title: Astaxanthin inhibits apoptosis in alveolar epithelial cells type II in vivo and in vitro through the ROS-dependent mitochondrial signalling pathway.
abstract: Oxidative stress is an important molecular mechanism underlying lung fibrosis. The mitochondrion is a major organelle for oxidative stress in cells. Therefore, blocking the mitochondrial signalling pathway may be the best therapeutic manoeuver to ameliorate lung fibrosis. Astaxanthin (AST) is an excellent antioxidant, but no study has addressed the pathway of AST against pulmonary oxidative stress and free radicals by the mitochondrion-mediated signalling pathway. In this study, we investigated the antioxidative effects of AST against H2 O2 - or bleomycin (BLM)-induced mitochondrial dysfunction and reactive oxygen species (ROS) production in alveolar epithelial cells type II (AECs-II) in vivo and in vitro. Our data show that AST blocks H2 O2 - or BLM-induced ROS generation and dose-dependent apoptosis in AECs-II, as characterized by changes in cell and mitochondria morphology, translocation of apoptotic proteins, inhibition of cytochrome c (Cyt c) release, and the activation of caspase-9, caspase-3, Nrf-2 and other cytoprotective genes. These data suggest that AST inhibits apoptosis in AECs-II cells through the ROS-dependent mitochondrial signalling pathway and may be of potential therapeutic value in lung fibrosis treatment.
authors.affiliation: Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China; Medicine Research Center, Binzhou Medical University, Yantai, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Song
authors.forename: Bingsi
authors.initials: B
authors.lastname: Wang
authors.forename: Shengcui
authors.initials: S
authors.lastname: Lin
authors.forename: Lili
authors.initials: L
authors.lastname: Jing
authors.forename: Cuiping
authors.initials: C
authors.lastname: Mao
authors.forename: Pan
authors.initials: P
authors.lastname: Xu
authors.forename: Changjun
authors.initials: C
authors.lastname: Lv
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Ji
authors.initials: J
authors.lastname: Zuo
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D045304:Cytochromes c / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis / Q000188:drug therapy* / Q000473:pathology; D005609:Free Radicals; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D024341:Xanthophylls / Q000008:administration & dosage
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D017382:Reactive Oxygen Species; D024341:Xanthophylls; C005948:astaxanthine; D045304:Cytochromes c
keywords: ROS; astaxanthin; lung fibrosis; mitochondrial signalling pathway; oxidative stress