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.
Helenius
Iiro T
IT
Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, 240 E. Huron, McGaw Pavilion M-300, Chicago, IL 60611, USA.
Dada
Laura A
LA
Sznajder
Jacob I
JI
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