Nrf2 Activation by Oxidative Stress : (Cooperative Interaction of Nrf2 with Other Transactivators for Gene Regulation)

다국어 초록 (Multilingual Abstract)

Cellular signals are activated by the transducers attached to the cell surface plasma membrane in response to chemical modulators. Activation of antioxidant response element(ARE) by reactive oxygens produced by quinoid chemicals plays an important role in the regulation of phase Ⅱ antioxidant enzymes with the protein complex comprising Nrf proteins and Maf family members. In addition to Nrf2/ARE activation signal, the role of CCAAT/enhancer binding protein-(C/EBP)-mediated signaling pathway in the phase Ⅱ enzyme induction has been proved with the identification of the enhancer element(s) for the genes. Also, the PPARγ-RXR heterodimer promotes the PPAR-response enhancer module in the target gene and enhances Nrf2 and C/EBP activation. We also found that activation of the PPARγ-RXR plays a key role in anti oxidative gene induction via direct gene transactivation as well as coordinate induction of activating Nrf2 and C/EBP. The results in the present study provide implication that fatty acids and retinoids strongly affect the antioxidant gene regulation, whose transcription confers cancer chemoprevention as well as detoxification of xenobiotics and toxicants.