Apoptosis of cholangiocytes modulated by thioredoxin of carcinogenic liver fluke

Pitchaya Matchimakul, Gabriel Rinaldi, Sutas Suttiprapa, Victoria H. Mann, Anastas Popratiloff, Thewarach Laha, Rafael N. Pimenta, Christina J. Cochran, Sasithorn Kaewkes, Banchob Sripa*, Paul J. Brindley

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (SciVal)

Abstract

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.

Original languageEnglish
Pages (from-to)72-80
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume65
Early online date23 May 2015
DOIs
Publication statusPublished - 10 Jun 2015
Externally publishedYes

Keywords

  • Apoptosis
  • Apoptosis signal-regulating kinase-1
  • Carcinogenesis
  • Cholangiocyte
  • Gene arrays
  • Liver fluke
  • Opisthorchis viverrini
  • Oxidative stress
  • Thioredoxin
  • xCELLigence
  • Oxidative Stress/physiology
  • Cell Line
  • Opisthorchis/metabolism
  • Humans
  • Thioredoxins/metabolism
  • Animals
  • Apoptosis/physiology
  • Bile Ducts/parasitology
  • Mice
  • Opisthorchiasis/metabolism

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