Banzet N, François D, Polla B S
Laboratory of Respiratory Physiology, UFR Cochin Port-Royal, Paris, France.
Redox Rep. 1999;4(5):229-36. doi: 10.1179/135100099101534945.
Smoking has been associated with a large number of diseases, in particular cancers. Among the many substances identified in tobacco smoke, reactive oxygen species (ROS) are major carcinogens. We have previously reported that exposure of mammalian cells to tobacco smoke induces the expression of stress proteins, as well as apoptosis (programmed cell death). Here we examined the effects of tobacco smoke on mitochondrial membrane potential (deltapsim), since mitochondria have been proposed to control the effector phase of apoptosis. We used normal human monocytes for these experiments, with the prospect for application of deltapsim as a biomarker of oxidative stress. Tobacco smoke induced mitochondrial depolarization at 3 h, and apoptosis (or necrosis for higher concentrations) after 16 h. Apoptosis was assessed by both a functional approach (annexin V binding) and morphological analysis (electron microscopy). N-acetyl-cysteine prevented tobacco smoke-induced deltapsim disruption and apoptosis, while the caspase inhibitor Z-VAD.Fmk did not affect deltapsim, though preventing apoptosis, and superoxide dismutase had no effect. Our data designate mitochondria as a target for ROS-mediated effects of tobacco smoke exposure.
吸烟与大量疾病相关，尤其是癌症。在烟草烟雾中鉴定出的众多物质中，活性氧（ROS）是主要致癌物。我们之前报道过，将哺乳动物细胞暴露于烟草烟雾中会诱导应激蛋白的表达以及细胞凋亡（程序性细胞死亡）。在此，我们研究了烟草烟雾对线粒体膜电位（Δψm）的影响，因为线粒体被认为可控制细胞凋亡的效应阶段。我们使用正常人单核细胞进行这些实验，期望将Δψm用作氧化应激的生物标志物。烟草烟雾在3小时时诱导线粒体去极化，16小时后诱导细胞凋亡（高浓度时为坏死）。通过功能方法（膜联蛋白V结合）和形态学分析（电子显微镜）评估细胞凋亡。N - 乙酰半胱氨酸可防止烟草烟雾诱导的Δψm破坏和细胞凋亡，而半胱天冬酶抑制剂Z - VAD.Fmk虽可防止细胞凋亡，但不影响Δψm，超氧化物歧化酶则无作用。我们的数据表明线粒体是烟草烟雾暴露的ROS介导效应的靶点。
