Abstract
In this work, we examined by DSC protein denaturation heat capacity profiles for two body fluids, cerebrospinal fluid (CSF) and blood plasma obtained from brain tumor (mainly glioblastoma) patients and healthy volunteers. We observed large distinctions between the heat capacity profiles of CSF and blood plasma, although their protein compositions are believed to have much in common. A prominent, previously unreported CSF feature was the existence of a pre-denaturation exothermic transition peaking at ~ 50–52 °C, recorded for both control and brain tumor CSF. This appears to be the first observation of a pre-denaturation exotherm in a human body fluid. In all studied samples, the exotherms deconvoluted with high precision into a sum of two Gaussian peaks. These exotherms are apparently specific, originating from brain tissue-soluble proteins in the CSF not present in blood plasma. Malignant brain tumors (glioblastoma multiforme, Grade IV, and low-grade glioma, Grade II) reduced twofold the enthalpy of the exotherms relative to the control. These results suggest that the amount and/or conformational state of the CSF proteins (e.g., intrinsic disorder) giving rise to pre-denaturation exothermic events substantially changed upon brain tumor progression. Concomitantly, the enthalpy of the CSF endothermic peaks was partially redistributed from a lower-temperature (main) transition to a higher-temperature transition. The presented data demonstrated that the heat capacity profiles of intrinsic CSF proteins constitute a sensitive biomarker of glioblastoma and other brain malignancies.
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Acknowledgements
We thank Dr. Dimiter Monov for help with the control CSF isolation and the staff of the Central Clinical Laboratory of “St. Ivan Rilski” University Hospital for the protein content determinations. This work was supported by the Bulgarian National Science Research Fund (grant DN03/13/2016).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Research Ethics Committee of Medical University-Sofia (protocol reference No. 24/19.11.2015) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Antonova, B., Naydenov, E., Koynova, R. et al. Exothermic transitions in the heat capacity profiles of human cerebrospinal fluid. Eur Biophys J 49, 231–238 (2020). https://doi.org/10.1007/s00249-020-01429-w
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DOI: https://doi.org/10.1007/s00249-020-01429-w