Taurine chloramine induces heme oxygenase-1 expression via Nrf2 activation in murine macrophages
Taurine chloramine induces heme oxygenase-1 expression via Nrf2 activation in murine macrophages
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DOI：
10.1016/j.intimp.2009.12.018
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发表时间：
2010-04-01
影响因子：
5.6
通讯作者：
Cha, Young-Nam
中科院分区：
文献类型：
--
作者：
Kim, Chaekyun;Jang, Jin Sun;Cha, Young-Nam
牛磺酸氯胺（TauCl）在活化的嗜中性粒细胞中通过储存的牛磺酸和髓过氧化物酶系统新产生的HOCl之间的反应大量产生，并且比HOC氧化性或毒性小得多。TauCl已显示通过抑制炎性介质的过度产生来提供针对炎性组织损伤的细胞保护。本研究的结果表明，TauCl上调RAW 264.7巨噬细胞中血红素加氧酶（HO）-1的表达并增加HO活性，而牛磺酸没有影响。TauCl本身在巨噬细胞中产生活性氧（ROS），并最初降低总谷胱甘肽（GSH）水平。TauCl增加NF-E2相关因子2（Nrf 2）的核转位，并增强其与抗氧化反应元件（ARE）的结合。这反过来又是HO-1表达上调的原因。总之，TauCl在RAW 264.7巨噬细胞中产生ROS并最初降低细胞GSH水平。Nrf 2与ARE结合后，HO-1表达增加，HO活性增强。因此，TauCl衍生的HO活性升高可能在炎症组织的适应性细胞保护中发挥重要作用。(C)2010 Elsevier B. V.保留所有权利。
Taurine chloramine (TauCl) is produced abundantly in activated neutrophils by a reaction between the stored taurine and the newly produced HOCl by the myeloperoxidase system, and is much less oxidizing or toxic than HOC. TauCl has been shown to provide cytoprotection against inflammatory tissue injury by inhibiting the overproduction of inflammatory mediators. The result of this study shows that TauCl upregulated the expression of heme oxygenase (HO)-1 and increased HO activity in RAW 264.7 macrophages, while taurine had no effect. TauCl by itself generated reactive oxygen species (ROS) in macrophages and diminished total glutathione (GSH) level initially. TauCl increased the nuclear translocation of NF-E2-related factor 2 (Nrf2) and enhanced its binding to the anti-oxidant response element (ARE). This, in turn, was responsible for the upregulation of HO-1 expression. In summary, TauCl generated ROS in RAW 264.7 macrophages and decreased cellular GSH level initially. This was responsible for the nuclear translocation of Nrf2 and its binding to ARE promoted the expression of HO-1 and increased HO activity. Thus, TauCl-derived elevation of HO activity may play an essential role in the adaptive cytoprotection of inflammatory tissues. (C) 2010 Elsevier B.V. All rights reserved.