What question did this study set out to answer?

To determine the molecular mechanism by which hypoxia inhibits Na,K-ATPase activity and impairs alveolar fluid clearance in lung epithelial cells.

April 1, 2003Journal of Clinical InvestigationOpen Access

Hypoxia-induced endocytosis of Na,K-ATPase in alveolar epithelial cells is mediated by mitochondrial reactive oxygen species and PKC-ζ

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To determine the molecular mechanism by which hypoxia inhibits Na,K-ATPase activity and impairs alveolar fluid clearance in lung epithelial cells.
Exposed alveolar epithelial cells and mitochondrial DNA-deficient rho(0) cells to hypoxic conditions followed by reoxygenation.
Quantified Na,K-ATPase activity, basolateral membrane surface abundance, and control protein GLUT1 levels in the presence and absence of antioxidants.
Assessed alpha(1) subunit phosphorylation using a PKC-zeta inhibitor peptide and a mutant subunit lacking the Ser-18 phosphorylation site.
Hypoxia caused a reversible, time-dependent reduction in basolateral Na,K-ATPase alpha(1) abundance and transport activity via endocytosis without changing total cellular protein levels.
Hypoxia elevated mitochondrial reactive oxygen species, whereas antioxidant administration and mitochondrial DNA deficiency completely prevented both oxidant accumulation and Na,K-ATPase inhibition.
Disrupting PKC-zeta signaling with an antagonist peptide or introducing a Ser-18 phosphorylation-deficient alpha(1) mutant fully protected Na,K-ATPase surface expression and function under hypoxia.

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Implication

Laboratory study reveals hypoxia triggers Na,K-ATPase endocytosis in alveolar epithelial cells via mitochondrial ROS and PKC-zeta, highlighting mechanisms of impaired lung fluid clearance.

Cite This Study

Dada et al. (2003) studied this question.

synapsesocial.com/papers/69dd3a6c0644c7b49d40c6ca https://doi.org/10.1172/jci16826

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Implication

Laboratory study reveals hypoxia triggers Na,K-ATPase endocytosis in alveolar epithelial cells via mitochondrial ROS and PKC-zeta, highlighting mechanisms of impaired lung fluid clearance.

Hypoxia-induced endocytosis of Na,K-ATPase in alveolar epithelial cells is mediated by mitochondrial reactive oxygen species and PKC-ζ

Key Points

Discussion

Implication

Cite This Study

Hypoxia-induced endocytosis of Na,K-ATPase in alveolar epithelial cells is mediated by mitochondrial reactive oxygen species and PKC-ζ

Key Points

Discussion

Implication

Cite This Study

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