Effect of heme oxygenase-1 on ochratoxin A-induced nephrotoxicity in mice

Agnieszka Loboda*, Anna Stachurska, Paulina Podkalicka, Mateusz Sobczak, Olga Mucha, Agnieszka Witalisz-Siepracka, Alicja Jozkowicz, Jozef Dulak

*Corresponding author for this work

Research output: Journal article (peer-reviewed)Journal article

30 Citations (Scopus)

Abstract

Heme oxygenase-1 (HO-1), a heme-degrading enzyme, is suggested to play an important role in kidney pathophysiology, mostly due to its anti-fibrotic, anti-apoptotic and anti-oxidant properties. One of the mycotoxin, ochratoxin A (OTA) was previously shown to affect HO-1 expression, however, the mechanisms of OTA-induced nephrotoxicity during HO-1 deficiency are unknown. We have shown that OTA regulates the number of pro-fibrotic, pro-inflammatory, anti-oxidative and pro-apoptotic factors in HO-1 dependent manner, as the lack of HO-1 accelerates whereas the induction of HO-1 expression by cobalt protoporphyrin (CoPP) attenuates nephrotoxic effect of OTA. The down-regulation of the nuclear factor-erythroid-2- related factor 2 (Nrf2) transcription factor by OTA, observed in HO-1 knock-out animals, might be another mechanism of OTA toxicity. Moreover, HO-1 level and OTA treatment influences the expression of microRNAs. Namely, p53-regulated miR-34a and pro-fibrotic miR-21 were already increased in HO-1−/− kidneys and were further induced by OTA administration, whereas anti-fibrotic miR-29c was down-regulated by this mycotoxin. Our study indicates that complex mechanisms of OTA nephrotoxicity may be partially overcome by HO-1 induction.

Original languageEnglish
Pages (from-to)46-57
Number of pages12
JournalInternational Journal of Biochemistry and Cell Biology
Volume84
DOIs
Publication statusPublished - 01 Mar 2017
Externally publishedYes

Keywords

  • Heme oxygenase-1
  • Kidney
  • microRNA
  • Nephrotoxicity
  • Ochratoxin A

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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