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Last Updated: Oct 11, 2012 - 10:22:56 PM
Biotechnology Channel

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Latest Research : Biotechnology

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Triterpenoids Protect Against Oxidative and Electrophile Stress

Mar 30, 2005 - 6:45:00 AM
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.

[RxPG] 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.

Publication: "Extremely potent triterpenoid inducers of the phase 2 response: Correlations of protection against oxidant and inflammatory stress" by Albena T. Dinkova-Kostova, Karen T. Liby, Katherine K. Stephenson, W. David Holtzclaw, Xiangqun Gao, Nanjoo Suh, Charlotte Williams, Renee Risingsong, Tadashi Honda, Gordon W. Gribble, Michael B. Sporn, and Paul Talalay
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Proceedings of the National Academy of Sciences of the United States of America

PNAS is one of the world's most-cited multidisciplinary scientific serials. Since its establishment in 1914, it continues to publish cutting-edge research reports, commentaries, reviews, perspectives, colloquium papers, and actions of the Academy. Coverage in PNAS spans the biological, physical, and social sciences. PNAS is published weekly in print, and daily online in PNAS Early Edition. The PNAS impact factor is 10.3 for 2003. PNAS is available by subscription.

PNAS is abstracted and/or indexed in: Index Medicus, PubMed Central, Current Contents, Medline, SPIN, JSTOR, ISI Web of Science, and BIOSIS.

Please note that the articles in PNAS report original research by independent authors and do not necessarily represent the views of the National Academy of Sciences or the National Research Council.
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