Interaction of 2′R-ochratoxin A with Serum Albumins: Binding Site, Effects of Site Markers, Thermodynamics, Species Differences of Albumin-binding, and Influence of Albumin on Its Toxicity in MDCK Cells
Ochratoxin A (OTA) is a nephrotoxic mycotoxin. Roasting of OTA-contaminated coffee results in the formation of 2′R-ochratoxin A (2′R-OTA), which appears in the blood of coffee drinkers. Human serum albumin (HSA) binds 2′R-OTA (and OTA) with high affinity; therefore, alb...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-09-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/10/9/353 |
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| author | Zelma Faisal Diána Derdák Beáta Lemli Sándor Kunsági-Máté Mónika Bálint Csaba Hetényi Rita Csepregi Tamás Kőszegi Franziska Sueck Benedikt Cramer Hans-Ulrich Humpf Miklós Poór |
| author_facet | Zelma Faisal Diána Derdák Beáta Lemli Sándor Kunsági-Máté Mónika Bálint Csaba Hetényi Rita Csepregi Tamás Kőszegi Franziska Sueck Benedikt Cramer Hans-Ulrich Humpf Miklós Poór |
| author_sort | Zelma Faisal |
| collection | DOAJ |
| description | Ochratoxin A (OTA) is a nephrotoxic mycotoxin. Roasting of OTA-contaminated coffee results in the formation of 2′R-ochratoxin A (2′R-OTA), which appears in the blood of coffee drinkers. Human serum albumin (HSA) binds 2′R-OTA (and OTA) with high affinity; therefore, albumin may influence the tissue uptake and elimination of ochratoxins. We aimed to investigate the binding site of 2′R-OTA (verses OTA) in HSA and the displacing effects of site markers to explore which molecules can interfere with its albumin-binding. Affinity of 2′R-OTA toward albumins from various species (human, bovine, porcine and rat) was tested to evaluate the interspecies differences regarding 2′R-OTA-albumin interaction. Thermodynamic studies were performed to give a deeper insight into the molecular background of the complex formation. Besides fluorescence spectroscopic and modeling studies, effects of HSA, and fetal bovine serum on the cytotoxicity of 2′R-OTA and OTA were tested in MDCK kidney cell line in order to demonstrate the influence of albumin-binding on the cellular uptake of ochratoxins. Site markers displaced more effectively 2′R-OTA than OTA from HSA. Fluorescence and binding constants of 2′R-OTA-albumin and OTA-albumin complexes showed different tendencies. Albumin significantly decreased the cytotoxicity of ochratoxins. 2′R-OTA, even at sub-toxic concentrations, increased the toxic action of OTA. |
| first_indexed | 2024-04-13T07:06:54Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-13T07:06:54Z |
| publishDate | 2018-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-98c906e3423d484588fd618f601da6ee2022-12-22T02:56:58ZengMDPI AGToxins2072-66512018-09-0110935310.3390/toxins10090353toxins10090353Interaction of 2′R-ochratoxin A with Serum Albumins: Binding Site, Effects of Site Markers, Thermodynamics, Species Differences of Albumin-binding, and Influence of Albumin on Its Toxicity in MDCK CellsZelma Faisal0Diána Derdák1Beáta Lemli2Sándor Kunsági-Máté3Mónika Bálint4Csaba Hetényi5Rita Csepregi6Tamás Kőszegi7Franziska Sueck8Benedikt Cramer9Hans-Ulrich Humpf10Miklós Poór11Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryJános Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, HungaryJános Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, HungaryJános Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryJános Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, HungaryJános Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, HungaryInstitute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstr. 45, 48149 Münster, GermanyInstitute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstr. 45, 48149 Münster, GermanyInstitute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstr. 45, 48149 Münster, GermanyDepartment of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryOchratoxin A (OTA) is a nephrotoxic mycotoxin. Roasting of OTA-contaminated coffee results in the formation of 2′R-ochratoxin A (2′R-OTA), which appears in the blood of coffee drinkers. Human serum albumin (HSA) binds 2′R-OTA (and OTA) with high affinity; therefore, albumin may influence the tissue uptake and elimination of ochratoxins. We aimed to investigate the binding site of 2′R-OTA (verses OTA) in HSA and the displacing effects of site markers to explore which molecules can interfere with its albumin-binding. Affinity of 2′R-OTA toward albumins from various species (human, bovine, porcine and rat) was tested to evaluate the interspecies differences regarding 2′R-OTA-albumin interaction. Thermodynamic studies were performed to give a deeper insight into the molecular background of the complex formation. Besides fluorescence spectroscopic and modeling studies, effects of HSA, and fetal bovine serum on the cytotoxicity of 2′R-OTA and OTA were tested in MDCK kidney cell line in order to demonstrate the influence of albumin-binding on the cellular uptake of ochratoxins. Site markers displaced more effectively 2′R-OTA than OTA from HSA. Fluorescence and binding constants of 2′R-OTA-albumin and OTA-albumin complexes showed different tendencies. Albumin significantly decreased the cytotoxicity of ochratoxins. 2′R-OTA, even at sub-toxic concentrations, increased the toxic action of OTA.http://www.mdpi.com/2072-6651/10/9/3532′R-ochratoxin Aochratoxin Aserum albuminalbumin-ligand interactionspecies differencescellular toxicity |
| spellingShingle | Zelma Faisal Diána Derdák Beáta Lemli Sándor Kunsági-Máté Mónika Bálint Csaba Hetényi Rita Csepregi Tamás Kőszegi Franziska Sueck Benedikt Cramer Hans-Ulrich Humpf Miklós Poór Interaction of 2′R-ochratoxin A with Serum Albumins: Binding Site, Effects of Site Markers, Thermodynamics, Species Differences of Albumin-binding, and Influence of Albumin on Its Toxicity in MDCK Cells Toxins 2′R-ochratoxin A ochratoxin A serum albumin albumin-ligand interaction species differences cellular toxicity |
| title | Interaction of 2′R-ochratoxin A with Serum Albumins: Binding Site, Effects of Site Markers, Thermodynamics, Species Differences of Albumin-binding, and Influence of Albumin on Its Toxicity in MDCK Cells |
| title_full | Interaction of 2′R-ochratoxin A with Serum Albumins: Binding Site, Effects of Site Markers, Thermodynamics, Species Differences of Albumin-binding, and Influence of Albumin on Its Toxicity in MDCK Cells |
| title_fullStr | Interaction of 2′R-ochratoxin A with Serum Albumins: Binding Site, Effects of Site Markers, Thermodynamics, Species Differences of Albumin-binding, and Influence of Albumin on Its Toxicity in MDCK Cells |
| title_full_unstemmed | Interaction of 2′R-ochratoxin A with Serum Albumins: Binding Site, Effects of Site Markers, Thermodynamics, Species Differences of Albumin-binding, and Influence of Albumin on Its Toxicity in MDCK Cells |
| title_short | Interaction of 2′R-ochratoxin A with Serum Albumins: Binding Site, Effects of Site Markers, Thermodynamics, Species Differences of Albumin-binding, and Influence of Albumin on Its Toxicity in MDCK Cells |
| title_sort | interaction of 2 r ochratoxin a with serum albumins binding site effects of site markers thermodynamics species differences of albumin binding and influence of albumin on its toxicity in mdck cells |
| topic | 2′R-ochratoxin A ochratoxin A serum albumin albumin-ligand interaction species differences cellular toxicity |
| url | http://www.mdpi.com/2072-6651/10/9/353 |
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