pH-Dependent Protein Binding Properties of Uremic Toxins In Vitro.
pH-Dependent Protein Binding Properties of Uremic Toxins In Vitro.
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尿毒症毒素的体外pH依赖性蛋白结合特性。
DOI：
10.3390/toxins13020116
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发表时间：
2021-02-04
期刊：
影响因子：
4.2
通讯作者：
Narita I
中科院分区：
文献类型：
--
作者：
Yamamoto S;Sasahara K;Domon M;Yamaguchi K;Ito T;Goto S;Goto Y;Narita I
蛋白结合尿毒症毒素（PBUT）由于其高蛋白结合亲和力而难以使用常规透析治疗去除。由于pH值改变蛋白质的构象，它可能与尿毒症毒素的结合有关。使用圆二色性分析pH 2至13下的白蛋白构象。采用等温滴定量热法研究了硫酸吲哚酚（IS）与白蛋白的结合行为。将含有IS的白蛋白和含有IS、对甲苯基硫酸盐、吲哚乙酸或苯硫酸盐的血清以及来自血液透析患者的血清的pH调节为3至11，并使用质谱法测量游离PBUT的浓度。白蛋白在pH 12时展开< 4 or >，在pH 10时与IS的相互作用减弱< 5 or >。白蛋白溶液中游离IS的浓度在pH 4.0和pH 11.0时增加。在酸性和碱性pH值下，向每种毒素中加入人血清导致游离形式增加。将血液透析患者血清的pH值调整至3.4和11.3导致PBUT游离形式的浓度增加。总之，酸性和碱性pH条件改变了白蛋白的构象，削弱了PBUT在体外的蛋白结合性能。
Protein-bound uremic toxins (PBUTs) are difficult to remove using conventional dialysis treatment owing to their high protein-binding affinity. As pH changes the conformation of proteins, it may be associated with the binding of uremic toxins. Albumin conformation at pH 2 to 13 was analyzed using circular dichroism. The protein binding behavior between indoxyl sulfate (IS) and albumin was examined using isothermal titration calorimetry. Albumin with IS, and serum with IS, p-cresyl sulfate, indole acetic acid or phenyl sulfate, as well as serum from hemodialysis patients, were adjusted pH of 3 to 11, and the concentration of the free PBUTs was measured using mass spectrometry. Albumin was unfolded at pH < 4 or >12, and weakened interaction with IS occurred at pH < 5 or >10. The concentration of free IS in the albumin solution was increased at pH 4.0 and pH 11.0. Addition of human serum to each toxin resulted in increased free forms at acidic and alkaline pH. The pH values of serums from patients undergoing hemodialysis adjusted to 3.4 and 11.3 resulted in increased concentrations of the free forms of PBUTs. In conclusion, acidic and alkaline pH conditions changed the albumin conformation and weakened the protein binding property of PBUTs in vitro.
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影响因子：
4.6
作者：
Yamamoto S;Kazama JJ;Omori K;Matsuo K;Takahashi Y;Kawamura K;Matsuto T;Watanabe H;Maruyama T;Narita I
通讯作者：
Narita I
影响因子：
3.9
作者：
Deltombe, Olivier;de Loor, Henriette;Eloot, Sunny
通讯作者：
Eloot, Sunny
用于去除人血浆中蛋白质结合毒素的混合基质中空纤维膜
影响因子：
14
作者：
Tijink, Marlon S. L.;Wester, Maarten;Stamatialis, Dimitrios
通讯作者：
Stamatialis, Dimitrios
影响因子：
5.6
作者：
Ghuman, J;Zunszain, PA;Curry, S
通讯作者：
Curry, S
影响因子：
2.6
作者：
Rabbani, Gulam;Ahmad, Ejaz;Khan, Rizwan Hasan
通讯作者：
Khan, Rizwan Hasan