Triterpenoids Protect Against Oxidative and Electrophile Stress
Mar 30, 2005 - 6:44:38 AM
Albena Dinkova-Kostova et al. report that synthetic triterpenoid (TP) analogs of oleanolic acid can activate the phase 2 response, which protects cells against electrophile and oxidant toxicities and blocks the inflammatory response to IFN-γ.
The specific mechanisms of the antiinflammatory and anticarcinogenic effects of these TPs remain unknown. To investigate these mechanisms, the authors exposed varying mouse and human cells to these TP analogs and detected an increase in the activity of NQO1, a chemoprotective enzyme, and a decrease in the synthesis of IFN-γ-evoked, proinflammatory iNOS and COX-2 enzymes.
Potencies of TP analogs for both responses closely correlated over a wide range of concentrations. The most effective analogs had activated Michael acceptor groups in rings A and C, at a critical distance from each other. In addition, TP-225, the most potent TP, protected human retinal epithelial cells against photooxidative damage by UV-A light.
Cells that lacked Nrf2, the principal phase 2 transcription factor, and/or Keap1, the sensor for inducers and a repressor of Nrf2, displayed diminished ability to respond to the TP analogs.
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