Oxidative stress induced by potassium bromate exposure results in altered tight junction protein expression in renal proximal tubule cells
- 904 Downloads
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.
KeywordsNrf2 KBrO3 Proximal tubule Claudin Tight junction
This study was funded primarily by the 6th EU Framework project carcinoGENOMICS (Vinken et al. 2008) (to PJ, EAL and MPR) and in part by the 7th EU Framework project Predict-IV (to PJ and WP).
Conflict of interest
The authors declare that they have no conflict of interest.
- Hahn H, Huck CW, Rainer M et al (2007) Analysis of glutathione in supernatants and lysates of a human proximal tubular cell line from perfusion culture upon intoxication with cadmium chloride by HPLC and LC-ESI-MS. Anal Bioanal Chem 388(8):1763–1769. doi: 10.1007/s00216-007-1401-1 PubMedCrossRefGoogle Scholar
- IARC (1999) IARC monographs on the evaluation of carcinogenic risks to humans, vol 43, pp 481–496Google Scholar