2. Academic Validation
  3. Interaction of Mycotoxin Alternariol with Serum Albumin

Interaction of Mycotoxin Alternariol with Serum Albumin

  • Int J Mol Sci. 2019 May 12;20(9):2352. doi: 10.3390/ijms20092352.
Eszter Fliszár-Nyúl 1 2,  Beáta Lemli 3 4,  Sándor Kunsági-Máté 5 6,  Luca Dellafiora 7,  Chiara Dall'Asta 8,  Gabriele Cruciani 9,  Gábor Pethő 10 11,  Miklós Poór 12 13
Affiliations

Affiliations

  • 1 Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, H-7642 Pécs; Hungary. [email protected].
  • 2 János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7642 Pécs; Hungary. [email protected].
  • 3 János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7642 Pécs; Hungary. [email protected].
  • 4 Institute of Organic and Medicinal Chemistry, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary. [email protected].
  • 5 János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7642 Pécs; Hungary. [email protected].
  • 6 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Pécs, Rókus utca 2, H-7642 Pécs, Hungary. [email protected].
  • 7 Department of Food and Drug, University of Parma, Via G.P. 7 Usberti 17/A, 43124 Parma, Italy. [email protected].
  • 8 Department of Food and Drug, University of Parma, Via G.P. 7 Usberti 17/A, 43124 Parma, Italy. [email protected].
  • 9 Department of Chemistry, Biology and Biotechnology, University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy. [email protected].
  • 10 Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, H-7642 Pécs; Hungary. [email protected].
  • 11 Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary. [email protected].
  • 12 Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, H-7642 Pécs; Hungary. [email protected].
  • 13 János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7642 Pécs; Hungary. [email protected].
PMID: 31083629 DOI: 10.3390/ijms20092352
Abstract

Alternariol (AOH) is a mycotoxin produced by Alternaria species. In vitro studies suggest the genotoxic, mutagenic, and endocrine disruptor effects of AOH, and an increased incidence of esophageal Cancer has been reported related to higher AOH exposure. Human serum albumin (HSA) is the most abundant plasma protein in the circulation, it is able to affect toxicokinetic properties of numerous xenobiotics. HSA forms stable complexes with several mycotoxins, however, the interaction of AOH with albumin has not been examined. In this study, the complex formation of AOH with HSA was tested, employing fluorescence spectroscopy, ultrafiltration, and molecular modeling. Each spectroscopic measurement shows the formation of stable AOH-HSA complexes (K = 4 × 105 L/mol). Investigations with site markers (in spectroscopic and ultrafiltration models) as well as modeling studies suggest that AOH occupies Sudlow's site I as a high-affinity binding site in HSA. The binding affinity of AOH towards bovine, porcine, and rat albumins was also tested, suggesting that AOH binds to rat albumin with considerably higher affinity than other albumins tested. Our results demonstrate the strong interaction of AOH with serum albumins, suggesting the potential in vivo importance of these interactions.

Keywords

albumin-ligand interaction; alternariol; binding site; fluorescence spectroscopy; serum albumin.

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