{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:49:42Z","timestamp":1780508982339,"version":"3.54.1"},"reference-count":60,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"Scientific and Technological Research Council of Turkey","doi-asserted-by":"publisher","award":["119S688"],"award-info":[{"award-number":["119S688"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004410","name":"Scientific and Technological Research Council of Turkey","doi-asserted-by":"publisher","award":["119S162"],"award-info":[{"award-number":["119S162"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The optimal function of the Na,K-ATPase (NKA) pump is essential for the heart. In ischemic heart disease, NKA activity decreases due to the decreased expression of the pump subunits. Here, we tested whether the hypoxia-inducible transcription factor (HIF-1\u03b1), the key signaling molecule regulating the adaptation of cells to hypoxia, is involved in controlling the expression and cellular dynamics of \u03b11- and \u03b21-NKA isoforms and of NKA activity in in-vitro hypoxic H9c2 cardiomyoblasts. HIF-1\u03b1 was silenced through adenoviral infection, and cells were kept in normoxia (19% O2) or hypoxia (1% O2) for 24 h. We investigated the mRNA and protein expression of \u03b11-, \u03b21-NKA using RT-qPCR and Western blot in whole-cell lysates, cell membranes, and cytoplasmic fractions after labeling the cell surface with NHS-SS-biotin and immunoprecipitation. NKA activity and intracellular ATP levels were also measured. We found that in hypoxia, silencing HIF-1\u03b1 prevented the decreased mRNA expression of \u03b11-NKA but not of \u03b21-NKA. Hypoxia decreased the plasma membrane expression of \u03b11-NKA and \u03b21- NKA compared to normoxic cells. In hypoxic cells, HIF-1\u03b1 silencing prevented this effect by inhibiting the internalization of \u03b11-NKA. Total protein expression was not affected. The decreased activity of NKA in hypoxic cells was fully prevented by silencing HIF-1\u03b1 independent of cellular ATP levels. This study is the first to show that in hypoxic H9c2 cardiomyoblasts, HIF-1\u03b1 controls the internalization and membrane insertion of \u03b11-NKA subunit and of NKA activity. The mechanism behind this regulation needs further investigation.<\/jats:p>","DOI":"10.3390\/cimb45100522","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T03:14:32Z","timestamp":1697080472000},"page":"8277-8288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hypoxia and HIF-1\u03b1 Regulate the Activity and Expression of Na,K-ATPase Subunits in H9c2 Cardiomyoblasts"],"prefix":"10.3390","volume":"45","author":[{"given":"Beyza","family":"Gurler","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4873-5554","authenticated-orcid":false,"given":"Gizem","family":"Gencay","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Biomedicine, Institute of Natural and Applied Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6786-3674","authenticated-orcid":false,"given":"Emel","family":"Baloglu","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/0006-3002(57)90343-8","article-title":"The influence of some cations on an adenosine triphosphatase from peripheral nerves","volume":"23","author":"Skou","year":"1957","journal-title":"Biochim. 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