caa a22 4500 463208471 CHVBK 20180405153133.0 cr unu---uuuuu 170326e20071201xx s 000 0 eng 10.1007/s10863-007-9102-1 doi (NATIONALLICENCE)springer-10.1007/s10863-007-9102-1 Regulation of Na,K-ATPase during acute lung injury [Elektronische Daten] [Emilia Lecuona, Humberto Trejo, Jacob Sznajder] A hallmark of acute lung injury is the accumulation of a protein rich edema which impairs gas exchange and leads to hypoxemia. The resolution of lung edema is effected by active sodium transport, mostly contributed by apical Na+ channels and the basolateral located Na,K-ATPase. It has been reported that the decrease of Na,K-ATPase function seen during lung injury is due to its endocytosis from the cell plasma membrane into intracellular pools. In alveolar epithelial cells exposed to severe hypoxia, we have reported that increased production of mitochondrial reactive oxygen species leads to Na,K-ATPase endocytosis and degradation. We found that this regulated process follows what is referred as the Phosphorylation-Ubiquitination-Recognition-Endocytosis-Degradation (PURED) pathway. Cells exposed to hypoxia generate reactive oxygen species which activate PKCζ which in turn phosphorylates the Na,K-ATPase at the Ser18 residue in the N-terminus of the α1-subunit leading the ubiquitination of any of the four lysines (K16, K17, K19, K20) adjacent to the Ser18 residue. This process promotes the α1-subunit recognition by the μ2 subunit of the adaptor protein-2 and its endocytosis trough a clathrin dependent mechanism. Finally, the ubiquitinated Na,K-ATPase undergoes degradation via a lysosome/proteasome dependent mechanism. Springer Science+Business Media, LLC, 2007 Acute lung injury nationallicence Na,K-ATPase nationallicence Alveolar epithelium nationallicence Lecuona Emilia Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, 60611, Chicago, IL, USA aut Trejo Humberto Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, 60611, Chicago, IL, USA aut Sznajder Jacob Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, 60611, Chicago, IL, USA aut Journal of Bioenergetics and Biomembranes Springer US; http://www.springer-ny.com 39/5-6(2007-12-01), 391-395 0145-479X 39:5-6<391 2007 39 10863 https://doi.org/10.1007/s10863-007-9102-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10863-007-9102-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lecuona Emilia Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, 60611, Chicago, IL, USA aut NATIONALLICENCE 700 1- Trejo Humberto Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, 60611, Chicago, IL, USA aut NATIONALLICENCE 700 1- Sznajder Jacob Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, 60611, Chicago, IL, USA aut NATIONALLICENCE 773 0- Journal of Bioenergetics and Biomembranes Springer US; http://www.springer-ny.com 39/5-6(2007-12-01), 391-395 0145-479X 39:5-6<391 2007 39 10863 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer