Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma Markers
Haptoglobin (Hp) is a blood plasma glycoprotein that plays a critical role in tissue protection and the prevention of oxidative damage. Haptoglobin is an acute-phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Hap...
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2021-06-01
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author | Stanislav Naryzhny Natalia Ronzhina Elena Zorina Fedor Kabachenko Maria Zavialova Viktor Zgoda Nikolai Klopov Olga Legina Rimma Pantina |
author_facet | Stanislav Naryzhny Natalia Ronzhina Elena Zorina Fedor Kabachenko Maria Zavialova Viktor Zgoda Nikolai Klopov Olga Legina Rimma Pantina |
author_sort | Stanislav Naryzhny |
collection | DOAJ |
description | Haptoglobin (Hp) is a blood plasma glycoprotein that plays a critical role in tissue protection and the prevention of oxidative damage. Haptoglobin is an acute-phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Haptoglobin is a conservative protein and is the subject of research as a potential biomarker of many diseases, including malignant neoplasms. The Human <i>Hp</i> gene is polymorphic and controls the synthesis of three major phenotypes—homozygous Hp1-1 and Hp2-2, and heterozygous Hp2-1, determined by a combination of allelic variants that are inherited. Numerous studies indicate that the phenotype of haptoglobin can be used to judge the individual’s predisposition to various diseases. In addition, Hp undergoes various post-translational modifications (PTMs). Glioblastoma multiform (GBM) is the most malignant primary brain tumor. In our study, we have analyzed the state of Hp proteoforms in plasma and cells using 1D (SDS-PAGE) and 2D electrophoresis (2DE) with the following mass spectrometry (LC ES-MS/MS) or Western blotting. We found that the levels of α2- and β-chain proteoforms are up-regulated in the plasma of GBM patients. An unprocessed form of Hp2-2 (PreHp2-2, zonulin) with unusual biophysical parameters (pI/<i>M</i>w) was also detected in the plasma of GBM patients and glioblastoma cells. Altogether, this data shows the possibility to use proteoforms of haptoglobin as a potential GBM-specific plasma biomarker. |
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spelling | doaj.art-ed3d68d829e24c8b98b68e8e164004072023-11-22T00:39:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012212653310.3390/ijms22126533Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma MarkersStanislav Naryzhny0Natalia Ronzhina1Elena Zorina2Fedor Kabachenko3Maria Zavialova4Viktor Zgoda5Nikolai Klopov6Olga Legina7Rimma Pantina8Institute of Biomedical Chemistry, Pogodinskaya, 10, 119121 Moscow, RussiaNational Research Center “Kurchatov Institute”, Petersburg Nuclear Physics Institute, 188300 Gatchina, RussiaInstitute of Biomedical Chemistry, Pogodinskaya, 10, 119121 Moscow, RussiaPeter the Great St. Petersburg Polytechnic University, 195251 St. Petersburg, RussiaInstitute of Biomedical Chemistry, Pogodinskaya, 10, 119121 Moscow, RussiaInstitute of Biomedical Chemistry, Pogodinskaya, 10, 119121 Moscow, RussiaNational Research Center “Kurchatov Institute”, Petersburg Nuclear Physics Institute, 188300 Gatchina, RussiaNational Research Center “Kurchatov Institute”, Petersburg Nuclear Physics Institute, 188300 Gatchina, RussiaNational Research Center “Kurchatov Institute”, Petersburg Nuclear Physics Institute, 188300 Gatchina, RussiaHaptoglobin (Hp) is a blood plasma glycoprotein that plays a critical role in tissue protection and the prevention of oxidative damage. Haptoglobin is an acute-phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Haptoglobin is a conservative protein and is the subject of research as a potential biomarker of many diseases, including malignant neoplasms. The Human <i>Hp</i> gene is polymorphic and controls the synthesis of three major phenotypes—homozygous Hp1-1 and Hp2-2, and heterozygous Hp2-1, determined by a combination of allelic variants that are inherited. Numerous studies indicate that the phenotype of haptoglobin can be used to judge the individual’s predisposition to various diseases. In addition, Hp undergoes various post-translational modifications (PTMs). Glioblastoma multiform (GBM) is the most malignant primary brain tumor. In our study, we have analyzed the state of Hp proteoforms in plasma and cells using 1D (SDS-PAGE) and 2D electrophoresis (2DE) with the following mass spectrometry (LC ES-MS/MS) or Western blotting. We found that the levels of α2- and β-chain proteoforms are up-regulated in the plasma of GBM patients. An unprocessed form of Hp2-2 (PreHp2-2, zonulin) with unusual biophysical parameters (pI/<i>M</i>w) was also detected in the plasma of GBM patients and glioblastoma cells. Altogether, this data shows the possibility to use proteoforms of haptoglobin as a potential GBM-specific plasma biomarker.https://www.mdpi.com/1422-0067/22/12/6533haptoglobinbiomarkerzonulinglioblastoma |
spellingShingle | Stanislav Naryzhny Natalia Ronzhina Elena Zorina Fedor Kabachenko Maria Zavialova Viktor Zgoda Nikolai Klopov Olga Legina Rimma Pantina Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma Markers International Journal of Molecular Sciences haptoglobin biomarker zonulin glioblastoma |
title | Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma Markers |
title_full | Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma Markers |
title_fullStr | Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma Markers |
title_full_unstemmed | Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma Markers |
title_short | Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma Markers |
title_sort | evaluation of haptoglobin and its proteoforms as glioblastoma markers |
topic | haptoglobin biomarker zonulin glioblastoma |
url | https://www.mdpi.com/1422-0067/22/12/6533 |
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