Oxidative stress induced by potassium bromate exposure results in altered tight junction protein expression in renal proximal tubule cells

Alice Limonciel, Anja Wilmes, Lydia Aschauer, Robert Radford, Katarzyna M Bloch, Tara McMorrow, Walter Pfaller, Joost H van Delft, Craig Slattery, Michael P Ryan, Edward A Lock, Paul Jennings

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Potassium bromate (KBrO(3)) is an oxidising agent that has been widely used in the food and cosmetic industries. It has shown to be both a nephrotoxin and a renal carcinogen in in vivo and in vitro models. Here, we investigated the effects of KBrO(3) in the human and rat proximal tubular cell lines RPTEC/TERT1 and NRK-52E. A genome-wide transcriptomic screen was carried out from cells exposed to a sub-lethal concentration of KBrO(3) for 6, 24 and 72 h. Pathway analysis identified "glutathione metabolism", "Nrf2-mediated oxidative stress" and "tight junction (TJ) signalling" as the most enriched pathways. TJ signalling was less impacted in the rat model, and further studies revealed low transepithelial electrical resistance (TEER) and an absence of several TJ proteins in NRK-52E cells. In RPTEC/TERT1 cells, KBrO(3) exposure caused a decrease in TEER and resulted in altered expression of several TJ proteins. N-Acetylcysteine co-incubation prevented these effects. These results demonstrate that oxidative stress has, in conjunction with the activation of the cytoprotective Nrf2 pathway, a dramatic effect on the expression of tight junction proteins. The further understanding of the cross-talk between these two pathways could have major implications for epithelial repair, carcinogenesis and metastasis.

Original languageEnglish
Pages (from-to)1741-51
Number of pages11
JournalArchives of Toxicology
Volume86
Issue number11
DOIs
Publication statusPublished - Nov 2012

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Keywords

  • Animals
  • Bromates
  • Cell Line
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation
  • Humans
  • Kidney Tubules, Proximal
  • NF-E2-Related Factor 2
  • Oxidative Stress
  • Rats
  • Tight Junction Proteins
  • Tight Junctions
  • Toxicity Tests
  • Journal Article
  • Research Support, Non-U.S. Gov't

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