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2'-羟基 ochratoxin A 与血清白蛋白的相互作用：结合部位、位点标记物的影响、热力学、白蛋白结合的种属差异，以及白蛋白对其在 MDCK 细胞中毒性的影响。

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.

机构信息

Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary.

János Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary.

出版信息

Toxins (Basel). 2018 Sep 1;10(9):353. doi: 10.3390/toxins10090353.

DOI:10.3390/toxins10090353
PMID:30200461
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6162703/
Abstract

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.

摘要

赭曲霉毒素 A（OTA）是一种肾毒性真菌毒素。OTA 污染咖啡的烘焙会导致 2'R-ochratoxin A（2'R-OTA）的形成，这种物质会出现在喝咖啡的人的血液中。人血清白蛋白（HSA）与 2'R-OTA（和 OTA）具有高亲和力结合；因此，白蛋白可能会影响真菌毒素在组织中的摄取和消除。我们旨在研究 2'R-OTA（与 OTA 相比）在 HSA 中的结合部位，以及位点标记物的置换效应，以探索哪些分子可以干扰其与白蛋白的结合。测试了来自不同物种（人、牛、猪和大鼠）的白蛋白与 2'R-OTA 的亲和力，以评估 2'R-OTA-白蛋白相互作用的种间差异。进行热力学研究以更深入地了解复合物形成的分子背景。除了荧光光谱学和建模研究外，还在 MDCK 肾细胞系中测试了 HSA 和胎牛血清对 2'R-OTA 和 OTA 细胞毒性的影响，以证明白蛋白结合对真菌毒素细胞摄取的影响。位点标记物从 HSA 中更有效地置换了 2'R-OTA 而不是 OTA。2'R-OTA-白蛋白和 OTA-白蛋白复合物的荧光和结合常数显示出不同的趋势。白蛋白显著降低了真菌毒素的细胞毒性。即使在亚毒性浓度下，2'R-OTA 也会增加 OTA 的毒性作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a6d/6162703/7844ec44e395/toxins-10-00353-g010.jpg
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