TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines
IntroductionT-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 TI...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-11-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1267578/full |
| _version_ | 1827763698472583168 |
|---|---|
| author | Mahnaz Rezaei Mustafa Ghanadian Behrooz Ghezelbash Abolfazl Shokouhi Alexandr V. Bazhin Andrey A. Zamyatnin Andrey A. Zamyatnin Andrey A. Zamyatnin Andrey A. Zamyatnin Mazdak Ganjalikhani-Hakemi Mazdak Ganjalikhani-Hakemi |
| author_facet | Mahnaz Rezaei Mustafa Ghanadian Behrooz Ghezelbash Abolfazl Shokouhi Alexandr V. Bazhin Andrey A. Zamyatnin Andrey A. Zamyatnin Andrey A. Zamyatnin Andrey A. Zamyatnin Mazdak Ganjalikhani-Hakemi Mazdak Ganjalikhani-Hakemi |
| author_sort | Mahnaz Rezaei |
| collection | DOAJ |
| description | IntroductionT-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.MethodsHL-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.ResultsWe 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).ConclusionTIM-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. |
| first_indexed | 2024-03-11T10:54:44Z |
| format | Article |
| id | doaj.art-e4b781bf68234e0bbc8635549295e17b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T10:54:44Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e4b781bf68234e0bbc8635549295e17b2023-11-13T11:26:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-11-011410.3389/fimmu.2023.12675781267578TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell linesMahnaz Rezaei0Mustafa Ghanadian1Behrooz Ghezelbash2Abolfazl Shokouhi3Alexandr V. Bazhin4Andrey A. Zamyatnin5Andrey A. Zamyatnin6Andrey A. Zamyatnin7Andrey A. Zamyatnin8Mazdak Ganjalikhani-Hakemi9Mazdak Ganjalikhani-Hakemi10Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, IranDepartment of Pharmacognosy, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, IranDepartment of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, IranEndocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, IranDepartment of General, Visceral and Transplant Surgery, Ludwig Maximilians University of Munich, Munich, GermanyFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, RussiaScientific Center for Translation Medicine, Sirius University of Science and Technology, Sochi, RussiaInstitute of Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, RussiaDepartment of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, IranRegenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, TürkiyeIntroductionT-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.MethodsHL-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.ResultsWe 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).ConclusionTIM-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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1267578/fullacute myeloid leukemiaTIM-3immunometabolismglucose metabolismlipid metabolismgalectin-9 |
| spellingShingle | Mahnaz Rezaei Mustafa Ghanadian Behrooz Ghezelbash Abolfazl Shokouhi Alexandr V. Bazhin Andrey A. Zamyatnin Andrey A. Zamyatnin Andrey A. Zamyatnin Andrey A. Zamyatnin Mazdak Ganjalikhani-Hakemi Mazdak Ganjalikhani-Hakemi TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines Frontiers in Immunology acute myeloid leukemia TIM-3 immunometabolism glucose metabolism lipid metabolism galectin-9 |
| title | TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines |
| title_full | TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines |
| title_fullStr | TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines |
| title_full_unstemmed | TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines |
| title_short | TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines |
| title_sort | tim 3 gal 9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines |
| topic | acute myeloid leukemia TIM-3 immunometabolism glucose metabolism lipid metabolism galectin-9 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1267578/full |
| work_keys_str_mv | AT mahnazrezaei tim3gal9interactionaffectsglucoseandlipidmetabolisminacutemyeloidleukemiacelllines AT mustafaghanadian tim3gal9interactionaffectsglucoseandlipidmetabolisminacutemyeloidleukemiacelllines AT behroozghezelbash tim3gal9interactionaffectsglucoseandlipidmetabolisminacutemyeloidleukemiacelllines AT abolfazlshokouhi tim3gal9interactionaffectsglucoseandlipidmetabolisminacutemyeloidleukemiacelllines AT alexandrvbazhin tim3gal9interactionaffectsglucoseandlipidmetabolisminacutemyeloidleukemiacelllines AT andreyazamyatnin tim3gal9interactionaffectsglucoseandlipidmetabolisminacutemyeloidleukemiacelllines AT andreyazamyatnin tim3gal9interactionaffectsglucoseandlipidmetabolisminacutemyeloidleukemiacelllines AT andreyazamyatnin tim3gal9interactionaffectsglucoseandlipidmetabolisminacutemyeloidleukemiacelllines AT andreyazamyatnin tim3gal9interactionaffectsglucoseandlipidmetabolisminacutemyeloidleukemiacelllines AT mazdakganjalikhanihakemi tim3gal9interactionaffectsglucoseandlipidmetabolisminacutemyeloidleukemiacelllines AT mazdakganjalikhanihakemi tim3gal9interactionaffectsglucoseandlipidmetabolisminacutemyeloidleukemiacelllines |