白失衡，以寄生虫负担和感染时间依赖的方式发生。n -乙酰半胱氨酸（ROS清除剂）或4-苯基丁酸（4-PBA；内质网应激抑制剂）预处理可显著缓解细胞凋亡、线粒体ROS生成、线粒体功能障碍和内质网应激反应，且呈剂量依赖性。此外，阴道曲霉诱导SiHa细胞凋亡信号调节激酶1 （ASK1）和c-Jun n -末端激酶（JNK）的磷酸化，而4-PBA或SP600125 （JNK抑制剂）预处理显著减弱SiHa细胞中ASK1/JNK的磷酸化、线粒体功能障碍、凋亡和内质网应激反应，且呈剂量依赖性。此外，阴道滴虫的排泄/分泌产物还能诱导SiHa细胞的线粒体ROS生成、凋亡和内质网应激反应，且具有时间依赖性。阴道毛滴虫通过线粒体ROS和内质网应激反应诱导细胞凋亡，并通过IRE1/ASK1/JNK/Bcl-2家族蛋白通路促进内质网应激介导的SiHa细胞线粒体凋亡。这些数据表明，阴道炎诱导的细胞凋亡通过ER -线粒体串扰受到ROS和内质网应激反应的影响。在线版本包含补充材料，可在10.1186/s13071-021-05098-2获得。
Trichomonas vaginalis causes lesions on the cervicovaginal mucosa in women; however, its pathogenesis remains unclear. We have investigated the involvement of the endoplasmic reticulum (ER) in the induction of apoptosis by T. vaginalis and its molecular mechanisms in human cervical cancer SiHa cells. Apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), ER stress response and Bcl-2 family protein expression were evaluated using immunocytochemistry, flow cytometry, 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide dye staining and western blotting. Trichomonas vaginalis induced mitochondrial ROS production, apoptosis, the ER stress response and mitochondrial dysfunction, such as MMP depolarization and an imbalance in Bcl-2 family proteins, in SiHa cells in a parasite burden- and infection time-dependent manner. Pretreatment with N-acetyl cysteine (ROS scavenger) or 4-phenylbutyric acid (4-PBA; ER stress inhibitor) significantly alleviated apoptosis, mitochondrial ROS production, mitochondrial dysfunction and ER stress response in a dose-dependent manner. In addition, T. vaginalis induced the phosphorylation of apoptosis signal regulating kinase 1 (ASK1) and c-Jun N-terminal kinases (JNK) in SiHa cells, whereas 4-PBA or SP600125 (JNK inhibitor) pretreatment significantly attenuated ASK1/JNK phosphorylation, mitochondrial dysfunction, apoptosis and ER stress response in SiHa cells, in a dose-dependent manner. Furthermore, T. vaginalis excretory/secretory products also induced mitochondrial ROS production, apoptosis and the ER stress response in SiHa cells, in a time-dependent manner. Trichomonas vaginalis induces apoptosis through mitochondrial ROS and ER stress responses, and also promotes ER stress-mediated mitochondrial apoptosis via the IRE1/ASK1/JNK/Bcl-2 family protein pathways in SiHa cells. These data suggest that T. vaginalis-induced apoptosis is affected by ROS and ER stress response via ER–mitochondria crosstalk. The online version contains supplementary material available at 10.1186/s13071-021-05098-2.
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硅蛋白诱导线粒体NOX4介导的内质网应激反应及其随后的凋亡。
影响因子：
3.8
作者：
Kim SH;Kim KY;Yu SN;Seo YK;Chun SS;Yu HS;Ahn SC
通讯作者：
Ahn SC
影响因子：
16
作者：
Bhola PD;Letai A
通讯作者：
Letai A
DOI：
10.1007/s00018-015-2052-6
发表时间：
2016-01
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Schwarz DS;Blower MD
通讯作者：
Blower MD
DOI：
10.1051/parasite/2014054
发表时间：
2014
期刊：
Parasite (Paris, France)
影响因子：
--
作者：
Hernández HM;Marcet R;Sarracent J
通讯作者：
Sarracent J
影响因子：
8.8
作者：
Bayir, H
通讯作者：
Bayir, H