The role of hydroxyl radical as a messenger in the activation of nuclear transcription factor NF-κB
The role of hydroxyl radical as a messenger in the activation of nuclear transcription factor NF-κB
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羟基自由基作为信使在核转录因子NF-κB激活中的作用
DOI：
10.1023/a:1006904904514
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发表时间：
1999
影响因子：
4.3
通讯作者：
V. Vallyathan
中科院分区：
文献类型：
--
作者：
Xianglin Shi;Z. Dong;Chuanshu Huang;W. Ma;K. Liu;Fei Chen;S. Leonard;M. Ding;V. Castranova;V. Vallyathan
虽然一般认为活性氧类激活NF-κB，一种主要的氧化应激反应性转录因子，但尚不清楚这些物质中哪一种引起NF-κB激活。我们的假设是羟基自由基（·OH）作为一种信使参与NF-κB的活化。使用Jurkat细胞、巨噬细胞和JB 6细胞来检验这一假设。Cr（VI）、SiO2和ZnO被用作·OH自由基的来源。这些·OH生成系统均不涉及外源性H2 O2。Cr（VI）诱导Jurkat细胞NF-κB活性增强。金属螯合剂二乙烯三胺五乙酸或过氧化氢清除剂过氧化氢酶可降低NF-κB的活化，但超氧化物歧化酶可增加NF-κB的活化。Mn（II）与Cr（IV）反应抑制金属离子介导的·OH生成，降低NF-κB活化。OH自由基清除剂甲酸钠也能抑制NF-κB的活化。电子自旋共振测量显示Cr（VI）被Jurket细胞还原为Cr（IV）和Cr（V）。在还原过程中，分子氧先被还原为O2-，再被还原为H2 O2，H2 O2与Cr（IV）和Cr（V）反应生成·OH自由基。·OH的产生与Cr（VI）诱导的NF-κB活化有关。同样，二氧化硅通过·OH自由基介导的反应引起巨噬细胞中的NF-κB活化。这种自由基是通过金属介导的H2 O2反应产生的，H2 O2是通过氧化硅刺激的“可呼吸爆发”期间的中间体O2-还原分子氧而产生的。二氧化硅颗粒在Jurket或JB 6细胞中均未引起·OH产生，因此在这些细胞中未引起任何可观察到的NF-κB活化。电子自旋共振（ESR）检测结果表明，ZnO通过光照射产生的·OH诱导JB 6细胞NF-κB活化。因此，结果表明·OH自由基作为NF-κB活化的信使发挥作用。清除·OH自由基或其前体的抗氧化剂抑制NF-κB的活化。金属螯合剂使金属离子不能从H2 O2生成·OH，从而抑制该转录因子的活化。
Although it is generally believed that reactive oxygen species activate NF-κB, a primary oxidative stress-responsive transcription factor, it is unclear which one among these species causes NF-κB activation. Our hypothesis is that hydroxyl radical (·OH) functions as a messenger for the activation of NF-κB. Jurkat cells, macrophages and JB6 cells were used to test this hypothesis. Cr(VI), silica and ZnO were used as sources of ·OH radicals. None of these ·OH generating systems involves exogenous H2O2. Cr(VI) expressed enhanced activity in induction of NF-κB in Jurkat cells. This activation of NF-κB was decreased by a metal chelator, diethylene triaminepentaacetic acid or a H2O2 scavenger, catalase, but was increased by superoxide dismutase. Mn(II), which reacts with Cr(IV) to inhibit this metal ion-mediated ·OH generation, decreased the NF-κB activation. Sodium formate, an ·OH radical scavenger, also inhibited the NF-κB activation. Electron spin resonance measurements show that Cr(VI) was reduced by Jurket cells to Cr(IV) and Cr(V). During the reduction process, molecular oxygen was reduced to O2- and then to H2O2, which reacted with Cr(IV) and Cr(V) to generate ·OH radical. The ·OH generation correlated with the Cr(VI)-induced NF-κB activation. Similarly, silica caused NF-κB activation in macrophages via the ·OH radical-mediated reaction. This radical was generated via metal mediated reaction from H2O2, which was generated by the reduction of molecular oxygen via O2- as an intermediate during the silica-stimulated ‘respirable burst’. Silica particles did not cause ·OH generation either in Jurket or in JB6 cells and thus did not cause any observable NF-κB activation in these cells. ZnO induced NF-κB activation in JB6 cells through the generation of ·OH resulting from light irradiation of ZnO which was measured by electron spin resonance. The results thus show that ·OH radical functions as a messenger for NF-κB activation. Antioxidants, which scavenge ·OH radical or its precursors, inhibit NF-κB activation. Metal chelators, which make metal ions incapable of generating ·OH from H2O2, inhibit activation of this transcription factor.
DOI：
10.1073/pnas.91.24.11527
发表时间：
1994-11-22
影响因子：
11.1
作者：
ANDERSON, MT;STAAL, FJT;HERZENBERG, LA
通讯作者：
HERZENBERG, LA