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Nadph oxidase production of O2‐ increases epithelial sodium channel (ENaC) activity and regulates lung fluid clearance in vivo
Author(s) -
Goodson Preston,
Kumar Amrita,
Helms My N
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1039.34
Subject(s) - epithelial sodium channel , lung , in vivo , nadph oxidase , chemistry , rac1 , endocrinology , medicine , pharmacology , sodium , biology , oxidative stress , biochemistry , signal transduction , microbiology and biotechnology , organic chemistry
We have recently shown that Rac‐1 mediated‐NOX2 release of O 2 − has a permissive effect on epithelial sodium channel (ENaC) activity. The objective of this study was to determine whether changes in single channel ENaC recordings indeed translate into significant changes in lung fluid clearance. Using a novel fluoroscopic assay for measuring lung fluid volume in vivo , we showed that NSC23766 inhibition of Rac1 in 3 month old C57Bl6 mice significantly decreased fluid clearance (n=7) compared to untreated control animals (n=10). Similarly, fluid challenged gp91phox −/− knock out mice (−/−Cybb; n=7) failed to clear lung fluid compared to age matched control (n=8). We also show for the first time that inhibition of Rac1 decreases the oxidative state of the lung using novel redox sensitive hydrocyanine compounds (n=3). In conclusion, our results indicate that targeting small G protein Rac1 and NOX2 production of O 2 − may be a useful therapeutic for treating several various lung disorders.