[HTML][HTML] Proteasome inhibitors stimulate activator protein-1 pathway via reactive oxygen species production

HM Wu, KH Chi, WW Lin - FEBS letters, 2002 - Elsevier
HM Wu, KH Chi, WW Lin
FEBS letters, 2002Elsevier
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 …
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.
Elsevier