Degradation of cardiac troponin I: implication for reliable immunodetection
Abstract
We have analyzed by different immunological methods the proteolytic degradation of cardiac troponin I (cTnI) in human necrotic tissue and in serum. cTnI is susceptible to proteolysis, and its degradation leads to the appearance of a wide diversity of proteolytic peptides with different stabilities. N- and C-terminal regions were rapidly cleaved by proteases, whereas the fragment located between residues 30 and 110 demonstrated substantially higher stability, possibly because of its protection by TnC. We conclude that antibodies selected for cTnI sandwich immunoassays should preferentially recognize epitopes located in the region resistant to proteolysis. Such an approach can be helpful for a much needed standardization of cTnI immunoassays and can improve the sensitivity and reproducibility of cTnI assays.
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The peptide targets the central portion of cTnI (amino acid residues 114-144) with less susceptibility to proteolysis.
“This specific peptide (HWQIAYNEHQWQ) not only exhibits an impressive binding affinity (Kd) of 270 pM comparable to that of antibodies37, but also targets the central portion of cTnI (amino acid residues 114–144) with less susceptibility to proteolysis and is postulated to be an optimal targeting epitope to detect all forms of cTnI present in blood circulation38–40.”
From Nanoproteomics enables proteoform-resolved analysis of low-abundance proteins in human serum (2020) · cites this paper as [38]
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Analytical Characteristics of High-Sensitivity Cardiac Troponin Assays
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Nanoproteomics enables proteoform-resolved analysis of low-abundance proteins in human serum
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- Authors
- Katrukha, A. G., Bereznikova, A. V., Filatov, V. L., Esakova, T. V., Kolosova, O. V., Pettersson, K., Lövgren, T., Bulargina, T. V., Trifonov, I. R., Gratsiansky, N. A., Pulkki, K., Voipio-Pulkki, L.-M., & Gusev, N. B.
- Affiliations
- HyTest (Finland) (FI)
- Lomonosov Moscow State University (RU)
- Department of Biotechnology, Institute of Medical Ecology, Simpheropolskiy bull. 8, 113149 Moscow, Russia
- University of Turku (FI)
- Department of Biotechnology, University of Turku, Tykistokatu 6A, FIN-20520 Turku, Finland
- Moscow City Hospital No 29 (RU)
- Turku University Hospital (FI)
- Turku University Hospital, Central Laboratory, Kiinanmyllynkaty 4–8, FIN-20520 Turku, Finland
- Corresponding author
- Katrukha, Aleksei G
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-12-01
- Volume
- 44
- Issue
- 12
- Pages
- 2433-2440
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- OpenAlex
- W2148344623
- Cited by
- 232
- References
- 20
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 5 · 2015: 8 · 2014: 7 · 2013: 6 · 2012: 12
- FWCI
- 10.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Keywords
- cardiac troponin I, proteolysis, proteolytic peptides, troponin C, epitope stability, sandwich immunoassay, antibody selection, myocardial necrosis, cardiac biomarkers, assay standardization
- MeSH terms
- Amino Acid Sequence, Antibodies, Monoclonal, Epitopes, Humans, Hydrolysis, Molecular Sequence Data, Myocardial Infarction, Myocardium, Peptide Fragments, Endopeptidases, Sensitivity and Specificity, Time Factors, Blotting, Western, Fluoroimmunoassay, Reproducibility of Results, Troponin T
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