title: Oxidative stress induced by potassium bromate exposure results in altered tight junction protein expression in renal proximal tubule cells.
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.
authors: Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University, Fritz-Pregl Strasse 3/1, Innsbruck, Austria.
authors: Alice
authors: A
authors: Limonciel
authors: Anja
authors: A
authors: Wilmes
authors: Lydia
authors: L
authors: Aschauer
authors: Robert
authors: R
authors: Radford
authors: Katarzyna M
authors: KM
authors: Bloch
authors: Tara
authors: T
authors: McMorrow
authors: Walter
authors: W
authors: Pfaller
authors: Joost H
authors: JH
authors: van Delft
authors: Craig
authors: C
authors: Slattery
authors: Michael P
authors: MP
authors: Ryan
authors: Edward A
authors: EA
authors: Lock
authors: Paul
authors: P
authors: Jennings
mesh_terms: D000818:Animals; D001959:Bromates / Q000633:toxicity*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D062725:Tight Junction Proteins / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism; D018675:Toxicity Tests
chemical_list: D001959:Bromates; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495637:Nfe2l2 protein, rat; D062725:Tight Junction Proteins; C019536:potassium bromate