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Mass Spectrometric and Spectrofluorometric Studies of the Interaction of Aristolochic Acids with Proteins

Aristolochic acid (AA) is a potent carcinogen and nephrotoxin and is associated with the development of “Chinese herb nephropathy” and Balkan endemic nephropathy. Despite decades of research, the specific mechanism of the observed nephrotoxicity has remained elusive and the potential effects on prot...

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Autores principales: Li, Weiwei, Hu, Qin, Chan, Wan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608009/
https://www.ncbi.nlm.nih.gov/pubmed/26471474
http://dx.doi.org/10.1038/srep15192
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author Li, Weiwei
Hu, Qin
Chan, Wan
author_facet Li, Weiwei
Hu, Qin
Chan, Wan
author_sort Li, Weiwei
collection PubMed
description Aristolochic acid (AA) is a potent carcinogen and nephrotoxin and is associated with the development of “Chinese herb nephropathy” and Balkan endemic nephropathy. Despite decades of research, the specific mechanism of the observed nephrotoxicity has remained elusive and the potential effects on proteins due to the observed toxicity of AA are not well-understood. To better understand the pharmacotoxicological features of AA, we investigated the non-covalent interactions of AA with proteins. The protein-binding properties of AA with bovine serum albumin (BSA) and lysozyme were characterized using spectrofluorometric and mass spectrometric (MS) techniques. Moreover, the protein-AA complexes were clearly identified by high-resolution MS analyses. To the best of our knowledge, this is the first direct evidence of non-covalently bound protein-AA complexes. An analysis of the spectrofluorometric data by a modified Stern−Volmer plot model also revealed that both aristolochic acid I (AAI) and aristolochic acid II (AAII) were bound to BSA and lysozyme in 1:1 stoichiometries. A significantly stronger protein binding property was observed in AAII than in AAI as evidenced by the spectrofluorometric and MS analyses, which may explain the observed higher mutagenicity of AAII.
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spelling pubmed-46080092015-10-28 Mass Spectrometric and Spectrofluorometric Studies of the Interaction of Aristolochic Acids with Proteins Li, Weiwei Hu, Qin Chan, Wan Sci Rep Article Aristolochic acid (AA) is a potent carcinogen and nephrotoxin and is associated with the development of “Chinese herb nephropathy” and Balkan endemic nephropathy. Despite decades of research, the specific mechanism of the observed nephrotoxicity has remained elusive and the potential effects on proteins due to the observed toxicity of AA are not well-understood. To better understand the pharmacotoxicological features of AA, we investigated the non-covalent interactions of AA with proteins. The protein-binding properties of AA with bovine serum albumin (BSA) and lysozyme were characterized using spectrofluorometric and mass spectrometric (MS) techniques. Moreover, the protein-AA complexes were clearly identified by high-resolution MS analyses. To the best of our knowledge, this is the first direct evidence of non-covalently bound protein-AA complexes. An analysis of the spectrofluorometric data by a modified Stern−Volmer plot model also revealed that both aristolochic acid I (AAI) and aristolochic acid II (AAII) were bound to BSA and lysozyme in 1:1 stoichiometries. A significantly stronger protein binding property was observed in AAII than in AAI as evidenced by the spectrofluorometric and MS analyses, which may explain the observed higher mutagenicity of AAII. Nature Publishing Group 2015-10-16 /pmc/articles/PMC4608009/ /pubmed/26471474 http://dx.doi.org/10.1038/srep15192 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Li, Weiwei
Hu, Qin
Chan, Wan
Mass Spectrometric and Spectrofluorometric Studies of the Interaction of Aristolochic Acids with Proteins
title Mass Spectrometric and Spectrofluorometric Studies of the Interaction of Aristolochic Acids with Proteins
title_full Mass Spectrometric and Spectrofluorometric Studies of the Interaction of Aristolochic Acids with Proteins
title_fullStr Mass Spectrometric and Spectrofluorometric Studies of the Interaction of Aristolochic Acids with Proteins
title_full_unstemmed Mass Spectrometric and Spectrofluorometric Studies of the Interaction of Aristolochic Acids with Proteins
title_short Mass Spectrometric and Spectrofluorometric Studies of the Interaction of Aristolochic Acids with Proteins
title_sort mass spectrometric and spectrofluorometric studies of the interaction of aristolochic acids with proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608009/
https://www.ncbi.nlm.nih.gov/pubmed/26471474
http://dx.doi.org/10.1038/srep15192
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