Apoptosis of cholangiocytes modulated by thioredoxin of carcinogenic liver fluke.
Apoptosis of cholangiocytes modulated by thioredoxin of carcinogenic liver fluke.
复制标题
胆管细胞的凋亡是由致癌性肝氟硫氧还蛋白调节的。
DOI：
10.1016/j.biocel.2015.05.014
复制
发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Brindley PJ
中科院分区：
文献类型：
--
作者：
Matchimakul P;Rinaldi G;Suttiprapa S;Mann VH;Popratiloff A;Laha T;Pimenta RN;Cochran CJ;Kaewkes S;Sripa B;Brindley PJ
食源性肝吸虫（猫尾后睾吸虫）的慢性感染常导致胆管癌、胆管癌。后睾吸虫病在泰国、老挝人民民主共和国、柬埔寨和越南流行，在这些国家，食用携带这种病原体幼年期的未煮熟的淡水鱼会导致人类感染。由于细胞凋亡的抑制促进癌的发生，本研究探讨了硫氧还蛋白从O。胆管上皮细胞、胆管细胞凋亡。将胆管细胞系的细胞与寄生虫酶一起孵育，之后将它们暴露于过氧化氢。氧化应激诱导的细胞凋亡，监测使用流式细胞术，生长在真实的时间和成像的活细胞，使用激光共聚焦显微镜。免疫定位显示肝吸虫硫氧还蛋白内胆管细胞。硫氧还蛋白可下调丝裂原活化蛋白激酶途径中的凋亡基因，上调凋亡信号激酶1、caspase 9、caspase 8、caspase 3、survivin等抗凋亡相关基因。细胞裂解物的免疫沉淀物的Western印迹显示硫氧还蛋白与凋亡信号激酶1的结合。这些结果表明O.小灵猫抑制氧化应激诱导的胆管上皮细胞凋亡，这支持了这种肝吸虫氧化还原酶在后睾吸虫病诱导的胆管癌发生中的作用。硫氧还蛋白对猫尾睾吸虫胆管细胞凋亡的影响
Chronic infection the food-borne liver fluke, Opisthorchis viverrini, frequently induces cancer of the bile ducts, cholangiocarcinoma. Opisthorchiasis is endemic in Thailand, Lao PDR, Cambodia and Vietnam, where eating undercooked freshwater fish carrying the juvenile stage of this pathogen leads to human infection. Because inhibition of apoptosis facilitates carcinogenesis, this study investigated modulation by thioredoxin from O. viverrini of apoptosis of bile duct epithelial cells, cholangiocytes. Cells of a cholangiocyte line were incubated with the parasite enzyme after which they were exposed hydrogen peroxide. Oxidative stress-induced apoptosis was monitored using flow cytometry, growth in real time and imaging of living cells using laser confocal microscopy. Immunolocalization revealed liver fluke thioredoxin within cholangiocytes. Cells exposed to thioredoxin downregulated apoptotic genes in the mitogen activated protein kinases pathway and upregulated anti-apoptosis-related genes including apoptosis signaling kinase 1, caspase 9, caspase 8, caspase 3, survivin and others. Western blots of immunoprecipitates of cell lysates revealed binding of thioredoxin to apoptosis signaling kinase 1. Together the findings indicated that thioredoxin from O. viverrini inhibited oxidative stress-induced apoptosis of bile duct epithelial cells, which supports a role for this liver fluke oxidoreductase in opisthorchiasis-induced cholangiocarcinogenesis. Apoptosis of cholangiocytes modulated by thioredoxin from Opisthorchis viverrini