Archives of Toxicology

, Volume 86, Issue 11, pp 1741–1751 | Cite as

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
Genotoxicity and Carcinogenicity

Abstract

Potassium bromate (KBrO3) 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 KBrO3 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 KBrO3 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, KBrO3 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.

Keywords

Nrf2 KBrO3 Proximal tubule Claudin Tight junction 

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Alice Limonciel
    • 1
  • Anja Wilmes
    • 1
  • Lydia Aschauer
    • 1
  • Robert Radford
    • 2
  • Katarzyna M. Bloch
    • 3
  • Tara McMorrow
    • 2
  • Walter Pfaller
    • 1
  • Joost H. van Delft
    • 4
  • Craig Slattery
    • 2
  • Michael P. Ryan
    • 2
  • Edward A. Lock
    • 3
  • Paul Jennings
    • 1
  1. 1.Division of Physiology, Department of Physiology and Medical PhysicsInnsbruck Medical UniversityInnsbruckAustria
  2. 2.Renal Disease Research Group, School of Biomolecular and Biomedical Science, UCD Conway InstituteUniversity College DublinDublinIreland
  3. 3.School of Pharmacy and Biomolecular SciencesLiverpool John Moores UniversityLiverpoolUK
  4. 4.Department of Health Risk Analysis and ToxicologyMaastricht UniversityMaastrichtThe Netherlands

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