{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T23:27:45Z","timestamp":1768951665341,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["Ro2327\/13-2"],"award-info":[{"award-number":["Ro2327\/13-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glioblastoma multiforme (GBM) is the most common and malignant brain tumour. It is characterised by transcriptionally distinct cell populations. In tumour cells, physiological pH gradients between the intracellular and extracellular compartments are reversed, compared to non-cancer cells. Intracellular pH in tumour cells is alkaline, whereas extracellular pH is acidic. Consequently, the function and\/or expression of pH regulating transporters might be altered. Here, we investigated protein expression and regulation of the electrogenic sodium\/bicarbonate cotransporter 1 (NBCe1) in mesenchymal (MES)-like hypoxia-dependent and -independent cells, as well as in astrocyte-like glioblastoma cells following chemical hypoxia, acidosis and elucidated putative underlying molecular pathways. Immunoblotting, immunocytochemistry, and intracellular pH recording with the H+-sensitive dye 2\u2032,7\u2032-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein were applied. The results show NBCe1 protein abundance and active NBCe1 transport. Hypoxia upregulated NBCe1 protein and activity in MES-like hypoxia-dependent GBM cells. This effect was positively correlated with HIF-1\u03b1 protein levels, was mediated by TGF-\u03b2 signalling, and was prevented by extracellular acidosis. In MES-like hypoxia-independent GBM cells, acidosis (but not hypoxia) regulated NBCe1 activity in an HIF-1\u03b1-independent manner. These results demonstrate a cell-specific adaptation of NBCe1 expression and activity to the microenvironment challenge of hypoxia and acidosis that depends on their transcriptional signature in GBM.<\/jats:p>","DOI":"10.3390\/ijms23168975","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T21:15:05Z","timestamp":1660252505000},"page":"8975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cell-Type Dependent Regulation of the Electrogenic Na+\/HCO3\u2212 Cotransporter 1 (NBCe1) by Hypoxia and Acidosis in Glioblastoma"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5761-4255","authenticated-orcid":false,"given":"Marina","family":"Giannaki","sequence":"first","affiliation":[{"name":"Department of Molecular Embryology, Faculty of Medicine, Institute of Anatomy and Cell Biology, Albert-Ludwigs-Universit\u00e4t Freiburg, Albertstrasse 17, D-79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debora E.","family":"Ruf","sequence":"additional","affiliation":[{"name":"Department of Molecular Embryology, Faculty of Medicine, Institute of Anatomy and Cell Biology, Albert-Ludwigs-Universit\u00e4t Freiburg, Albertstrasse 17, D-79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilie","family":"Pfeifer","sequence":"additional","affiliation":[{"name":"Department of Molecular Embryology, Faculty of Medicine, Institute of Anatomy and Cell Biology, Albert-Ludwigs-Universit\u00e4t Freiburg, Albertstrasse 17, D-79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Everaerts","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Heinrich Heine University, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9258-3033","authenticated-orcid":false,"given":"Dieter H.","family":"Heiland","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, Medical Center, University of Freiburg, D-79106 Freiburg, Germany"},{"name":"Microenvironment and Immunology Research Laboratory, Medical Center, University of Freiburg, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Schnell","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, Medical Center, University of Freiburg, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9684-3592","authenticated-orcid":false,"given":"Christine R.","family":"Rose","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Heinrich Heine University, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0495-1597","authenticated-orcid":false,"given":"Eleni","family":"Roussa","sequence":"additional","affiliation":[{"name":"Department of Molecular Embryology, Faculty of Medicine, Institute of Anatomy and Cell Biology, Albert-Ludwigs-Universit\u00e4t Freiburg, Albertstrasse 17, D-79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.semcancer.2017.01.007","article-title":"Targeting pH regulating proteins for cancer therapy-progress and limitations","volume":"43","author":"Parks","year":"2017","journal-title":"Semin. 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