Trichonomas vaginalis Metalloproteinase Induces Apoptosis of SiHa Cells through Disrupting the Mcl-1/Bim and Bcl-xL/Bim Complexes
Trichonomas vaginalis Metalloproteinase Induces Apoptosis of SiHa Cells through Disrupting the Mcl-1/Bim and Bcl-xL/Bim Complexes
复制标题
阴道毛滴虫金属蛋白酶通过破坏 Mcl-1/Bim 和 Bcl-xL/Bim 复合物诱导 SiHa 细胞凋亡
DOI：
10.1371/journal.pone.0110659
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发表时间：
2014-10-24
期刊：
影响因子：
3.7
通讯作者：
Lee, Young-Ha
中科院分区：
文献类型：
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作者：
Quan, Juan-Hua;Kang, Byung-Hun;Lee, Young-Ha
探讨金属蛋白酶和Bcl-2家族蛋白在毛迷走神经炎中的作用。阴道炎诱导的人宫颈癌细胞（SiHa细胞）和阴道上皮细胞（MS 74细胞）凋亡。vagelis，T.迷走神经排泄和分泌产物（ESP）和T. vagulocytosis裂解物，无论有或没有特异性金属蛋白酶抑制剂1，10-菲咯啉（1，10-PT），并检查凋亡事件和Bcl-2信号。活的T。迷走神经和T.迷走神经ESP诱导细胞色素c释放到胞质溶胶中，激活caspase-3和caspase-9，并切割PARP。此外，Live T。迷走神经，但不是T。vagulocytosis裂解物，诱导促凋亡Bim蛋白的切割。活的T。迷走神经和T.迷走神经ESP，但不是T。迷走神经细胞裂解物诱导抗凋亡Bcl-xL和Mcl-1蛋白的剂量依赖性切割，并降低Bcl-xL/Bim和Mcl-1/Bim复合物的缔合水平。我们进行了明胶酶谱和酪蛋白水解试验的活T。迷走神经和T.迷走神经电生理检查，以确定诱发癫痫的因素。两个活的T。迷走神经和ESP含有高水平的金属蛋白酶，其活性被1，10-PT处理显著抑制。此外，1，10-PT阻断了Bcl-xL、Mcl-1、PARP、caspase-3和caspase-9的切割，以及细胞色素c释放到胞质溶胶中，并显著增加了Bcl-xL/Bim和Mcl-1/Bim蛋白复合物的结合水平，使其恢复到正常水平。结果表明，T.迷走神经刺激通过Bcl-xL/Bim和Mcl-1/Bim复合物的解离诱导SiHa细胞的凋亡，并且该凋亡被金属蛋白酶抑制剂1，10-PT阻断。这些结果扩展了我们对金属蛋白酶在T.阴道炎诱导的宫颈阴道上皮细胞凋亡及其信号通路
To elucidate the roles of metalloproteinases and the Bcl-2 family of proteins in Trichovaginalis. vaginalis-induced apoptosis in human cervical cancer cells (SiHa cells) and vaginal epithelial cells (MS74 cells), SiHa cells and MS74 cells were incubated with live T. vaginalis, T. vaginalis excretory and secretory products (ESP), and T. vaginalis lysates, either with or without the specific metalloproteinase inhibitor 1,10-phenanthroline (1,10-PT), and examined apoptotic events and Bcl-2 signaling. The live T. vaginalis and the T. vaginalis ESP induced the release of cytochrome c into the cytosol, the activation of caspase-3 and caspase-9, and the cleavage of PARP. Additionally, the live T. vaginalis, but not the T. vaginalis lysate, induced the cleavage of the proapoptotic Bim protein. The live T. vaginalis and the T. vaginalis ESP, but not the T. vaginalis lysate, induced the dose-dependent cleavage of the antiapoptotic Bcl-xL and Mcl-1 proteins and decreased the association levels of Bcl-xL/Bim and Mcl-1/Bim complexes. We performed gelatin zymography and casein-hydrolysis assays on the live T. vaginalis and the T. vaginalis ESP to identify the apoptosis-inducing factor. Both the live T. vaginalis and the ESP contained high levels of metalloproteinases, of which activities were significantly inhibited by 1,10-PT treatment. Furthermore, the 1,10-PT blocked the cleavage of Bcl-xL, Mcl-1, PARP, caspase-3, and caspase-9, as well as the release of cytochrome c into the cytosol, and it significantly increased the association levels of the Bcl-xL/Bim and Mcl-1/Bim protein complexes, returning them to normal levels. Our results demonstrate that T. vaginalis induces mitochondria-dependent apoptosis in SiHa cells through the dissociation of Bcl-xL/Bim and Mcl-1/Bim complexes and that the apoptosis is blocked by the metalloproteinase inhibitor 1,10-PT. These results expand our understanding of the role of metalloproteinases in T. vaginalis-induced apoptosis and the signaling pathway in trichomoniasis of the cervicovaginal epithelial cells.