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Cited by 41Redox biology and oxidative stressAntioxidant Activity and Oxidative StressAdvanced Proteomics Techniques and Applications

Serum albumin cysteine trioxidation is a potential oxidative stress biomarker of type 2 diabetes mellitus

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Paramasivan, Selvam, Adav, Sunil S., Ngan, SoFong Cam, Dalan, Rinkoo, Leow, Melvin Khee-Shing, Ho, Hee Hwa, Sze, Siu Kwan·2020·Scientific Reports
DOI 10.1038/s41598-020-62341-zPMC PMC7160123
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Abstract

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.

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  • Trioxidized peptides have potential as prognostic biomarkers of protein oxidation in human disease.

    “By using a LC-MS/MS approach, they found elevated cysteine sulfonic acid in human serum albumin of type 2 diabetes (T2D) patients compared to control subjects, indicating the potential of trioxidized peptides as prognostic biomarker of protein oxidation in human disease [125].”

    From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [125]

    The Introduction says site-specific trioxidized human serum albumin could be a biomarker of diabetes diagnosis and prognosis. The Conclusion limits the proposed prognostic use to diabetes and says its relationship to disease severity and outcomes still needs a larger longitudinal study. The claim extends that potential to human disease generally. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Cysteine sulfonic acid is elevated in human serum albumin of type 2 diabetes patients compared to control subjects.

    “By using a LC-MS/MS approach, they found elevated cysteine sulfonic acid in human serum albumin of type 2 diabetes (T2D) patients compared to control subjects, indicating the potential of trioxidized peptides as prognostic biomarker of protein oxidation in human disease [125].”

    From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [125]

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Research works printed but not linked: 37

  1. [1]Lin Y Sun Z Current views on type 2 diabetes The Journal of endocrinology 2010 204 1 10.1677/JOE-09-0260 19770178 PMC2814170 · DOI · Paper page
  2. [2]Wiernsperger N Oxidative stress as a therapeutic target in diabetes: revisiting the controversy Diabetes & metabolism 2003 29 579 585 10.1016/S1262-3636(07)70072-1 14707886 · DOI
  3. [3]Dominguez C Ruiz E Gussinye M Carrascosa A Oxidative stress at onset and in early stages of type 1 diabetes in children and adolescents Diabetes care 1998 21 1736 1742 10.2337/diacare.21.10.1736 9773740 · DOI
  4. [5]Selvin E Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus Annals of internal medicine 2004 141 421 431 10.7326/0003-4819-141-6-200409210-00007 15381515 · DOI · Paper page
  5. [6]The International Expert Committee International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes Diabetes care 2009 32 1327 1334 10.2337/dc09-9033 19502545 PMC2699715 · DOI · Paper page
  6. [7]WHO. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus: abbreviated report of a WHO consultation, http://www.who.int/diabetes/publications/report-hba1c_2011.pdf. (2011). 26158184
  7. [8]Kirwan A Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics BioMed Research International 2015 2015 16 10.1155/2015/490531 PMC4609776 26509158 · DOI
  8. [9]Adav SS Dementia-linked amyloidosis is associated with brain protein deamidation as revealed by proteomic profiling of human brain tissues Molecular brain 2016 9 20 10.1186/s13041-016-0200-z 26892330 PMC4759965 · DOI
  9. [10]Adav SS iTRAQ quantitative clinical proteomics revealed role of Na(+)K(+)-ATPase and its correlation with deamidation in vascular dementia Journal of proteome research 2014 13 4635 4646 10.1021/pr500754j 25152327 · DOI
  10. [11]Adav SS Sze SK Insight of brain degenerative protein modifications in the pathology of neurodegeneration and dementia by proteomic profiling Molecular brain 2016 9 92 10.1186/s13041-016-0272-9 27809929 PMC5094070 · DOI
  11. [12]Hao P Adav SS Gallart-Palau X Sze SK Recent advances in mass spectrometric analysis of protein deamidation Mass spectrometry reviews 2017 36 677 692 10.1002/mas.21491 26763661 · DOI
  12. [13]Gallart-Palau X Gender differences in white matter pathology and mitochondrial dysfunction in Alzheimer’s disease with cerebrovascular disease Molecular brain 2016 9 27 10.1186/s13041-016-0205-7 26983404 PMC4794845 · DOI
  13. [14]Gallart-Palau X Serra A Lee BST Guo X Sze SK Brain ureido degenerative protein modifications are associated with neuroinflammation and proteinopathy in Alzheimer’s disease with cerebrovascular disease Journal of neuroinflammation 2017 14 175 10.1186/s12974-017-0946-y 28865468 PMC5581431 · DOI
  14. [15]Jeong J Novel Oxidative Modifications in Redox-Active Cysteine Residues Molecular & Cellular Proteomics: MCP 2011 10 M110.000513 10.1074/mcp.M110.000513 21148632 PMC3047142 · DOI
  15. [16]Anavi S Madar Z Tirosh O Non-alcoholic fatty liver disease, to struggle with the strangle: Oxygen availability in fatty livers. Redox Biology 2017 13 386 392 10.1016/j.redox.2017.06.008 PMC5493836 28667907 · DOI
  16. [18]Soejima A Useful markers for detecting decreased serum antioxidant activity in hemodialysis patients American journal of kidney diseases: the official journal of the National Kidney Foundation 2002 39 1040 1046 10.1053/ajkd.2002.32787 11979348 · DOI
  17. [19]Hayakawa A Alteration of redox state of human serum albumin in patients under anesthesia and invasive surgery Journal of chromatography. B, Biomedical sciences and applications 1997 698 27 33 10.1016/S0378-4347(97)00274-0 9367190 · DOI
  18. [20]Paulech J Liddy KA Engholm-Keller K White MY Cordwell SJ Global analysis of myocardial peptides containing cysteines with irreversible sulfinic and sulfonic acid post-translational modifications Mol Cell Proteomics 2015 14 609 620 10.1074/mcp.M114.044347 25561502 PMC4349981 · DOI
  19. [21]Li R Quantitative Protein Sulfenic Acid Analysis Identifies Platelet Releasate-Induced Activation of Integrin beta2 on Monocytes via NADPH Oxidase Journal of proteome research 2016 15 4221 4233 10.1021/acs.jproteome.6b00212 27690452 · DOI
  20. [22]Jensen TM Association between protein signals and type 2 diabetes incidence Acta diabetologica 2013 50 697 704 10.1007/s00592-012-0376-3 22310914 PMC4181558 · DOI
  21. [23]Zhi W Discovery and validation of serum protein changes in type 1 diabetes patients using high throughput two dimensional liquid chromatography-mass spectrometry and immunoassays Molecular & Cellular Proteomics 2011 10 M111. 012203 10.1074/mcp.M111.012203 PMC3226412 21900154 · DOI
  22. [24]Sundsten T Zethelius B Berne C Bergsten P Plasma proteome changes in subjects with Type 2 diabetes mellitus with a low or high early insulin response Clinical science 2008 114 499 507 10.1042/CS20070323 17961122 · DOI
  23. [25]Bae JC Association between Serum Albumin, Insulin Resistance, and Incident Diabetes in Nondiabetic Subjects Endocrinology and metabolism (Seoul, Korea) 2013 28 26 32 10.3803/EnM.2013.28.1.26 PMC3811792 24396647 · DOI
  24. [26]MacLean B Skyline: an open source document editor for creating and analyzing targeted proteomics experiments Bioinformatics 2010 26 966 968 10.1093/bioinformatics/btq054 20147306 PMC2844992 · DOI · Paper page
  25. [27]Liebler DC Protein damage by reactive electrophiles: targets and consequences Chemical research in toxicology 2008 21 117 128 10.1021/tx700235t 18052106 PMC2533766 · DOI
  26. [28]Li H Profiling Cys34 adducts of human serum albumin by fixed-step selected reaction monitoring Mol Cell Proteomics 2011 10 M110.004606 10.1074/mcp.M110.004606 21193536 PMC3047157 · DOI
  27. [29]Bar-Or R Rael LT Bar-Or D Dehydroalanine derived from cysteine is a common post-translational modification in human serum albumin Rapid communications in mass spectrometry: RCM 2008 22 711 716 10.1002/rcm.3421 18265430 · DOI
  28. [30]Evans JL Goldfine ID Maddux BA Grodsky GM Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 2003 52 1 8 10.2337/diabetes.52.1.1 12502486 · DOI · Paper page
  29. [31]Styskal J Van Remmen H Richardson A Salmon AB Oxidative stress and diabetes: what can we learn about insulin resistance from antioxidant mutant mouse models? Free radical biology & medicine 2012 52 46 58 10.1016/j.freeradbiomed.2011.10.441 22056908 PMC3249484 · DOI
  30. [32]Carter DC Ho JX Structure of serum albumin Advances in protein chemistry 1994 45 153 203 10.1016/S0065-3233(08)60640-3 8154369 · DOI
  31. [33]Roche M Rondeau P Singh NR Tarnus E Bourdon E The antioxidant properties of serum albumin FEBS letters 2008 582 1783 1787 10.1016/j.febslet.2008.04.057 18474236 · DOI · Paper page
  32. [34]Jalan R Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality Hepatology (Baltimore, Md.) 2009 50 555 564 10.1002/hep.22913 19642174 · DOI
  33. [35]Oettl K Oxidative albumin damage in chronic liver failure: relation to albumin binding capacity, liver dysfunction and survival Journal of hepatology 2013 59 978 983 10.1016/j.jhep.2013.06.013 23811308 · DOI
  34. [36]Faure P Albumin antioxidant capacity is modified by methylglyoxal Diabetes Metab 2005 31 169 177 10.1016/S1262-3636(07)70183-0 15959423 · DOI
  35. [37]Faure P Wiernsperger N Polge C Favier A Halimi S Impairment of the antioxidant properties of serum albumin in patients with diabetes: protective effects of metformin Clinical science (London, England: 1979) 2008 114 251 256 10.1042/cs20070276 17922677 · DOI
  36. [38]Serra A Plasma proteome coverage is increased by unique peptide recovery from sodium deoxycholate precipitate Analytical and bioanalytical chemistry 2016 408 1963 1973 10.1007/s00216-016-9312-7 26804737 · DOI
  37. [39]Hao P Novel application of electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) in shotgun proteomics: comprehensive profiling of rat kidney proteome Journal of proteome research 2010 9 3520 3526 10.1021/pr100037h 20450224 · DOI

Cited by

Sorted by citations

Authors
Paramasivan, S., Adav, S. S., Ngan, S. C., Dalan, R., Leow, M. K.-S., Ho, H. H., & Sze, S. K.
Affiliations
  • Nanyang Technological University (SG)
  • Tan Tock Seng Hospital (SG)
  • National University of Singapore (SG)
Corresponding author
Sze, Siu Kwan
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2020-04-15
Volume
10
Issue
1
Pages
6475-6475
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-020-62341-z
PMC
PMC7160123
OpenAlex
W3017096941
Cited by
41
References
2
Citations by year
2026: 3 · 2025: 6 · 2024: 6 · 2023: 9 · 2022: 2 · 2021: 13 · 2020: 1 · 2015: 1
FWCI
2.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion)
  • DR-NTU (Nanyang Technological University) (submittedVersion, cc-by)
Funders
  • National Medical Research Council of Singapore (NMRC-OF-IRG-0003-2016)
  • Singapore Ministry of Education (MOE2016-T2-2-018)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
type 2 diabetes, oxidative stress, human serum albumin, thiol oxidation, oxidative stress biomarkers, plasma proteomics, early detection of diabetes
MeSH terms
Serum Albumin, Human, Aged, Chromatography, High Pressure Liquid, Cysteine, Diabetes Mellitus, Type 2, Female, Humans, Male, Middle Aged, Oxidation-Reduction, Prognosis, Biomarkers, Case-Control Studies, Oxidative Stress, Disease Progression, Proteomics, Early Diagnosis, Tandem Mass Spectrometry

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