title: Pro-apoptotic Noxa is involved in ablative focal irradiation-induced lung injury.
abstract: Although lung injury including fibrosis is a well-documented side effect of lung irradiation, the mechanisms underlying its pathology are poorly understood. X-rays are known to cause apoptosis in the alveolar epithelial cells of irradiated lungs, which results in fibrosis due to the proliferation and differentiation of fibroblasts and the deposition of collagen. Apoptosis and BH3-only pro-apoptotic proteins have been implicated in the pathogenesis of pulmonary fibrosis. Recently, we have established a clinically analogous experimental model that reflects focal high-dose irradiation of the ipsilateral lung. The goal of this study was to elucidate the mechanism underlying radiation-induced lung injury based on this model. A radiation dose of 90 Gy was focally delivered to the left lung of C57BL/6 mice for 14 days. About 9 days after irradiation, the mice began to show increased levels of the pro-apoptotic protein Noxa in the irradiated lung alongside increased apoptosis and fibrosis. Suppression of Noxa expression by small interfering RNA protected cells from radiation-induced cell death and decreased expression of fibrogenic markers. Furthermore, we showed that reactive oxygen species participate in Noxa-mediated, radiation-induced cell death. Taken together, our results show that Noxa is involved in X-ray-induced lung injury.
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jee-Youn
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: An
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Won Hoon
authors.initials: WH
authors.lastname: Choi
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jin-Mo
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Samju
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Byung Rok
authors.initials: BR
authors.lastname: Yoo
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jeong Wook
authors.initials: JW
authors.lastname: Kang
authors.affiliation: College of Pharmacy and Division of Life and Pharmaceutical Science, Ewha Womans University, Seoul, South Korea.
authors.forename: Yun-Sil
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jaeho
authors.initials: J
authors.lastname: Cho
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology / Q000528:radiation effects; D055370:Lung Injury / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011832:Radiation Injuries / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014965:X-Rays
chemical_list: D015415:Biomarkers; C498702:PMAIP1 protein, human; C408009:Pmaip1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species
keywords: Noxa; apoptosis; lung injury; radiation