کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1983474 1539879 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Apoptosis of cholangiocytes modulated by thioredoxin of carcinogenic liver fluke
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Apoptosis of cholangiocytes modulated by thioredoxin of carcinogenic liver fluke
چکیده انگلیسی


• Secreted parasite enzyme may contribute to micro-environment conducive to helminth infection-induced carcinogenesis.
• Thrioredoxin-1 from liver fluke modulated oxidative stress-induced apoptosis in human cholangiocytes.
• Liver fluke thioredoxin bound to apoptosis signal-regulating kinase-1.
• Cholangiocytes cultured in liver fluke thioredoxin downregulated apoptotic genes in the MAP3K pathway, and upregulated anti-apoptosis-related genes.

Chronic infection with 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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 65, August 2015, Pages 72–80
نویسندگان
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