title: Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells.
abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H2O2) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H2O2 treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270, Republic of Korea.
authors.forename: Jung Ar
authors.initials: JA
authors.lastname: Shin
authors.forename: Jin Sil
authors.initials: JS
authors.lastname: Chung
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Cho
authors.forename: Hyung Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Young Do
authors.initials: YD
authors.lastname: Yoo
mesh_terms: D016923:Cell Death; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000166:cytology / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C513338:ROMO1 protein, human; D017382:Reactive Oxygen Species
keywords: Idiopathic pulmonary fibrosis; Lung injury; Oxidative stress; Reactive oxygen species; Romo1