title: Disturbed Hsp70 and Hsp27 expression and thiol redox status in porcine kidney PK15 cells provoked by individual and combined ochratoxin A and citrinin treatments.
abstract: The aim of this study was to explore the oxidative properties of ochratoxin A (OTA) and citrinin (CTN) as a possible underlying mechanism of their individual and/or combined cytotoxicity. Metabolic activity of PK15 porcine kidney cells was significantly reduced with OTA and CTN co-exposures, with synergistic cytotoxic interactions. Single CTN increased both reduced (GSH) and oxidized (GSSG) glutathione after 24 h. However, GSH was significantly lowered with all OTA and CTN combined applications in synergistic manner after 12 and 24 h. GSH/GSSG ratio was reduced in most single and dual treatments, which suggested the presence of oxidative stress. In addition, OTA and CTN exposures significantly decreased concentrations of total thiols, with mycotoxins interactions being synergistic or antagonistic. The expression levels of Hsps were differentially affected by single and dual mycotoxin(s) applications. Single OTA provoked significant down-regulation of Hsp70 and Hsp27 expressions, while CTN stimulated Hsps expressions. Hsps were also up-regulated by dual treatments, and this induction was much stronger then with single CTN. In conclusion, significant alterations in cellular redox status (glutathione, thiols) and protective mechanisms (Hsps) suggest that those disturbances might be involved in OTA and CTN individual and combined mechanisms of cytotoxicity.
authors.affiliation: Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
authors.forename: Maja
authors.initials: M
authors.lastname: Segvić Klarić
authors.affiliation: Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
authors.forename: Nevena
authors.initials: N
authors.lastname: Medić
authors.affiliation: Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hulina
authors.affiliation: Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
authors.forename: Tihana
authors.initials: T
authors.lastname: Zanić Grubišić
authors.affiliation: Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia. Electronic address: lrumora@pharma.hr.
authors.forename: Lada
authors.initials: L
authors.lastname: Rumora
mesh_terms: D000818:Animals; D002460:Cell Line; D002953:Citrinin / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009793:Ochratoxins / Q000633:toxicity*; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D009793:Ochratoxins; D013438:Sulfhydryl Compounds; C025589:ochratoxin A; D002953:Citrinin; D005978:Glutathione
keywords: Citrinin; Glutathione; Heat shock proteins; Ochratoxin A; Oxidative stress; PK15 cells