# Oxidized glutathione regulation of epithelial sodium channels in newborn lung injury

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $384,436

## Abstract

Project Summary/Abstract
Epithelial sodium channels (ENaC) serve as the rate limiting step in net salt and water removal from the airspace
by generating osmotic gradients for subsequent water transport. In the lung, the regulation of ENaC is fine-tuned
so that a precise volume of water continually lines the airway epithelium, which keeps the lungs appropriately
moist for effective gas exchange. In some patients with lung injury, it is not clear why lung ENaC fails to function.
Normal ENaC activity is critically important in preterm infants, since they are born with immature lung, low levels
of ENaC protein, and often require oxygen supplementation. In this study, we look at whether oxygen
supplementation (hyperoxia) confounds lung injury by turning off ENaC. We use a term mouse model of
hyperoxia induced oxidative stress in our studies. Our rationale is that under high oxygen, the antioxidant
glutathione is oxidized to its disulfide form, termed GSSG. Our preliminary data indicates that GSSG can alter
ENaC function through direct post translational modification of conserved Cys thiols on ENaC, albeit the modified
Cys have not been mapped. Whether GSSG modifies ENaC under a biologically relevant model of hyperoxia
induced lung injury has not been evaluated. Our goal is to delineate biologically relevant post-translational
modification of lung ENaC by GSSG and determine whether lowering lung GSSG levels can improve health
outcomes for preterm infants requiring oxygen supplementation.

## Key facts

- **NIH application ID:** 9936061
- **Project number:** 5R01HL137033-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** My N. Helms
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $384,436
- **Award type:** 5
- **Project period:** 2018-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936061

## Citation

> US National Institutes of Health, RePORTER application 9936061, Oxidized glutathione regulation of epithelial sodium channels in newborn lung injury (5R01HL137033-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9936061. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*