Nicotine induces oxidative stress and activates nuclear transcription factor kappa B in rat mesencephalic cells
Nicotine induces oxidative stress and activates nuclear transcription factor kappa B in rat mesencephalic cells
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DOI：
10.1007/s11010-006-9333-1
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发表时间：
2007-03-01
影响因子：
4.3
通讯作者：
Ramesh, Govindarajan T.
中科院分区：
文献类型：
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作者：
Barr, Johnny;Sharma, Chidananda S.;Ramesh, Govindarajan T.
香烟烟雾是 4700 多种化合物的复杂混合物，其中包括自由基和氧化剂。香烟烟雾表现出的毒性可能是由于这些化合物的联合作用，诱导了活性氧（ROS）介导的许多细胞过程。主要参与者可能是尼古丁，因为它存在于烟草中，浓度较高。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（例如 NO 和 H2O2）浓度稍高，可以充当信号转导剂。核转录因子 kappa B (NF-kappa B) 是一种在神经元中检测到的诱导转录因子，被发现参与许多生物过程，如炎症、先天免疫、发育、细胞凋亡和抗细胞凋亡。我们目前的研究表明，尼古丁以剂量依赖性方式诱导大鼠中脑细胞中的 ROS 水平。电迁移率变化分析表明，尼古丁通过与 DNA 共有序列结合来激活诱导型 NF-κ B。添加到细胞培养物中的尼古丁会在 2 小时内刺激 I kappa B-alpha 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-κ B 通路的激活。
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 H2O2 can act as signal transducing agents. Nuclear transcription factor kappa B (NF-kappa B) 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-kappa B by binding to consensus sequence of DNA. Nicotine added to cell culture stimulates the degradation of I kappa B-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-kappa B pathway in mesencephalic cells.