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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,11,21]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Exposure to hypoxia requires adaptive mechanisms for survival. During acute hypoxia, Na,K-ATPase endocytosis in alveolar epithelial cells occurs via protein kinase C zeta (PKC\u03b6) phosphorylation of \u03b1\n                    <jats:sub>1<\/jats:sub>\n                    -Na,K-ATPase independently of the hypoxia-inducible factor (HIF). However, exaggerated Na,K-ATPase down-regulation leads to cell death. Here we report that during prolonged hypoxia plasma membrane Na,K-ATPase levels were maintained at \u223c50% of normoxic values due to HIF-mediated up-regulation of HOIL-1L, which targets PKC\u03b6 for degradation. Silencing HOIL-1L in the lung epithelium prevented PKC\u03b6 degradation, causing Na,K-ATPase downregulation. Accordingly, HIF regulation of HOIL-1L targets the phosphorylated PKC\u03b6 for degradation and serves as an hypoxia-adaptive mechanism to stabilize the Na,K-ATPase, avoiding significant lung injury.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1713563114","type":"journal-article","created":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T15:20:59Z","timestamp":1509981659000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["HIF and HOIL-1L\u2013mediated PKC\u03b6 degradation stabilizes plasma membrane Na,K-ATPase to protect against hypoxia-induced lung injury"],"prefix":"10.1073","volume":"114","author":[{"given":"Natalia D.","family":"Magnani","sequence":"first","affiliation":[{"name":"Pulmonary and Critical Care Division, Northwestern Feinberg School of Medicine, Chicago, IL, 60611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Dada","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Northwestern Feinberg School of Medicine, Chicago, IL, 60611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus A.","family":"Queisser","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Northwestern Feinberg School of Medicine, Chicago, IL, 60611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia L.","family":"Brazee","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Northwestern Feinberg School of Medicine, Chicago, IL, 60611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1666-3696","authenticated-orcid":false,"given":"Lynn C.","family":"Welch","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Northwestern Feinberg School of Medicine, Chicago, IL, 60611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishore R.","family":"Anekalla","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Northwestern Feinberg School of Medicine, Chicago, IL, 60611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Northwestern Feinberg School of Medicine, Chicago, IL, 60611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Vagin","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine, Los Angeles, CA 10833;"},{"name":"University of California at Los Angeles and Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander V.","family":"Misharin","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Northwestern Feinberg School of Medicine, Chicago, IL, 60611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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