Email this article EVALUATION OF METABOLITES PROFILES CHANGES IN SIM-A9 MICROGLIAL CELLS UNDER THE INFLUENCE OF HYPOXIA AND LIPOPOLYSACCHARIDE
- Authors: Bobrov M.1, Nikitin V.1, Burak M.1, Afonin M.1
-
Affiliations:
- Sirius University of Science and Technology (Sirius University)
- Section: Immunological readings in Chelyabinsk
- Submitted: 31.03.2025
- Accepted: 25.05.2025
- URL: https://rusimmun.ru/jour/article/view/17212
- DOI: https://doi.org/10.46235/1028-7221-17212-EOM
- ID: 17212
Cite item
Full Text
Abstract
Abstract
Microglial cells play a leading role in the development of neuroinflammation. Activation of microglia leads to the formation of reactive phenotypes that can both contribute to the development of neuroinflammation and ensure its resolution. Microglia activation is accompanied by metabolic reprogramming or changes in the metabolic pathways activity and the content of specific metabolites supporting a particular phenotype. The possibility of phenotype switching due to metabolomic reprogramming may have undoubted therapeutic potential. However, currently there is limited data on changes in the composition of metabolites and the activity of metabolic pathways in microglial cells under the influence of neuroinflammatory factors. In this regard, the purpose of this work was to conduct a non-targeted metabolomic study to assess changes of metabolites profiles in microglial cell line SIM-A9 exposed to hypoxia, as well as during TLR4 activation.
Metabolite profiling of cell extracts exposed to hypoxia or lipopolysaccharide was performed using high-performance liquid chromatography and high-resolution mass spectrometry, followed by bioinformatics analysis of the data.
The results of the conducted studies indicate that hypoxia, as well as TLR4 stimulation, lead to noticeable changes in the metabolism of microglial cells. At the same time, the nature of these changes depends on the type of stress exposure and its duration. Changes in the activity of glutathione and arginine metabolism pathways can serve as a marker of the polarization of microglial cells after hypoxic exposure. The activation of TLR4 by lipopolysaccharide leads to the modulation of pathways associated with energy metabolism, as well as changes in the metabolic pathways of aromatic amino acids.
It can be concluded that the approach used in this work will allow us to further investigate the dynamics of metabolic changes under the influence of proinflammatory factors of various nature and to detail their role in the metabolic reprogramming of microglial cells at various stages of neuroinflammation.
About the authors
Mikhail Bobrov
Sirius University of Science and Technology (Sirius University)
Email: mbobr@mail.ru
ORCID iD: 0000-0002-5837-473X
SPIN-code: 5909-5612
Scopus Author ID: 7003745294
ResearcherId: С-2993-2014
PhD, Senior Researcher, Department of Immunobiology and Biomedicine, Center for Genetics and Life Sciences, Sirius University
Russian Federation, 354340, Russian Federation, Krasnodar Territory, Federal territory "Sirius", Olympic ave., 1Vadim Nikitin
Sirius University of Science and Technology (Sirius University)
Email: nikitin.vs@talantiuspeh.ru
laboratory research assistant, Immunobiology and Biomedicine, Sirius University
Russian Federation, 354340, Russian Federation, Krasnodar Territory, Federal territory "Sirius", Olympic ave., 1Marina Burak
Sirius University of Science and Technology (Sirius University)
Email: burak.my@talantiuspeh.ru
laboratory research assistant, Immunobiology and Biomedicine, Sirius University
Russian Federation, 354340, Russian Federation, Krasnodar Territory, Federal territory "Sirius", Olympic ave., 1Mikhail Afonin
Sirius University of Science and Technology (Sirius University)
Author for correspondence.
Email: afonin.mb@talantiuspeh.ru
Chief Research Engineer of the Resource Center for Analytical Methods, Sirius University
Russian Federation, 354340, Russian Federation, Krasnodar Territory, Federal territory "Sirius", Olympic ave., 1References
- Chen B., Di B. Endogenous Ligands of TLR4 in Microglia: Potential Targets for Related Neurological Diseases. Curr Drug Targets., 2024, Vol. 25, no. 14, pp. 953-970. doi: 10.2174/0113894501316051240821060249.
- Fan H., Bai Q., Yang Y., Shi X., Du G., Yan J., Shi J., Wang D. The key roles of reactive oxygen species in microglial inflammatory activation: Regulation by endogenous antioxidant system and exogenous sulfur-containing compounds. Eur J Pharmacol., 2023, Vol. 956:175966. doi: 10.1016/j.ejphar.2023.175966.
- Hestad K., Alexander J., Rootwelt H., Aaseth J.O. The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depressive and Neurodegenerative Diseases. Biomolecules., 2022, Vol. 12, no. 7, pp. 998. doi: 10.3390/biom12070998.
- Iskusnykh I.Y., Zakharova A.A., Pathak D. Glutathione in Brain Disorders and Aging. Molecules., 2022, Vol. 27, no. 1, pp 324. doi: 10.3390/molecules27010324.
- Li S., Park Y., Duraisingham S., Strobel F.H., Khan N., Soltow Q.A., Jones D.P., Pulendran B. Predicting Network Activity from High Throughput Metabolomics. PLoS Comput Biol., 2013, Vol 9, no. 7, pp. e1003123. doi: 10.1371/journal.pcbi.1003123
- Liu Y., Wu L., Peng W., Mao X. Glial polarization in neurological diseases: Molecular mechanisms and therapeutic opportunities. Ageing Res Rev., 2025, Vol. 104:102638, pp 1-27. doi: 10.1016/j.arr.2024.102638
- Nair S., Sobotka K.S., Joshi P., Gressens P., Fleiss B., Thornton C., Mallard C., Hagberg H. Lipopolysaccharide‐induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo. Glia., 2019, Vol. 67, no. 6, pp. 1047–1061. doi: 10.1002/glia.23587
- Ock J., Jeong J., Choi W.S., Lee W.H., Kim S.H., Kim I.K., Suk K. Regulation of Toll-like receptor 4 expression and its signaling by hypoxia in cultured microglia. J Neurosci Res., 2007, Vol. 85, pp. 1989–1995. doi: 10.1002/jnr.21322
- Rana A.K., Bhatt B., Gusain C., Biswal S.N., Das D., Kumar M. Neuroimmunometabolism: how metabolism orchestrates immune response in healthy and diseased brain. Am J Physiol Endocrinol Metab., 2025, Vol. 328, no 2, pp. E217-E229. doi: 10.1152/ajpendo.00331.2024.
- Tyrtyshnaia A, Konovalova S, Bondar A, Ermolenko E, Sultanov R, Manzhulo I. Anti-Inflammatory Activity of N-Docosahexaenoylethanolamine and N-Eicosapentaenoylethanolamine in a Mouse Model of Lipopolysaccharide-Induced Neuroinflammation. Int J Mol Sci., 2021, Vol. 22, no. 19, pp. 10728. doi: 10.3390/ijms221910728.
- Wang Y., Leak R.K., Cao G. Microglia-mediated neuroinflammation and neuroplasticity after stroke. Front. Cell. Neurosci., 2022, Vol. 16, pp. 980722. doi: 10.3389/fncel.2022.980722.
- Wang Z., Zhu H., Xiong W. Advances in mass spectrometry-based multi-scale metabolomic methodologies and their applications in biological and clinical investigations. Sci Bull (Beijing)., 2023, Vol. 68, no. 19, pp. 2268-2284. doi: 10.1016/j.scib.2023.08.047.
- Yang S., Qin C., Hu Z.W., Zhou L.Q., Yu H.H., Chen M., Bosco D.B., Wang W., Wu L.J., Tian D.S. Microglia reprogram metabolic profiles for phenotype and function changes in central nervous system. Neurobiol Dis., 2021, Vol. 152:105290. doi: 10.1016/j.nbd.2021.105290.
- Yao L., Kan E.M., Lu J., Hao A., Dheen S.T., Kaur C., Ling E.A. Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia: role of TLR4 in hypoxic microglia. J Neuroinflammation., 2013, Vol. 10, no. 23, pp. 1-21. doi: 10.1186/1742-2094-10-23.
Supplementary files
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).