Intracellular Pool of Low- and Medium-Molecular-Weight Substances as a Nonspecific Integrative Indicator of Immunometabolism

Authors

DOI:

https://doi.org/10.37482/2687-1491-Z250

Keywords:

lymphocytes, low- and medium-molecular-weight substances, oligopeptides, sirtuin 3, hypoxia-inducible factor 1α, immunometabolism

Abstract

Low- and medium-molecular-weight substances (LMMWS) and oligopeptides (OPs) constitute a pool of heterogeneous molecules formed during metabolic processes. These substances have been found to play a significant role in the development of metabolic shifts in the course of various homeostatic changes. Evidence has been obtained that individual substances in the LMMWS pool participate in the regulation of metabolic pathways. Considering that the metabolic activity of lymphocytes and their capacity for metabolic reprogramming are crucial at all stages of the immune response, determining the intracellular LMMWS pool provides insight into the state of lymphocyte metabolism. The purpose of this research was to study the spectral characteristics of the pool of LMMWS in peripheral blood lymphocytes and to elucidate the nature of the relationship between their quantitative characteristics and intracellular regulators of immunometabolism. Materials and мethods. The lymphocyte fraction of venous blood of people living in the European North of Russia was explored. To evaluate cellular metabolic activity, the content of regulators of glycolysis (HIF-1α) and mitochondrial processes (SIRT3) were determined in the lymphocyte cell lysate using enzyme-linked immunosorbent assay. In lymphocyte supernatants, the optical density of LMMWS in the 224–304 nm wavelength range was measured using a double beam spectrophotometer, after which a spectral curve was plotted and the area under the curve was calculated. OP fraction was measured at a wavelength of 750 nm using the photometric method. Spearman’s rank correlation coefficient was calculated to analyse the relationships. Results. For the first time, the characteristic features of the spectrograms of LMMWS in the supernatants of peripheral blood lymphocytes were recorded and determined. A moderate negative correlation between HIF-1α concentration and the content of LMMWS and OPs in lymphocytes was established. Consistent changes in the immunological reactivity index, HIF-1α/SIRT3 ratio, and LMMWS content were identified. The intracellular content of LMMWS can serve as an informative non-specific criterion, allowing us to promptly assess the metabolic activity of peripheral blood lymphocytes. Changes in this activity are reflected in the spectral curve profile, which facilitates visual monitoring.

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References

Малахова М.Я. Методы биохимической регистрации эндогенной интоксикации (сообщение первое) // Эфферент. терапия. 1995. Т. 1, No 1. С. 61–64.

Малахова М.Я., Зубаткина О.В. Методы верификации донозологических состояний организма // Эфферент. терапия. 2006. Т. 12, No 1. С. 43–50.

Винокуров М.М., Савельев В.В., Хлебный Е.С., Кершенгольц Б.М. Клиническое значение комплексной оценки уровня эндогенной интоксикации у больных в инфекционной фазе панкреонекроза // Дальневост. мед. журн. 2011. No 2. С. 21–24.

Нургалеева Е.А., Еникеев Д.А., Фаршатова Е.Р., Нагаева Л.В., Александров М.А. Роль эндотоксикоза постреанимационного периода, цитокинового профиля, уровня гликозаминогликанов в механизмах повреждения легочной ткани // Астрахан. мед. журн. 2012. Т. 7, No 3. С. 90–94.

Прокофьева Т.В., Полунина О.С., Воронина Л.П., Полунина Е.А., Севостьянова И.В. Прогностическое значение молекул средней массы у больных хронической обструктивной болезнью легких // Acta Biomedica Scientifica. 2022. Т. 7, No 6. С. 34–44. https://doi.org/10.29413/ABS.2022-7.6.4

Cohen G. Immune Dysfunction in Uremia 2020 // Toxins (Basel). 2020. Vol. 12, No 7. Art. No 439. https://doi.org/10.3390/toxins12070439

Wagstaff E.L., Heredero Berzal A., Boon C.J.F., Quinn P.M.J., Ten Asbroek A.L.M.A., Bergen A.A. The Role of Small Molecules and Their Effect on the Molecular Mechanisms of Early Retinal Organoid Development // Int. J. Mol. Sci. 2021. Vol. 22, No 13. Art. No 7081. https://doi.org/10.3390/ijms22137081

Mansouri M., Fussenegger M. Small-Molecule Regulators for Gene Switches to Program Mammalian Cell Behaviour // Chembiochem. 2024. Vol. 25, No 6. Art. No e202300717. https://doi.org/10.1002/cbic.202300717

Matias M.I., Yong C.S., Foroushani A., Goldsmith C., Mongellaz C., Sezgin E., Levental K.R., Talebi A., Perrault J., Rivière A., Dehairs J., Delos O., Bertand-Michel J., Portais J.-C., Wong M., Marie J.C., Kelekar A., Kinet S., Zimmermann V.S., Levental I., Yvan-Charvet L., Swinnen J.V., Muljo S.A., Hernandez-Vargas H., Tardito S., Taylor N., Dardalhon V. Regulatory T Cell Differentiation Is Controlled by αKG-Induced Alterations in Mitochondrial Metabolism and Lipid Homeostasis // Cell Rep. 2021. Vol. 37, No 5. Art. No 109911. https://doi.org/10.1016/j.celrep.2021.109911

Hao F., Tian M., Wang H., Li S., Wang X., Jin X., Wang Y., Jiao Y., Tian M. Exercise-Induced β-Hydroxybutyrate Promotes Treg Cell Differentiation to Ameliorate Colitis in Mice // FASEB J. 2024. Vol. 38, No 4. Art. No e23487. https://doi.org/10.1096/fj.202301686RR

Merry T.L., Chan A., Woodhead J.S.T., Reynolds J.C., Kumagai H., Kim S.-J., Lee C. Mitochondrial-Derived Peptides in Energy Metabolism // Am. J. Physiol. Endocrinol. Metab. 2020. Vol. 319, No 4. Р. E659–E666. https://doi.org/10.1152/ajpendo.00249.2020

de Araujo C.B., Heimann A.S., Remer R.A., Russo L.C., Colquhoun A., Forti F.L., Ferro E.S. Intracellular Peptides in Cell Biology and Pharmacology // Biomolecules. 2019. Vol. 9, No 4. Art. No 150. https://doi.org/10.3390/biom9040150

Lyapina I., Ivanov V., Fesenko I. Peptidome: Chaos or Inevitability // Int. J. Mol. Sci. 2021. Vol. 22, No 23. Art. No 13128. https://doi.org/10.3390/ijms222313128

Khan S., Basu S., Raj D., Lahiri A. Role of Mitochondria in Regulating Immune Response During Bacterial Infection // Int. Rev. Cell Mol. Biol. 2023. Vol. 374. P. 159–200. https://doi.org/10.1016/bs.ircmb.2022.10.004

Ferro E.S., Rioli V., Castro L.M., Fricker L.D. Intracellular Peptides: From Discovery to Function // EuPA Open Proteom. 2014. Vol. 3. P. 143–151. https://doi.org/10.1016/j.euprot.2014.02.009

Rangel Rivera G.O., Knochelmann H.M., Dwyer C.J., Smith A.S., Wyatt M.M., Rivera-Reyes A.M., Thaxton J.E., Paulos C.M. Fundamentals of T Cell Metabolism and Strategies to Enhance Cancer Immunotherapy // Front. Immunol. 2021. Vol. 12. Art. No 645242. https://doi.org/10.3389/fimmu.2021.645242

Chapman N.M., Chi H. Metabolic Adaptation of Lymphocytes in Immunity and Disease // Immunity. 2022. Vol. 55, No 1. Р. 14–30. https://doi.org/10.1016/j.immuni.2021.12.012

Taylor C.T., Scholz C.C. The Effect of HIF on Metabolism and Immunity // Nat. Rev. Nephrol. 2022. Vol. 18, No 9. P. 573–587. https://doi.org/10.1038/s41581-022-00587-8

Zhou L., Pinho R., Gu Y., Radak Z. The Role of SIRT3 in Exercise and Aging // Cells. 2022. Vo l. 11, No 16. Art. No 2596. https://doi.org/10.3390/cells11162596

Гребенникова И.В., Лидохова О.В., Макеева А.В., Бердников А.А., Савченко А.П., Блинова Ю.В., Воронцова З.А. Гематологические индексы при COVID-19: ретроспективное исследование // Вестн. новых мед. технологий. Электрон. изд. 2022. Т. 16, No 6. С. 87–91. https://doi.org/10.24412/2075-4094-2022-6-3-5

Губкина Л.В., Самодова А.В., Добродеева Л.К. Балашова С.Н., Пашинская К.О. Особенности клеточных и гуморальных иммунных реакций у жителей Европейского Севера и Арктики // Якут. мед. журн. 2022. No 4 (80). С. 87–90. https://doi.org/10.25789/YMJ.2022.80.23

Huang X., Zhao L., Peng R. Hypoxia-Inducible Factor 1 and Mitochondria: An Intimate Connection // Biomolecules. 2022. Vol. 13, No 1. Art. No 50. https://doi.org/10.3390/biom13010050

Ma X., Dong Z., Liu J., Ma L., Sun X., Gao R., Pan L., Zhang J., A D., An J., Hu K., Sun A., Ge J. β-Hydroxybutyrate Exacerbates Hypoxic Injury by Inhibiting HIF-1α-Dependent Glycolysis in Cardiomyocytes – Adding Fuel to the Fire // Cardiovasc. Drugs Ther. 2022. Vol. 36, No 3. Р. 383–397. https://doi.org/10.1007/s10557-021-07267-y

Zhang H., Tang K., Ma J., Zhou L., Liu J., Zeng L., Zhu L., Xu P., Chen J., Wei K., Liang X., Lv J., Xie J., Liu Y., Wan Y., Huang B. Ketogenesis-Generated β-Hydroxybutyrate Is an Epigenetic Regulator of CD8+ T-Cell Memory Development // Nat. Cell Biol. 2020. Vol. 22, No 1. Р. 18–25. https://doi.org/10.1038/s41556-019-0440-0

Chen H., Liu J., Chen M., Wei Z., Yuan J., Wu W., Wu Z., Zheng Z., Zhao Z., Lin Q., Liu N. SIRT3 Facilitates Mitochondrial Structural Repair and Functional Recovery in Rats After Ischemic Stroke by Promoting OPA1 Expression and Activity // Clin. Nutr. 2024. Vol. 43, No 7. Р. 1816–1831. https://doi.org/10.1016/j.clnu.2024.06.001

Published

2025-10-17

How to Cite

Zubatkina О. В., & Kruglov С. Д. (2025). Intracellular Pool of Low- and Medium-Molecular-Weight Substances as a Nonspecific Integrative Indicator of Immunometabolism. Journal of Medical and Biological Research, 13(3), 327–338. https://doi.org/10.37482/2687-1491-Z250