Ochratoxin A impairs Nrf2-dependent gene expression in porcine kidney tubulus cells

Boesch-Saadatmandi, C., Wagner, A. E., Graeser, A. C., Hundhausen, C., Wolffram, S. and Rimbach, Gerald (2009) Ochratoxin A impairs Nrf2-dependent gene expression in porcine kidney tubulus cells Journal of Animal Physiology and Animal Nutrition, 93 (5). pp. 547-554.

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Abstract

P>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.

Document Type: Article
Keywords: ochratoxin anrf2-dependent gene expression kidney pig antioxidant response element transcription factor nrf2 oxidative stress inducible expression keap1 nephropathy degradation induction toxicity factor-2
Research affiliation: Kiel University
OceanRep > The Future Ocean - Cluster of Excellence
Refereed: Yes
ISSN: 0931-2439
Projects: Future Ocean
Date Deposited: 11 Feb 2011 12:16
Last Modified: 09 Jun 2017 12:33
URI: http://eprints.uni-kiel.de/id/eprint/9300

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