Document Detail


Oxidative stress induced by potassium bromate exposure results in altered tight junction protein expression in renal proximal tubule cells.
MedLine Citation:
PMID:  22760423     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
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
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-4
Journal Detail:
Title:  Archives of toxicology     Volume:  -     ISSN:  1432-0738     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417615     Medline TA:  Arch Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University, Fritz-Pregl Strasse 3/1, 6020, Innsbruck, Austria.
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