title: Enhancement of the acrolein-induced production of reactive oxygen species and lung injury by GADD34.
abstract: Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS). Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury.
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan ; Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Nishio
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Lintao
authors.identifier: 0000-0002-7984-194X
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Isobe
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D007249:Inflammation; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000171:Acrolein; D017346:Protein Serine-Threonine Kinases; C531557:eIF2alpha kinase, mouse; C513256:Ppp1r15a protein, mouse; D054645:Protein Phosphatase 1; D000111:Acetylcysteine
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