Role of ubiquitination in Na,K-ATPase regulation during lung injury.
During acute lung injury edema accumulates in the alveolar space, resulting in hypoxemia due to intrapulmonary shunt. The alveolar Na,K-ATPase, by effecting active Na(+) transport, is essential for removing edema from the alveolar spaces. However, during hypoxia it is endocytosed and degraded, which results in decreased Na,K-ATPase function and impaired lung edema clearance. Na,K-ATPase endocytosis and degradation require the phosphorylation and subsequent ubiquitination of the Na,K-ATPase. These events are the results of cross-talk between post-translational modifications, and how ubiquitination of a specific protein can result from injurious extracellular stimuli. Here, we review current knowledge on the regulation of Na,K-ATPase activity during lung injury, focusing on the role of Na,K-ATPase ubiquitination during hypoxia. A better understanding of these signaling pathways can be of relevance for the design of novel treatments to ameliorate the deleterious effects of acute lung injury.
Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, 240 E. Huron, McGaw Pavilion M-300, Chicago, IL 60611, USA.
Iiro T
IT
Helenius
Laura A
LA
Dada
Jacob I
JI
Sznajder
D000818:Animals; D015536:Down-Regulation; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D010766:Phosphorylation; D011650:Pulmonary Alveoli / Q000201:enzymology; D011654:Pulmonary Edema / Q000201:enzymology* / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000201:enzymology* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000201:enzymology* / Q000473:pathology; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
D025801:Ubiquitin; D000254:Sodium-Potassium-Exchanging ATPase