Summary of project PR001641

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001641. The data can be accessed directly via it's Project DOI: 10.21228/M8KM6N This work is supported by NIH grant, U2C- DK119886.


Project ID: PR001641
Project DOI:doi: 10.21228/M8KM6N
Project Title:Myeloperoxidase oxidants elicit distinct metabolomic responses in airway epithelial cells and reveal early cystic fibrosis disease risk factors
Project Summary:Myeloperoxidase (MPO) is released by neutrophils in inflamed tissues. MPO oxidizes chloride, bromide, and thiocyanate to produce hypochlorous acid (HOCl), hypobromous acid (HOBr), or hypothiocyanous acid (HOSCN), respectively. These oxidants are toxic to pathogens, but they also react with host cells and may elicit redox signaling or cause collateral damage. Here, we investigated how equal dose-rate exposures of MPO-derived oxidants differentially impact the metabolome of human airway epithelial cells (AEC). AECs are important targets of oxidative stress in inflammatory lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease, in which neutrophils, MPO, and reactive oxygen species are increased compared to healthy individuals. HOSCN-exposed cells were viable after 24 h of continuous oxidant exposure, while HOBr and HOCl exposures were cytotoxic by 24 h. Untargeted metabolomics revealed MPO-derived oxidants caused distinct metabolic effects in AECs. HOCl and HOBr were more similar to each other than either was to HOSCN, and all differed from hydrogen peroxide. We noted methionine oxidation products, methionine sulfoxide and dehydromethionine, were significantly increased compared to controls only in HOCl- and HOBr-exposed cells. Furthermore, the presence of these metabolites in bronchoalveolar lavage fluid from 5 years-olds with CF (n=27) was associated with increased neutrophilic inflammation and bronchiectasis. This indicates that HOCl and/or HOBr are likely present in early CF airways and either contribute to disease progression or associate with a related pathophysiological process. We anticipate this oxidant exposure model can be used to identify additional novel metabolites which could serve as candidate biomarkers of MPO-driven inflammation in human disease.
Institute:Emory University
Laboratory:Joshua Chandler, PhD
Last Name:Chandler
First Name:Joshua
Address:2015 Uppergate Drive, Atlanta, GA 30322
Contributors:Joshua Chandler, Susan Kim

Summary of all studies in project PR001641

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST002548 Equal Flux of Oxidants study Homo sapiens Emory University MS* 2023-09-19 1 385 Uploaded data (192.7G)*