Manganese activates caspase-9-dependent apoptosis in human bronchial epithelial cells-猫眼课题宝

锰激活人支气管上皮细胞中 caspase-9 依赖性细胞凋亡

DOI：

10.1177/0960327112470272

发表时间：

2013-11

期刊：

Human & Experimental Toxicology

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

张丽娟;桑灏;刘艺敏;李觉

急性吸入暴露于高水平的锰（Mn）与肺水肿和功能受损有关。Mn在体内和体外实验中的免疫介导的肺上皮损伤已得到很好的表征，而其凋亡作用尚未得到很好的定义。我们的研究结果表明，人支气管上皮细胞（16 HBE）进行半胱天冬酶-9介导的细胞死亡的锰。在此过程中，线粒体膜电位（Δ Vm）的丧失、活性氧的形成和细胞色素c的释放受到调节。此外，c-Myc水平降低、磷酸化p53（Ser 15）和WAF 1/p21表达增加也参与了锰的肺毒性作用。蛋白酶体抑制剂MG 132可增加c-Myc蛋白的表达。综上所述，我们的研究结果表明，caspase-9依赖的内源性通路、c-Myc的下调以及p53和磷酸化p53的上调可能是锰诱导16 HBE细胞凋亡的机制之一。此外，c-Myc减少可能是由于通过泛素-蛋白酶体途径的降解增加。

Acute inhalation exposure to high levels of manganese (Mn) is associated with pulmonary edema and impaired function. The immune-mediated lung epithelium injury of Mn in vivo and in vitro experiments has been well characterized, whereas its apoptotic effect is not well defined. Our results show that human bronchial epithelial (16HBE) cells undergo caspase-9-mediated cell death in response to Mn. Loss of mitochondrial membrane potential (ΔΨm), the formation of reactive oxygen species and release of cytochrome c were regulated during this process. In addition, decreasing c-Myc level and increasing of phosphorylated p53 (Ser 15) and WAF1/p21 were also taken part in Mn-mediated lung toxicity. Proteasome inhibitor MG132 could increase c-Myc protein in abundance. Taking together, our results demonstrate that caspase-9-dependent intrinsic pathway, the downregulation of c-Myc and the upregulation of p53 and phosphorylated p53 might be responsible for Mn-mediated apoptosis in 16HBE cells. Moreover, c-Myc decrease might be due to increased degradation through the ubiquitin–proteasome pathway.