Protective function of DJ-1/PARK7 in lipopolysaccharide and ventilator-induced acute lung injury

Hajera Amatullah; Tatiana Maron-Gutierrez; Yuexin Shan; Sahil Gupta; James N. Tsoporis; Amir K. Varkouhi; Ana Paula Teixeira Monteiro; Xiaolin He; Jun Yin; John C. Marshall; Patricia R.M. Rocco; Haibo Zhang; Wolfgang M. Kuebler; Claudia C. dos Santos

Redox Biology (Jan 2021)

Protective function of DJ-1/PARK7 in lipopolysaccharide and ventilator-induced acute lung injury

Hajera Amatullah,
Tatiana Maron-Gutierrez,
Yuexin Shan,
Sahil Gupta,
James N. Tsoporis,
Amir K. Varkouhi,
Ana Paula Teixeira Monteiro,
Xiaolin He,
Jun Yin,
John C. Marshall,
Patricia R.M. Rocco,
Haibo Zhang,
Wolfgang M. Kuebler,
Claudia C. dos Santos

Affiliations

Hajera Amatullah: Keenan Research Center of St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
Tatiana Maron-Gutierrez: Keenan Research Center of St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, Canada; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, RJ, Brazil
Yuexin Shan: Keenan Research Center of St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, Canada
Sahil Gupta: Keenan Research Center of St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
James N. Tsoporis: Keenan Research Center of St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, Canada
Amir K. Varkouhi: Keenan Research Center of St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, Canada
Ana Paula Teixeira Monteiro: Keenan Research Center of St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, Canada
Xiaolin He: Keenan Research Center of St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, Canada
Jun Yin: Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, 200032, China
John C. Marshall: Keenan Research Center of St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
Patricia R.M. Rocco: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, RJ, Brazil
Haibo Zhang: Keenan Research Center of St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
Wolfgang M. Kuebler: Keenan Research Center of St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
Claudia C. dos Santos: Keenan Research Center of St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada; Corresponding author. Interdepartmental Division of Critical Care, St. Michael's Hospital/University of Toronto, 30 Bond Street, Room 4-008, Toronto, ON, M5B 1WB, Canada.

Journal volume & issue: Vol. 38
p. 101796

Abstract

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Oxidative stress is considered one of the early underlying contributors of acute lung injury (ALI) and ventilator-induced lung injury (VILI). DJ-1, also known as PARK7, has a well-established role as an antioxidant. We have previously shown maintaining oxidative balance via the ATF3-Nrf2 axis was important in protection from ALI. Here, we exclusively characterize the role of DJ-1 in sterile LPS-induced ALI and VILI. DJ-1 protein expression was increased after LPS treatment in human epithelial and endothelial cell lines and lungs of wild-type mice. DJ-1 deficient mice exhibited greater susceptibility to LPS-induced acute lung injury as demonstrated by increased cellular infiltration, augmented levels of pulmonary cytokines, enhanced ROS levels and oxidized by-products, increased pulmonary edema and cell death. In a two-hit model of LPS and mechanical ventilation (MV), DJ-1 deficient mice displayed enhanced susceptibility to inflammation and lung injury. Collectively, these results identify DJ-1 as a negative regulator of ROS and inflammation, and suggest its expression protects from sterile lung injury driven by high oxidative stress.

Published in Redox Biology

ISSN: 2213-2317 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.journals.elsevier.com/redox-biology/

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