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pH-Dependent Protein Binding Properties of Uremic Toxins In Vitro.
Toxins (Basel). 2021 02 04; 13(2)T

Abstract

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.

Authors+Show Affiliations

Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33557434

Citation

Yamamoto, Suguru, et al. "PH-Dependent Protein Binding Properties of Uremic Toxins in Vitro." Toxins, vol. 13, no. 2, 2021.
Yamamoto S, Sasahara K, Domon M, et al. PH-Dependent Protein Binding Properties of Uremic Toxins In Vitro. Toxins (Basel). 2021;13(2).
Yamamoto, S., Sasahara, K., Domon, M., Yamaguchi, K., Ito, T., Goto, S., Goto, Y., & Narita, I. (2021). PH-Dependent Protein Binding Properties of Uremic Toxins In Vitro. Toxins, 13(2). https://doi.org/10.3390/toxins13020116
Yamamoto S, et al. PH-Dependent Protein Binding Properties of Uremic Toxins in Vitro. Toxins (Basel). 2021 02 4;13(2) PubMed PMID: 33557434.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - pH-Dependent Protein Binding Properties of Uremic Toxins In Vitro. AU - Yamamoto,Suguru, AU - Sasahara,Kenichi, AU - Domon,Mio, AU - Yamaguchi,Keiichi, AU - Ito,Toru, AU - Goto,Shin, AU - Goto,Yuji, AU - Narita,Ichiei, Y1 - 2021/02/04/ PY - 2020/12/18/received PY - 2021/01/30/revised PY - 2021/02/01/accepted PY - 2021/2/9/entrez PY - 2021/2/10/pubmed PY - 2021/7/1/medline KW - albumin KW - indoxyl sulfate KW - isothermal titration calorimetry KW - pH KW - uremic toxins JF - Toxins JO - Toxins (Basel) VL - 13 IS - 2 N2 - 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. SN - 2072-6651 UR - https://www.unboundmedicine.com/medline/citation/33557434/pH_Dependent_Protein_Binding_Properties_of_Uremic_Toxins_In_Vitro_ L2 - https://www.mdpi.com/resolver?pii=toxins13020116 DB - PRIME DP - Unbound Medicine ER -