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Serum albumin cysteine trioxidation is a potential oxidative stress biomarker of type 2 diabetes mellitus
Metabolic disorders in T2DM generate multiple sources of free radicals and oxidative stress that accelerate nonenzymatic degenerative protein modifications (DPMs) such as protein oxidation, disrupt redox signaling and physiological function, and remain a major risk factor for clinical diabetic vascu...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160123/ https://www.ncbi.nlm.nih.gov/pubmed/32296090 http://dx.doi.org/10.1038/s41598-020-62341-z |
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author | Paramasivan, Selvam Adav, Sunil S. Ngan, SoFong Cam Dalan, Rinkoo Leow, Melvin Khee-Shing Ho, Hee Hwa Sze, Siu Kwan |
author_facet | Paramasivan, Selvam Adav, Sunil S. Ngan, SoFong Cam Dalan, Rinkoo Leow, Melvin Khee-Shing Ho, Hee Hwa Sze, Siu Kwan |
author_sort | Paramasivan, Selvam |
collection | PubMed |
description | Metabolic disorders in T2DM generate multiple sources of free radicals and oxidative stress that accelerate nonenzymatic degenerative protein modifications (DPMs) such as protein oxidation, disrupt redox signaling and physiological function, and remain a major risk factor for clinical diabetic vascular complications. In order to identify potential oxidative biomarkers in the blood plasma of patients with T2DM, we used LC-MS/MS-based proteomics to profile plasma samples from patients with T2DM and healthy controls. The results showed that human serum albumin (HSA) is damaged by irreversible cysteine trioxidation, which can be a potential oxidative stress biomarker for the early diagnosis of T2DM. The quantitative detection of site-specific thiol trioxidation is technically challenging; thus, we developed a sensitive and selective LC-MS/MS workflow that has been used to discover and quantify three unique thiol-trioxidized HSA peptides, ALVLIAFAQYLQQC((SO3H))PFEDHVK (m/z 1241.13), YIC((SO3H))ENQDSISSK (m/z 717.80) and RPC((SO3H))FSALEVDETYVPK (m/z 951.45), in 16 individual samples of healthy controls (n = 8) and individuals with diabetes (n = 8). Targeted quantitative analysis using multiple reaction monitoring mass spectrometry revealed impairment of the peptides with m/z 1241.13, m/z 717.80 and m/z 951.45, with significance (P < 0.02, P < 0.002 and P < 0.03), in individuals with diabetes. The results demonstrated that a set of three HSA thiol-trioxidized peptides, which are irreversibly oxidatively damaged in HSA in the plasma of patients with T2DM, can be important indicators and potential biomarkers of oxidative stress in T2DM. |
format | Online Article Text |
id | pubmed-7160123 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71601232020-04-22 Serum albumin cysteine trioxidation is a potential oxidative stress biomarker of type 2 diabetes mellitus Paramasivan, Selvam Adav, Sunil S. Ngan, SoFong Cam Dalan, Rinkoo Leow, Melvin Khee-Shing Ho, Hee Hwa Sze, Siu Kwan Sci Rep Article Metabolic disorders in T2DM generate multiple sources of free radicals and oxidative stress that accelerate nonenzymatic degenerative protein modifications (DPMs) such as protein oxidation, disrupt redox signaling and physiological function, and remain a major risk factor for clinical diabetic vascular complications. In order to identify potential oxidative biomarkers in the blood plasma of patients with T2DM, we used LC-MS/MS-based proteomics to profile plasma samples from patients with T2DM and healthy controls. The results showed that human serum albumin (HSA) is damaged by irreversible cysteine trioxidation, which can be a potential oxidative stress biomarker for the early diagnosis of T2DM. The quantitative detection of site-specific thiol trioxidation is technically challenging; thus, we developed a sensitive and selective LC-MS/MS workflow that has been used to discover and quantify three unique thiol-trioxidized HSA peptides, ALVLIAFAQYLQQC((SO3H))PFEDHVK (m/z 1241.13), YIC((SO3H))ENQDSISSK (m/z 717.80) and RPC((SO3H))FSALEVDETYVPK (m/z 951.45), in 16 individual samples of healthy controls (n = 8) and individuals with diabetes (n = 8). Targeted quantitative analysis using multiple reaction monitoring mass spectrometry revealed impairment of the peptides with m/z 1241.13, m/z 717.80 and m/z 951.45, with significance (P < 0.02, P < 0.002 and P < 0.03), in individuals with diabetes. The results demonstrated that a set of three HSA thiol-trioxidized peptides, which are irreversibly oxidatively damaged in HSA in the plasma of patients with T2DM, can be important indicators and potential biomarkers of oxidative stress in T2DM. Nature Publishing Group UK 2020-04-15 /pmc/articles/PMC7160123/ /pubmed/32296090 http://dx.doi.org/10.1038/s41598-020-62341-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Paramasivan, Selvam Adav, Sunil S. Ngan, SoFong Cam Dalan, Rinkoo Leow, Melvin Khee-Shing Ho, Hee Hwa Sze, Siu Kwan Serum albumin cysteine trioxidation is a potential oxidative stress biomarker of type 2 diabetes mellitus |
title | Serum albumin cysteine trioxidation is a potential oxidative stress biomarker of type 2 diabetes mellitus |
title_full | Serum albumin cysteine trioxidation is a potential oxidative stress biomarker of type 2 diabetes mellitus |
title_fullStr | Serum albumin cysteine trioxidation is a potential oxidative stress biomarker of type 2 diabetes mellitus |
title_full_unstemmed | Serum albumin cysteine trioxidation is a potential oxidative stress biomarker of type 2 diabetes mellitus |
title_short | Serum albumin cysteine trioxidation is a potential oxidative stress biomarker of type 2 diabetes mellitus |
title_sort | serum albumin cysteine trioxidation is a potential oxidative stress biomarker of type 2 diabetes mellitus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160123/ https://www.ncbi.nlm.nih.gov/pubmed/32296090 http://dx.doi.org/10.1038/s41598-020-62341-z |
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