Anti-benzopyrene-7,8-diol-9,10-epoxide induces apoptosis via mitochondrial pathway in human bronchiolar epithelium cells independent of the mitochondria permeability transition pore
Anti-benzopyrene-7,8-diol-9,10-epoxide induces apoptosis via mitochondrial pathway in human bronchiolar epithelium cells independent of the mitochondria permeability transition pore
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抗苯并芘-7,8-二醇-9,10-环氧化物通过线粒体途径诱导人细支气管上皮细胞凋亡，不依赖于线粒体通透性转换孔
DOI：
10.1016/j.fct.2012.04.041
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发表时间：
2012-07-01
影响因子：
4.3
通讯作者：
Li, Jue
中科院分区：
文献类型：
--
作者：
Sang, Hao;Zhang, Lijuan;Li, Jue
抗苯并[a]芘-7,8-二醇-9,10-环氧化物（BPDE）是烟草烟雾、汽车尾气和烧烤食品中普遍存在的环境污染物。 BPDE 对动物的致癌性已得到充分表征，但其细胞凋亡作用尚不明确。最近的一项研究表明，BPDE 介导的细胞凋亡途径在不同细胞系中具有不同的特异性。鳞状细胞癌（SCC）起源于细支气管上皮细胞，因此，我们着手研究 BPDE 对人细支气管上皮细胞（16HBE）的肺毒性和凋亡作用。我们的结果表明，BPDE 在 16HBE 细胞中以剂量依赖性方式诱导线粒体介导的细胞凋亡。 caspase-3,-9 的裂解和细胞色素 c (cyt c) 的释放在细胞凋亡刺激过程中受到调节。然而，尚未检测到线粒体通透性转换孔（mPTP）的开放。此外，我们的数据还表明，活性氧 (ROS) 的形成、线粒体膜电位 (Delta Psi(m)) 的下降、p53 的增加和 c-Myc 水平的降低在 BPDE 毒性反应中发挥着重要作用。总之，这些结果表明，BPDE 介导的细胞凋亡是通过与 ROS 形成、Delta Psi(m) 缺失、p53 上调和 c-Myc 下调相关的 caspase-9 依赖性线粒体途径发生的，但与 16HBE 细胞中 mPTP 的开放无关。 (C) 2012 Elsevier Ltd. 保留所有权利。
Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a ubiquitous environmental pollutant contained in tobacco smoke, automobile exhausts and barbecued foods. The carcinogenicity of BPDE on animals has been well characterized, whereas its apoptotic effect is not well defined. A recent study has shown that BPDE-mediated apoptotic pathway has varying specificity across different cell lines. Squamous cell carcinoma (SCC) arises from bronchiolar epithelium cells, therefore, we set out to investigate the pulmonary toxicity and apoptotic effect of BPDE in human bronchiolar epithelium cells (16HBE). Our results show BPDE induces mitochondrial-mediated apoptosis in a dose-dependent manner in 16HBE cells. The cleavage of caspase-3,-9 and release of Cytochrome c (cyt c) was regulated during apoptotic stimulation. However, the opening of mitochondria permeability transition pore (mPTP) has not been detected. Furthermore, our data also indicate that the formation of reactive oxygen species (ROS), decline of mitochondrial membrane potential (Delta Psi(m)), increasing p53 and decreasing c-Myc levels play important roles in response to BPDE toxicity. In conclusion, these results suggest that BPDE-mediated apoptosis occurs via caspase-9 dependent mitochondria pathway associated with ROS formation, loss of Delta Psi(m) up-regulation of p53 and down-regulation of c-Myc, but independent of the opening of mPTP in 16HBE cells. (C) 2012 Elsevier Ltd. All rights reserved.