Caspase-dependent apoptosis of the HCT-8 epithelial cell line induced by the parasite Giardia intestinalis

Caspase-dependent apoptosis of the HCT-8 epithelial cell line induced by the parasite Giardia intestinalis
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DOI:
10.1111/j.1574-695x.2007.00304.x
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发表时间:
2007-11-01
影响因子:
--
通讯作者:
Cavallo, Pasqua
Cavallo, Pasqua
中科院分区:
其他
文献类型:
--
作者:
Panaro, Maria Antonietta;Cianciulli, Antonia;Cavallo, Pasqua

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贾第鞭毛虫是一种有鞭毛的原生动物,在世界范围内引起肠道疾病。贾第虫滋养体感染小肠近端的上皮细胞,可引起急性或慢性腹泻。贾第虫病上皮损伤的机制仍不清楚。许多肠道病原体,包括原生动物寄生虫,能够诱导肠上皮细胞凋亡。这项工作的目的是评估是否G。大肠杆菌WB株克隆C6能够诱导人肠上皮细胞系HCT-8的凋亡,并研究半胱天冬酶在此过程中的作用。结果表明,寄生虫诱导细胞凋亡,如通过DNA片段化分析、活性半胱天冬酶-3的检测和半胱天冬酶-3底物PARP [聚(ADP-核糖)聚合酶]的降解所证实的。此外,G.贾第鞭毛虫感染诱导激活的内在和外在的凋亡途径,下调的抗凋亡蛋白Bcl-2和上调的促凋亡Bax,这表明半胱天冬酶依赖性细胞凋亡在贾第鞭毛虫病的发病机制中可能发挥作用。
Giardia intestinalis is a flagellated protozoan which causes enteric disease worldwide. Giardia trophozoites infect epithelial cells of the proximal small intestine and can cause acute or chronic diarrhea. The mechanism of epithelial injury in giardiasis remains unknown. A number of enteric pathogens, including protozoan parasites, are able to induce enterocyte apoptosis. The aim of this work was to assess whether G. intestinalis strain WB clone C6 is able to induce apoptosis in the human intestinal epithelial cell line HCT-8, and to investigate the role of caspases in this process. Results demonstrated that the parasite induces cell apoptosis, as confirmed by DNA fragmentation analysis, detection of active caspase-3 and degradation of the caspase-3 substrate PARP [poly(ADP-ribose) polymerase]. Furthermore, G. intestinalis infection induces activation of both the intrinsic and the extrinsic apoptotic pathways, down-regulation of the antiapoptotic protein Bcl-2 and up-regulation of the proapoptotic Bax, suggesting a possible role for caspase-dependent apoptosis in the pathogenesis of giardiasis.