Rac1/Tiam1-mediated Nadph oxidase activation of epithelial sodium channels regulates neonatal lung aeration and alveolar development Open Access

Trac, David Quoc (2013)

Permanent URL: https://etd.library.emory.edu/concern/etds/4f16c300g?locale=en
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Abstract

Preterm infants have higher incidence of respiratory failure than term infants. These respiratory disorders are caused in part by delayed clearance of lung fluid at birth. At birth, lung fluid clearance and aeration and mediated by active salt and water transport by epithelial sodium channel (ENaC) activity. Our lab has shown that oxidative environments can enhance ENaC activity, most likely via Nadph oxidase (Nox)-mediated O2- release. In this highly regulated process, we have shown that the small G-protein Rac1 plays an important role upstream of Nox signaling. However, the Rac1-guanine nucleotide exchange factors (GEFs) involved in the neonatal Nox-ENaC signaling process are unknown. Additionally, the role of ENaC in the postnatal developing lung has yet to be explored. Herein, we utilized real-time PCR and confocal immunohistochemistry to identify Tiam1 as the main GEF involved in the mediation of Rac1-activation of Nox and downstream ENaC activity. Additionally, we paired inhibitory drugs with morphological and functional analyses to elucidate a novel role of the Rac1/Tiam1-mediated Nox-ENaC signaling pathway in postnatal alveolar development.

Table of Contents

Introduction............................................................................................1

Methods.................................................................................................3

Results.................................................................................................10

Discussion.............................................................................................14

References............................................................................................19

Figures..................................................................................................26

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