Journal article
The pH-sensitive translocation of V-ATPase in the small airway of cystic fibrosis pigs
American journal of physiology. Lung cellular and molecular physiology, Vol.327(5), pp.L749-L755
11/01/2024
DOI: 10.1152/ajplung.00147.2024
PMCID: PMC11563583
PMID: 39254087
Abstract
In contrast to pig large airways, the pH of airway surface liquid (ASL) in pig small airways is regulated by CFTR mediated HCO - 3 secretion and the vacuolar-type H + ATPase (V-ATPase) proton secretion. We hypothesized that in Cystic Fibrosis (CF), the ASL pH of small airways is acidic, and the V-ATPase is internalized. We quantified proton secretion during the addition of an alkaline test solutions by measuring changes in a pH dependent fluorescent dye generated by porcine small airway epithelia in the absence and presence of bafilomycin A1. The pH-dependent translocation of V-ATPase in ex vivo and in vivo preparations was measured using immunolocalization of V-ATPase. We found that bafilomycin sensitive proton secretion stopped when the ASL pH was less than 7.10. In non-CF pigs and mice, we found that V-ATPase was localized in the apical membrane, and internalized when the lungs were instilled with a pH 6.8 solution.Studies where we immediately fixed lungs from pigs revealed apical V-ATPase detection in non-CF piglets and less apical detection in CF piglets. Our data suggest that V-ATPase in small airways is internalized when the ASL pH is acidic. The decrease in apical localization of V-ATPase in CF pigs is consistent with an acidic ASL pH.
Details
- Title: Subtitle
- The pH-sensitive translocation of V-ATPase in the small airway of cystic fibrosis pigs
- Creators
- Raul Villacreses - University of IowaIan M. Thornell - University of IowaXiaopeng Li - University of IowaSteven E. Mather - University of IowaJimena Urbano - University of Iowa, Internal MedicineDavid A. Stoltz - University of IowaJoseph Zabner - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.327(5), pp.L749-L755
- DOI
- 10.1152/ajplung.00147.2024
- PMID
- 39254087
- PMCID
- PMC11563583
- NLM abbreviation
- Am J Physiol Lung Cell Mol Physiol
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Publisher
- AMER PHYSIOLOGICAL SOC
- Grant note
- National Center for Advancing Translational Sciences: K12TR004382 National Heart, Lung, and Blood Institute: HL153165-01A1, HL091842
This work was supported by National Center for Advancing Translational Sciences (K12TR004382 to R. V.) and National Heart, Lung, and Blood Institute (HL153165-01A1 to X.L. and J.Z.; HL091842 to R.V., I.M.T., X. L., S.E.M., J.U., D.A.S., and J.Z.).
- Language
- English
- Electronic publication date
- 09/10/2024
- Date published
- 11/01/2024
- Academic Unit
- Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984702847502771
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