The JNK signaling pathway mediates chrysotile asbestos-inducedalveolar epithelial cell apoptosis
作者单位：广东医学院附属医院临床医学研究中心
会议名称：《中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议》
会议日期：2014年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：chrysotile asbestos apoptosis c Jun N terminal kinases(JNK) mitochondriald ysfunction
摘 要：Chrysotile asbestos exposure is associated with excess mortality from pulmonary diseasessuch as lung cancer, mesothelioma, and asbestosis. Although multiple mechanisms bywhich chrysotile asbestos fibers induce pulmonary disease have been identified, the roleof apoptosis in human lung alveolar epithelial cells(AEC) has not been fully explored. Accumulatingevidence implicate AEC apoptosis as a crucial event in the development ofidiopathic pulmonary fibrosis(IPF) as well as asbestosis. The goal of this study was to determinewhether chrysotile asbestos induces mitochondria-regulated(intrinsic) AEC apoptosisand, if so, whether this occurs via activation of mitogen-activated protein kinases(MAPK). Using human A549 bronchoalveolar carcinoma-derived cells with alveolar epithelialtype II-like features, we show that chrysotile asbestos induces a dose/timedependentdecrease in cell viability, which is accompanied by the activation of the MAPKc-Jun N-terminal kinases(JNK), but not the MAPKs extracellular signal-regulated kinase(ERK)1/2 and p38. Chrysotile asbestos induces intrinsic AEC apoptosis as evidenced by theup-regulation of pro-apoptotic Bax and Bak along with activation of caspase-9, poly(ADPribose)polymerase(PARP), and cytochrome c release. Notably, SP600125, a specific JNKinhibitor, blocked chrysotile asbestos-induced JNK activation and apoptosis as assessed byboth caspase-9 cleavage and PARP activation. Our results demonstrate that chrysotile asbestosinduces intrinsic AEC apoptosis by a JNK-dependent mechanism and suggests apotential novel target for modulating chrysotile asbestos-related lung diseases.