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Proteasome inhibitors stimulate activator protein‐1 pathway via reactive oxygen species production
Author(s) -
Wu Hsiao-Mei,
Chi Kwan-Hwa,
Lin Wan-Wan
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03151-4
Subject(s) - lactacystin , proteasome , activator (genetics) , reactive oxygen species , mg132 , chemistry , glutathione , biochemistry , proteasome inhibitor , microbiology and biotechnology , biology , enzyme , gene
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)‐κB 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‐κB activation still transactivates IL‐8 gene expression.