Asbestos induces apoptosis of human and rabbit pleural mesothelial cells via reactive oxygen species
Asbestos induces apoptosis of human and rabbit pleural mesothelial cells via reactive oxygen species
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DOI：
10.1172/jci119010
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发表时间：
1996-11-01
影响因子：
15.9
通讯作者：
Boylan, AM
中科院分区：
文献类型：
--
作者：
Broaddus, VC;Yang, L;Boylan, AM
间皮细胞是石棉诱导的肿瘤间皮瘤的祖细胞，对石棉的毒性作用特别敏感，尽管石棉诱导间皮细胞损伤的分子机制尚不清楚，我们询问石棉是否诱导间皮细胞凋亡以及活性氧是否重要。胸膜间皮细胞（兔子或人）暴露于石棉（青石棉、铁石棉或温石棉）或中等剂量的对照颗粒（1-10 μ g/cm（2））24小时，并评价寡核小体DNA断裂、膜磷脂不对称性丧失和核浓缩、天冬氨酸纤维，而不是对照颗粒，通过所有试验诱导间皮瘤细胞凋亡，并且对于所有类型的石棉，（5 μ g/cm（2））诱导15.0+/-1.1%（平均值+/-SE; n = 12）细胞凋亡，而对照颗粒<4%。细胞外过氧化氢酶、超氧化物歧化酶、缺氧（8%氧）、去铁胺、3-氨基苯甲酰胺[聚（ADP-核糖基）聚合酶抑制剂]和细胞松弛素B。只有过氧化氢酶和细胞松弛素B降低纤维摄取。我们认为石棉通过活性氧诱导间皮细胞凋亡，逃避这一途径可能允许石棉诱导突变的间皮细胞异常存活。
Mesothelial cells, the progenitor cell of the asbestos-induced tumor mesothelioma, are particularly sensitive to the toxic effects of asbestos, although the molecular mechanisms by which asbestos induces injury in mesothelial cells are not known, We asked whether asbestos induced apoptosis in mesothelial cells and whether reactive oxygen species were important. Pleural mesothelial cells (rabbit or human) were exposed to asbestos (crocidolite, amosite, or chrysotile) or control particles at moderate doses (1-10 mu g/cm(2)) over 24 h and evaluated for oligonucleosomal DNA fragmentation, loss of membrane phospholipid asymmetry, and nuclear condensation, Asbestos fibers, not control particles, induced apoptosis in mesothelial cells by all assays and induction of apoptosis was dose dependent for all types of asbestos, with crocidolite (5 mu g/cm(2)) inducing 15.0+/-1.1% (mean+/-SE; n = 12) apoptosis versus control particles < 4%. Apoptosis induced by asbestos, but not by actinomycin D, was inhibited by extracellular catalase, superoxide dismutase in the presence of catalase, hypoxia (8% oxygen.), deferoxamine, 3-aminobenzamide [an inhibitor of poly(ADP-ribosyl) polymerase], and cytochalasin B. Only catalase and cytochalasin B decreased fiber uptake, We conclude that asbestos induces apoptosis in mesothelial cells via reactive oxygen species, Escape from this pathway could allow the abnormal survival of mesothelial cells with asbestos-induced mutations.