Hypoxia Induced Downregulation of Na+/H+ Exchanger-1 Activity Decreases Tumor Cell Proliferation
Objectives: Hypoxia and acidosis are the hallmarks of proliferative tumor microenvironment which can modulate the expression and function of Na+/H+ exchanger-1 (NHE1) via hypoxia inducible factor 1 (Hif). Here, we investigate the severity and time dependent effects of chronic hypoxia on NHE1 activit...
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Galenos Publishing House
2025-03-01
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| Series: | Ankara Üniversitesi Tıp Fakültesi Mecmuas |
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| Online Access: | https://www.ankaratipfakultesimecmuasi.net/articles/hypoxia-induced-downregulation-of-nalesssupgreaterlesssupgreaterhlesssupgreaterlesssupgreater-exchanger-1-activity-decreases-tumor-cell-proliferation/doi/atfm.galenos.2025.98624 |
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| author | Gül Şimşek Hilmi Burak Kandilci |
| author_facet | Gül Şimşek Hilmi Burak Kandilci |
| author_sort | Gül Şimşek |
| collection | DOAJ |
| description | Objectives: Hypoxia and acidosis are the hallmarks of proliferative tumor microenvironment which can modulate the expression and function of Na+/H+ exchanger-1 (NHE1) via hypoxia inducible factor 1 (Hif). Here, we investigate the severity and time dependent effects of chronic hypoxia on NHE1 activity and its correlation with cell proliferation in mouse atrium tumor derived HL-1 cells.
Materials and Methods: NHE1 activity was recorded using intracellular pH (pHi) sensitive dye cSNARF-1 (Leica SP5). Cell proliferation was assessed by live cell movie analyzer (Nanoentek, JuLI Br®) or immunofluorescence method.
Results: According to our results, mild chronic hypoxia (2% O2, 48 hours) or shorter duration severe chronic hypoxia (1% O2, 24 hours) did not affect cell proliferation and NHE1 activity. In contrast, long term dimethyloxalylglycine (DMOG, Hif stabilizer) or zoniporide (NHE1 inhibitor) incubations (21% O2, 24/48 hours) suppressed cell proliferation.
Conclusion: When our published and current results in this study interpreted together, at a critical level and duration of chronic hypoxia, Hif mediated downregulation of NHE1 activity could suppress tumor cell proliferation regardless of the well-known anti-proliferative early term direct effects of Hif. Therefore, restriction of NHE1 activity in tumor hypoxia is an important alternative target in regulating anti-proliferative action against tumor cells. |
| format | Article |
| id | doaj-art-3ef93aa0c6244148b6c4ffa44626aafa |
| institution | Kabale University |
| issn | 1307-5608 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Galenos Publishing House |
| record_format | Article |
| series | Ankara Üniversitesi Tıp Fakültesi Mecmuas |
| spelling | doaj-art-3ef93aa0c6244148b6c4ffa44626aafa2025-08-20T03:50:59ZengGalenos Publishing HouseAnkara Üniversitesi Tıp Fakültesi Mecmuas1307-56082025-03-01781495410.4274/atfm.galenos.2025.98624Hypoxia Induced Downregulation of Na+/H+ Exchanger-1 Activity Decreases Tumor Cell ProliferationGül Şimşek0https://orcid.org/0000-0002-3056-6414Hilmi Burak Kandilci1https://orcid.org/0000-0003-3050-6443Ankara University Faculty of Medicine Department of Biophysics, Ankara, TürkiyeAnkara University Faculty of Medicine Department of Biophysics, Ankara, TürkiyeObjectives: Hypoxia and acidosis are the hallmarks of proliferative tumor microenvironment which can modulate the expression and function of Na+/H+ exchanger-1 (NHE1) via hypoxia inducible factor 1 (Hif). Here, we investigate the severity and time dependent effects of chronic hypoxia on NHE1 activity and its correlation with cell proliferation in mouse atrium tumor derived HL-1 cells. Materials and Methods: NHE1 activity was recorded using intracellular pH (pHi) sensitive dye cSNARF-1 (Leica SP5). Cell proliferation was assessed by live cell movie analyzer (Nanoentek, JuLI Br®) or immunofluorescence method. Results: According to our results, mild chronic hypoxia (2% O2, 48 hours) or shorter duration severe chronic hypoxia (1% O2, 24 hours) did not affect cell proliferation and NHE1 activity. In contrast, long term dimethyloxalylglycine (DMOG, Hif stabilizer) or zoniporide (NHE1 inhibitor) incubations (21% O2, 24/48 hours) suppressed cell proliferation. Conclusion: When our published and current results in this study interpreted together, at a critical level and duration of chronic hypoxia, Hif mediated downregulation of NHE1 activity could suppress tumor cell proliferation regardless of the well-known anti-proliferative early term direct effects of Hif. Therefore, restriction of NHE1 activity in tumor hypoxia is an important alternative target in regulating anti-proliferative action against tumor cells.https://www.ankaratipfakultesimecmuasi.net/articles/hypoxia-induced-downregulation-of-nalesssupgreaterlesssupgreaterhlesssupgreaterlesssupgreater-exchanger-1-activity-decreases-tumor-cell-proliferation/doi/atfm.galenos.2025.98624cell culture techniqueshypoxiasodium-hydrogen exchangersneoplasms |
| spellingShingle | Gül Şimşek Hilmi Burak Kandilci Hypoxia Induced Downregulation of Na+/H+ Exchanger-1 Activity Decreases Tumor Cell Proliferation Ankara Üniversitesi Tıp Fakültesi Mecmuas cell culture techniques hypoxia sodium-hydrogen exchangers neoplasms |
| title | Hypoxia Induced Downregulation of Na+/H+ Exchanger-1 Activity Decreases Tumor Cell Proliferation |
| title_full | Hypoxia Induced Downregulation of Na+/H+ Exchanger-1 Activity Decreases Tumor Cell Proliferation |
| title_fullStr | Hypoxia Induced Downregulation of Na+/H+ Exchanger-1 Activity Decreases Tumor Cell Proliferation |
| title_full_unstemmed | Hypoxia Induced Downregulation of Na+/H+ Exchanger-1 Activity Decreases Tumor Cell Proliferation |
| title_short | Hypoxia Induced Downregulation of Na+/H+ Exchanger-1 Activity Decreases Tumor Cell Proliferation |
| title_sort | hypoxia induced downregulation of na h exchanger 1 activity decreases tumor cell proliferation |
| topic | cell culture techniques hypoxia sodium-hydrogen exchangers neoplasms |
| url | https://www.ankaratipfakultesimecmuasi.net/articles/hypoxia-induced-downregulation-of-nalesssupgreaterlesssupgreaterhlesssupgreaterlesssupgreater-exchanger-1-activity-decreases-tumor-cell-proliferation/doi/atfm.galenos.2025.98624 |
| work_keys_str_mv | AT gulsimsek hypoxiainduceddownregulationofnahexchanger1activitydecreasestumorcellproliferation AT hilmiburakkandilci hypoxiainduceddownregulationofnahexchanger1activitydecreasestumorcellproliferation |