title: Effect of heme oxygenase-1 on ochratoxin A-induced nephrotoxicity in mice.
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.
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland. Electronic address: agnieszka.loboda@uj.edu.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Loboda
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Stachurska
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Podkalicka
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Sobczak
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Mucha
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Witalisz-Siepracka
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Jozkowicz
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Jozef
authors.initials: J
authors.lastname: Dulak
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D018374:LLC-PK1 Cells; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009793:Ochratoxins / Q000633:toxicity*; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013552:Swine
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008565:Membrane Proteins; D009793:Ochratoxins; D011524:Protoporphyrins; D012333:RNA, Messenger; C025589:ochratoxin A; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Heme oxygenase-1; Kidney; Nephrotoxicity; Ochratoxin A; microRNA