TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines

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dc.contributor.authorRezaei, Mahnaz
dc.contributor.authorGhanadian, Mustafa
dc.contributor.authorGhezelbash, Behrooz
dc.contributor.authorShokouhi, Abolfazl
dc.contributor.authorBazhin, Alexandr V.
dc.contributor.authorZamyatnin, Andrey A.
dc.contributor.authorGanjalikhani-Hakemi, Mazdak
dc.date.accessioned2023-12-13T12:07:39Z
dc.date.available2023-12-13T12:07:39Z
dc.date.issued2023
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsü
dc.description.abstractIntroduction: T-cell immunoglobulin and mucin domain-3 (TIM-3) is a transmembrane molecule first identified as an immunoregulator. This molecule is also expressed on leukemic cells in acute myeloid leukemia and master cell survival and proliferation. In this study, we aimed to explore the effect of TIM-3 interaction with its ligand galectin-9 (Gal-9) on glucose and lipid metabolism in AML cell lines. Methods: HL-60 and THP-1 cell lines, representing M3 and M5 AML subtypes, respectively, were cultured under appropriate conditions. The expression of TIM-3 on the cell surface was ascertained by flow cytometric assay. We used real-time PCR to examine the mRNA expression of GLUT-1, HK-2, PFKFB-3, G6PD, ACC-1, ATGL, and CPT-1A; colorimetric assays to measure the concentration of glucose, lactate, GSH, and the enzymatic activity of G6PD; MTT assay to determine cellular proliferation; and gas chromatography–mass spectrometry (GC-MS) to designate FFAs. Results: We observed the significant upregulated expression of GLUT-1, HK-2, PFKFB-3, ACC-1, CPT-1A, and G6PD and the enzymatic activity of G6PD in a time-dependent manner in the presence of Gal-9 compared to the PMA and control groups in both HL-60 and THP-1 cell lines (p > 0.05). Moreover, the elevation of extracellular free fatty acids, glucose consumption, lactate release, the concentration of cellular glutathione (GSH) and cell proliferation were significantly higher in the presence of Gal-9 compared to the PMA and control groups in both cell lines (p < 0.05). Conclusion: TIM-3/Gal-9 ligation on AML cell lines results in aerobic glycolysis and altered lipid metabolism and also protects cells from oxidative stress, all in favor of leukemic cell survival and proliferation.
dc.description.sponsorshipIsfahan University of Medical Sciencesen_US
dc.identifier.citationRezaei, M., Ghanadian, M., Ghezelbash, B., Shokouhi, A., Bazhin, A. V., Zamyatnin, A. A. ... Ganjalikhani-Hakemi, M. (2023). TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines. Frontiers in Immunology, 14. https://dx.doi.org/10.3389/fimmu.2023.1267578
dc.identifier.doi10.3389/fimmu.2023.1267578
dc.identifier.issn1664-3224
dc.identifier.pmid38022614
dc.identifier.scopus2-s2.0-85177637670
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://dx.doi.org/10.3389/fimmu.2023.1267578
dc.identifier.urihttps://hdl.handle.net/20.500.12511/11990
dc.identifier.volume14
dc.identifier.wos001108922300001en_US
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorGanjalikhani-Hakemi, Mazdak
dc.language.isoen
dc.publisherFrontiers Media SA
dc.relation.ispartofFrontiers in Immunologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsAttribution 4.0 International*
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectAcute Myeloid Leukemia
dc.subjectGalectin-9
dc.subjectGlucose Metabolism
dc.subjectImmunometabolism
dc.subjectLipid Metabolism
dc.subjectTIM-3
dc.titleTIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines
dc.typeArticle

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