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Ochratoxin A impairs Nrf2 dependent signal transduction pathways in porcine kidney tubulus cells

Lookup NU author(s): Dr Christine Bosch-Saadatmandi

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Abstract

The mycotoxin, ochratoxin A (OTA), which is produced by Aspergillus and Penicillium subspecies, is frequently present in feedstuffs. Ochratoxin A exhibits a wide range of toxic activities including nephrotoxicity. However, the underlying molecular mechanisms of OTA-induced cellular nephrotoxicity have yet not been fully elucidated. Nrf2 is a basic leucine zipper transcriptional activator essential for the coordinated transcriptional induction of antioxidant and xenobiotic metabolizing enzymes in the kidney. Therefore, in the present study, the effects of OTA on the nuclear translocation and transactivation of the transcription factor Nrf2 as well as mRNA levels of Nrf2 target genes including glutathione-S-transferase and gamma-glutamylcysteinyl synthetase have been studied in cultured porcine kidney tubulus cells (LLC-PK1). Nrf2 was induced by sulforaphane, a well-known activator of this transcription factor. Ochratoxin A significantly decreased gamma-glutamylcysteinyl synthetase and glutathione-S-transferase mRNA levels in LLC-PK1 cells. Decreased mRNA levels of gamma-glutamylcysteinyl synthetase and glutathione-S-transferase were accompanied by a lowered nuclear translocation and transactivation of Nrf2. Furthermore, OTA also lowered Nrf2 mRNA levels. Current data indicate that OTA nephrotoxicity may be, at least partly, mediated by an Nrf2-dependent signal transduction pathway.

Publication metadata

Author(s): Boesch-Saadatmandi C, Wagner AE, Graeser AC, Hundhausen C, Wolffram S, Rimbach G

Publication type: Article

Publication status: Published

Journal: Journal of Animal Physiology and Animal Nutrition

Year: 2009

Volume: 96

Issue: 5

Pages: 547-554

ISSN (print): 0931-2439

ISSN (electronic): 1439-0396

Publisher: Wiley-Blackwell Verlag GmbH

URL: http://dx.doi.org/10.1111/j.1439-0396.2008.00838.x

DOI: 10.1111/j.1439-0396.2008.00838.x

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