AMPK Activation in TET2 Downregulated Leukemia Cells Upon Glutamine Limitation
Objective: Metabolic rewiring is a characteristic of cancer cells. Cancer cells require more nutrients for survival and proliferation. Although glutamine can be produced in cells via a series of enzymatic reactions, a group of cancer cells are dependent on extracellular glutamine for survival. TET2...
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Galenos Publishing House
2024-09-01
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| Series: | Medeniyet Medical Journal |
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| Online Access: | https://jag.journalagent.com/z4/download_fulltext.asp?pdir=medeniyet&un=MEDJ-59683 |
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| author | Ahsen Merve BAYRAK Burcu YUCEL |
| author_facet | Ahsen Merve BAYRAK Burcu YUCEL |
| author_sort | Ahsen Merve BAYRAK |
| collection | DOAJ |
| description | Objective: Metabolic rewiring is a characteristic of cancer cells. Cancer cells require more nutrients for survival and proliferation. Although glutamine can be produced in cells via a series of enzymatic reactions, a group of cancer cells are dependent on extracellular glutamine for survival. TET2 plays a role in DNA demethylation and is a tumor suppressor gene. The TET2 gene is frequently mutated in various cancers, including acute myeloid leukemia (AML). Our study aimed to investigate the association between TET2-knockdown AML cell line HL-60 cells and glutamine metabolism.
Methods: To evaluate the association between TET2 expression and glutamine limitation, TET2 was downregulated in HL 60 cells using shRNA plasmids. The proliferation of TET2-knockdown HL-60 cells was calculated in normal and glutamine deficient medium. GLUL mRNA expression was investigated using quantitative reverse transcription polymerase chain reaction and protein levels were evaluated using immunoblotting.
Results: The numbers and viability of TET2-knockdown HL-60 cells were decreased in low glutamine-containing medium, but the viability of TET2-knockdown HL-60 cells was higher than that of control cells. GLUL mRNA expressions were increased in TET2- knockdown cells in low glutamine. In addition, P-AMPKα protein expression was increased in TET2-knockdown HL-60 cells in low glutamine-containing medium.
Conclusions: Our findings indicate that TET2-knockdown HL-60 cells may be more resistant to glutamine deprivation. In glutamine-deficient medium, the mRNA expression of glutamine synthetase is increased, which could be related to glutamine addiction in cells. In addition, low-glutamyl medium increased the P-AMPKα protein level in TET2-knockdown HL-60 cells. |
| format | Article |
| id | doaj-art-bbcb1c8af762433a84794b15e08702f5 |
| institution | Kabale University |
| issn | 2149-2042 2149-4606 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Galenos Publishing House |
| record_format | Article |
| series | Medeniyet Medical Journal |
| spelling | doaj-art-bbcb1c8af762433a84794b15e08702f52025-01-29T10:22:46ZengGalenos Publishing HouseMedeniyet Medical Journal2149-20422149-46062024-09-0139316116810.4274/MMJ.galenos.2024.59683MEDJ-59683AMPK Activation in TET2 Downregulated Leukemia Cells Upon Glutamine LimitationAhsen Merve BAYRAK0Burcu YUCEL1Istanbul Medeniyet University Institute of Graduate Studies, Department of Molecular Medicine, Istanbul, Türkiye and Istanbul Medeniyet University Faculty of Medicine, Department of Medical Biology, Istanbul, TürkiyeIstanbul Medeniyet University Faculty of Medicine, Department of Medical Biology, Istanbul, Türkiye, Istanbul Medeniyet University, Science and Advanced Technologies Research Center (BILTAM), Istanbul, Türkiye and Health Institutes of Türkiye (TUSEB), Türkiye Cancer Institute, Istanbul, TürkiyeObjective: Metabolic rewiring is a characteristic of cancer cells. Cancer cells require more nutrients for survival and proliferation. Although glutamine can be produced in cells via a series of enzymatic reactions, a group of cancer cells are dependent on extracellular glutamine for survival. TET2 plays a role in DNA demethylation and is a tumor suppressor gene. The TET2 gene is frequently mutated in various cancers, including acute myeloid leukemia (AML). Our study aimed to investigate the association between TET2-knockdown AML cell line HL-60 cells and glutamine metabolism. Methods: To evaluate the association between TET2 expression and glutamine limitation, TET2 was downregulated in HL 60 cells using shRNA plasmids. The proliferation of TET2-knockdown HL-60 cells was calculated in normal and glutamine deficient medium. GLUL mRNA expression was investigated using quantitative reverse transcription polymerase chain reaction and protein levels were evaluated using immunoblotting. Results: The numbers and viability of TET2-knockdown HL-60 cells were decreased in low glutamine-containing medium, but the viability of TET2-knockdown HL-60 cells was higher than that of control cells. GLUL mRNA expressions were increased in TET2- knockdown cells in low glutamine. In addition, P-AMPKα protein expression was increased in TET2-knockdown HL-60 cells in low glutamine-containing medium. Conclusions: Our findings indicate that TET2-knockdown HL-60 cells may be more resistant to glutamine deprivation. In glutamine-deficient medium, the mRNA expression of glutamine synthetase is increased, which could be related to glutamine addiction in cells. In addition, low-glutamyl medium increased the P-AMPKα protein level in TET2-knockdown HL-60 cells.https://jag.journalagent.com/z4/download_fulltext.asp?pdir=medeniyet&un=MEDJ-59683glutamine metabolismtet2 expressionamlampkshrnamediated gene silencing |
| spellingShingle | Ahsen Merve BAYRAK Burcu YUCEL AMPK Activation in TET2 Downregulated Leukemia Cells Upon Glutamine Limitation Medeniyet Medical Journal glutamine metabolism tet2 expression aml ampk shrnamediated gene silencing |
| title | AMPK Activation in TET2 Downregulated Leukemia Cells Upon Glutamine Limitation |
| title_full | AMPK Activation in TET2 Downregulated Leukemia Cells Upon Glutamine Limitation |
| title_fullStr | AMPK Activation in TET2 Downregulated Leukemia Cells Upon Glutamine Limitation |
| title_full_unstemmed | AMPK Activation in TET2 Downregulated Leukemia Cells Upon Glutamine Limitation |
| title_short | AMPK Activation in TET2 Downregulated Leukemia Cells Upon Glutamine Limitation |
| title_sort | ampk activation in tet2 downregulated leukemia cells upon glutamine limitation |
| topic | glutamine metabolism tet2 expression aml ampk shrnamediated gene silencing |
| url | https://jag.journalagent.com/z4/download_fulltext.asp?pdir=medeniyet&un=MEDJ-59683 |
| work_keys_str_mv | AT ahsenmervebayrak ampkactivationintet2downregulatedleukemiacellsuponglutaminelimitation AT burcuyucel ampkactivationintet2downregulatedleukemiacellsuponglutaminelimitation |