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

doi:10.1016/j.redox.2020.101796

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

Redox Biol. 2021 Jan:38:101796. doi: 10.1016/j.redox.2020.101796. Epub 2020 Nov 17.

Affiliations

¹ 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.
² 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.
³ Keenan Research Center of St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, Canada.
⁴ 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.
⁵ Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
⁶ Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, RJ, Brazil.
⁷ 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.
⁸ 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. Electronic address: Claudia.DosSantos@unityhealth.to.

Abstract

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.

Keywords: Acute lung injury; DJ-1; PARK7; VILI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Lung Injury* / genetics
Animals
Cell Line
Humans
Lipopolysaccharides
Lung
Mice
Mice, Inbred C57BL
Protein Deglycase DJ-1* / genetics
Ventilator-Induced Lung Injury* / genetics
Ventilators, Mechanical

Substances

Lipopolysaccharides
PARK7 protein, mouse
Protein Deglycase DJ-1

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

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

Grants and funding