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Dual Oxidase 2 in Lung Epithelia Is Essential for Hyperoxia-Induced Acute Lung Injury in Mice

Authors
 Kim Min-Ji  ;  Ryu Jae-Chan  ;  Kwon Younghee  ;  Lee Suhee  ;  Bae Yun Soo  ;  Yoon Joo-Heon  ;  Ryu Ji-Hwan 
Citation
 ANTIOXIDANTS & REDOX SIGNALING, Vol.21(13) : 1803-1818, 2014 
Journal Title
 ANTIOXIDANTS & REDOX SIGNALING 
ISSN
 1523-0864 
Issue Date
2014
MeSH
Acute Lung Injury/metabolism* ; Acute Lung Injury/pathology ; Animals ; Caspases/metabolism ; Cell Death/physiology ; Dual Oxidases ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Hyperoxia/metabolism* ; Lung/cytology ; Lung/metabolism* ; MAP Kinase Signaling System/physiology ; Mice ; NADPH Oxidases/metabolism* ; Oxidative Stress/physiology ; Phosphorylation/physiology ; Reactive Oxygen Species/metabolism
Abstract
Aims: Acute lung injury (ALI) induced by excessive hyperoxia has been employed as a model of oxidative stress imitating acute respiratory distress syndrome. Under hyperoxic conditions, overloading quantities of reactive oxygen species (ROS) are generated in both lung epithelial and endothelial cells, leading to ALI. Some NADPH oxidase (NOX) family enzymes are responsible for hyperoxia-induced ROS generation in lung epithelial and endothelial cells. However, the molecular mechanisms of ROS production in type II alveolar epithelial cells (AECs) and ALI induced by hyperoxia are poorly understood. Results: In this study, we show that dual oxidase 2 (DUOX2) is a key NOX enzyme that affects hyperoxia-induced ROS production, particularly in type II AECs, leading to lung injury. In DUOX2 mutant mice (DUOX2thyd/thyd) or mice in which DUOX2 expression is knocked down in the lungs, hyperoxia-induced ALI was significantly lower than in wild-type (WT) mice. DUOX2 was mainly expressed in type II AECs, but not endothelial cells, and hyperoxia-induced ROS production was markedly reduced in primary type II AECs isolated from DUOX2thyd/thyd mice. Furthermore, DUOX2-generated ROS are responsible for caspase-mediated cell death, inducing ERK and JNK phophorylation in type II AECs. Innovation: To date, no role for DUOX2 has been defined in hyperoxia-mediated ALI despite it being a NOX homologue and major ROS source in lung epithelium. Conclusion: Here, we present the novel finding that DUOX2-generated ROS induce AEC death, leading to hyperoxia-induced lung injury.
Files in This Item:
T201403673.pdf Download
DOI
10.1089/ars.2013.5677
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터) > 1. Journal Papers
Yonsei Authors
Kwon, Younghee(권영희)
Kim, Min Ji(김민지)
Ryu, Jae Chan(류재찬)
Ryu, Ji Hwan(유지환)
Yoon, Joo Heon(윤주헌)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100120
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