Variability of haptoglobin beta-chain proteoforms

Ronzhina N.L.1, Zorina E.S.2, Zavialova M.G.2, Legina O.K.1, Naryzhny S.N.1

1. B.P. Konstantinov Petersburg Institute of Nuclear Physics, National Research Center “Kurchatov Institute”, Gatchina, Leningrad Region, Russia
2. Institute of Biomedical Chemistry, Moscow, Russia
Section: Clinical and Diagnostic Research
DOI: 10.18097/PBMC20247002114      PubMed Id: 38711411
Year: 2024  Volume: 70  Issue: 2  Pages: 114-124
Existing knowledge on changes of the haptoglobin (Hp) molecule suggests that it may exist in multiple proteoforms, which obviously exhibit different functions. Using two-dimensional electrophoresis (2DE) in combination with mass spectrometry and immunodetection, we have analyzed blood plasma samples from both healthy donors and patients with primary grade IV glioblastoma (GBM), and obtained a detailed composite 2DE distribution map of β-chain proteoforms, as well as the full-length form of Hp (zonulin). Although the total level of plasma Hp exceeded normal values in cancer patients (especially patients with GBM), the presence of particuar proteoforms, detected by their position on the 2DE map, was very individual. Variability was found in both zonulin and the Hp β-chain. The presence of an alkaline form of zonulin in plasma can be considered a conditional, but insufficient, GBM biomarker. In other words, we found that at the level of minor proteoforms of Hp, even in normal conditions, there was a high individual variability. On the one hand, this raises questions about the reasons for such variability, if it is present not only in Hp, but also in other proteins. On the other hand, this may explain the discrepancy between the number of experimentally detected proteoforms and the theoretically possible ones not only in Hp, but also in other proteins.
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Keywords: haptoglobin, proteoforms, glioblastoma, individual variability

Ronzhina, N. L., Zorina, E. S., Zavialova, M. G., Legina, O. K., Naryzhny, S. N. (2024). Variability of haptoglobin beta-chain proteoforms. Biomeditsinskaya Khimiya, 70(2), 114-124.
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