Proteasome inhibitors stimulate activator protein-1 pathway via reactive oxygen species production
Proteasome inhibitors stimulate activator protein-1 pathway via reactive oxygen species production
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DOI：
10.1016/s0014-5793(02)03151-4
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发表时间：
2002-08-28
期刊：
影响因子：
3.5
通讯作者：
Lin, WW
中科院分区：
文献类型：
--
作者：
Wu, HM;Chi, KH;Lin, WW
本报告探讨了蛋白酶体抑制剂(MG132、aLLN、lactacystin和MG262)对白细胞介素8(IL-8)诱导的影响。在HEK293细胞中，蛋白酶体抑制剂可浓度依赖性地增强IL-8启动子和激活蛋白-1(AP-1)的活性，但抑制细胞因子诱导的核因子-kappaB的激活。N-乙酰半胱氨酸、谷胱甘肽、二苯碘、鱼藤酮和抗霉素A可降低对IL-8启动子和AP-1的刺激作用，2‘，7’-二氯二氢荧光素二乙酸酯的荧光分析进一步证实了蛋白酶体抑制剂诱导ROS产生的能力。这些结果表明，蛋白酶体抑制剂产生ROS导致AP-1激活，而AP-1在没有NF-kappaB激活的情况下仍能反式激活IL-8基因的表达。(C)2002年欧洲生化学会联合会。爱思唯尔科学公司出版。版权所有。
In this report we explored the effects of proteasome inhibitors (MG132, aLLN, lactacystin and MG262) on interleukin-8 (IL-8) induction. In HEK293 cells, proteasome inhibitors could concentration-dependently increase IL-8 promoter and activator protein-1 (AP-1) activities, but inhibited nuclear factor (NF)-kappaB activation induced by cytokines. The stimulating effects on IL-8 promoter and AP-1 were reduced by N-acetylcysteine, glutathione, diphenyleneiodonium, rotenone and antimycin A. Fluorescent analysis using 2',7'-dichlorodihydrofluorescin diacetate further confirmed the abilities of proteasome inhibitors to induce reactive oxygen species (ROS) production. These results suggest that ROS production by proteasome inhibitors leads to AP-1 activation, which in the absence of NF-kappaB activation still transactivates IL-8 gene expression. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.