{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:05:45Z","timestamp":1791219945908,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,12,11]],"date-time":"2007-12-11T00:00:00Z","timestamp":1197331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:p>\n                    Hypoxia inhibits Na\u2010K\u2010ATPase activity and leads to its degradation in mammalian cells. Von Hippel Lindau protein (pVHL) and hypoxia inducible factor (HIF) are key mediators in cellular adaptation to hypoxia; thus, we set out to investigate whether pVHL and HIF participate in the hypoxia\u2010mediated degradation of plasma membrane Na\u2010K\u2010ATPase. We found that in the presence of pVHL hypoxia decreased Na\u2010K\u2010 ATPase activity and promoted the degradation of plasma membrane Na\u2010K\u2010ATPase. In pVHL\u2010deficient cells, hypoxia did not decrease the Na\u2010K\u2010ATPase activ ity and the degradation of plasma membrane Na\u2010K\u2010 ATPase was prevented. pVHL\u2010mediated degradation of Na\u2010K\u2010ATPase required the functional pVHL E3 ligase and Ubc5 since pVHL mutants and dominant negative Ubc5 prevented Na\u2010K\u2010ATPase from degradation. The generation of reactive oxygen species was necessary for pVHL\u2010mediated Na\u2010K\u2010ATPase degradation during hypoxia. Desferrioxamine, which stabilizes HIF1\/2\u03b1, did not affect the half\u2010life of plasma mem brane Na\u2010K\u2010ATPase. In addition, stabilizing HIF1\/2\u03b1 by infecting mammalian cells with adenoviruses con taining the oxygen\u2010dependent degradation domain of HIFl\u03b1 did not affect the plasma membrane Na\u2010K\u2010 ATPase degradation. In cells with suppression of pVHL by short hairpin RNA, the Na\u2010K\u2010ATPase was not de graded during hypoxia, whereas cells with knockdown of HIF1\/2\u03b1 retained the ability to degrade plasma membrane Na\u2010K\u2010ATPase. These findings suggest that pVHL participates in the hypoxia\u2010mediated degradation of plasma membrane Na\u2010K\u2010ATPase in a HIF\u2010 independent manner.\u2014Zhou, G., Dada, L. A., Chandel, N. S., Iwai, K., Lecuona, E., Ciechanover, A., Sznajder, J. I. Hypoxia\u2010mediated Na\u2010K\u2010ATPase degradation re quires von Hippel Lindau protein.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 22, 1335\u20131342 (2008)\n                  <\/jats:p>","DOI":"10.1096\/fj.07-8369com","type":"journal-article","created":{"date-parts":[[2007,12,11]],"date-time":"2007-12-11T23:48:37Z","timestamp":1197416917000},"page":"1335-1342","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Hypoxia\u2010mediated Na\u2010K\u2010ATPase degradation requires von Hippel Lindau protein"],"prefix":"10.1096","volume":"22","author":[{"given":"Guofei","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Feinberg School of Medicine Northwestern University Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Dada","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Feinberg School of Medicine Northwestern University Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navdeep S.","family":"Chandel","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Feinberg School of Medicine Northwestern University Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Iwai","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology Graduate School of Medicine Osaka City University Abeno\u2010Ku Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Lecuona","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Feinberg School of Medicine Northwestern University Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Ciechanover","sequence":"additional","affiliation":[{"name":"Vascular and Tumor Biology Research Center Faculty of Medicine Technion\u2010Israel Institute of Technology Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob I.","family":"Sznajder","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Feinberg School of Medicine Northwestern University Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,12,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1095-6433(00)00234-8"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.275.5.F633"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.71.102201.141218"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63747-9"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.12.5510"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00770.2003"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059796"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.22.12436"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5413.455"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.05.001"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1252404"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203344200"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.18.5197"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059817"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.25.5.4420"},{"key":"e_1_2_6_17_1","first-page":"L70","article-title":"Inhibition of Na\u2010K\u2010ATPase activity after prolonged hypoxia in an alveolar epithelial cell line","volume":"271","author":"Planes C.","year":"1996","journal-title":"Am. 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