Barr Johnny, Sharma Chidananda S, Sarkar Shubhashish, Wise Kimberly, Dong Liang, Periyakaruppan Adaikkappan, Ramesh Govindarajan T
Department of Biology, Molecular Neurotoxicology Laboratory/Proteomics Core, Texas Southern University, 3100 Cleburne St, Houston, TX 77004, USA.
Mol Cell Biochem. 2007 Mar;297(1-2):93-9. doi: 10.1007/s11010-006-9333-1. Epub 2006 Oct 5.
Cigarette smoke is a complex mixture of more than 4700 chemical compounds including free radicals and oxidants. Toxicity exhibited by cigarette smoke may be due to combined action of these compounds inducing many cellular processes mediated through reactive oxygen species (ROS). Major player probably nicotine as it is present in tobacco, in higher concentrations. The compounds that induce intracellular oxidative stress recognized as the important agents involved in the damage of biological molecules. Experiments using animal and cell culture model systems suggested that moderately higher concentrations of some forms of ROS like NO and H(2)O(2) can act as signal transducing agents. Nuclear transcription factor kappaB (NF-kappaB) an inducible transcription factor detected in neurons found to be involved in many biological processes such as inflammation, innate immunity, development, apoptosis, and antiapoptosis. Our present study demonstrates that nicotine induces ROS levels in a dose dependent manner in rat mesencephalic cells. Electro mobility shift analysis showed that nicotine activates inducible NF-kappaB by binding to consensus sequence of DNA. Nicotine added to cell culture stimulates the degradation of IkappaB-alpha subunit in 2 h. Further activation of c-Jun terminal kinase indicates that nicotine induces oxidative stress leading to activation of stress dependent NF-kappaB pathway in mesencephalic cells.
香烟烟雾是一种由4700多种化合物组成的复杂混合物，其中包括自由基和氧化剂。香烟烟雾所表现出的毒性可能是由于这些化合物的联合作用，诱导了许多通过活性氧（ROS）介导的细胞过程。主要成分可能是尼古丁，因为它在烟草中的含量较高。那些诱导细胞内氧化应激的化合物被认为是参与生物分子损伤的重要因素。使用动物和细胞培养模型系统进行的实验表明，某些形式的ROS（如NO和H₂O₂）浓度适度升高时可作为信号转导因子。核转录因子κB（NF-κB）是一种在神经元中检测到的可诱导转录因子，发现其参与许多生物过程，如炎症、先天免疫、发育、凋亡和抗凋亡。我们目前的研究表明，尼古丁在大鼠中脑细胞中以剂量依赖的方式诱导ROS水平升高。电泳迁移率变动分析表明，尼古丁通过与DNA共有序列结合来激活可诱导的NF-κB。添加到细胞培养物中的尼古丁在2小时内刺激IκB-α亚基的降解。c-Jun末端激酶的进一步激活表明，尼古丁诱导氧化应激，导致中脑细胞中应激依赖性NF-κB途径的激活。
