Biological functions of polyphenols-Search for their bindingfactors and mechanism in the binding

我们发现，多酚类物质，如双酚A（BPA）和白藜芦醇（RES）抑制细胞（Hep 3B细胞）的缺氧反应，BPA增强细胞（GH 3细胞）的T3-反应。然而，这些现象的机制仍然不清楚。我们已经发现BPA与蛋白质二硫键异构酶（PDI）结合并抑制其活性。在本研究中，我们发现PDI通过Ref-1调节T3受体的氧化还原状态，Ref-1最初被发现是缺氧反应的关键调节因子HIF-1α的氧化还原因子。这些结果表明，PDI调节细胞核因子的氧化还原状态，多酚可能通过抑制PDI而影响细胞核因子的活化。

We found that polyphenols such as bisphenol A (BPA) and resveratrol (RES) inhibited the hypoxic response of the cells (Hep3B cells) and that BPA enhanced the T3-response of the cells (GH3 cells). However, the mechanism of these phenomena was not still understood. We already found that BPA bounds to protein disulfide isomerase (PDI) and inhibits its activity. In this study, we found that PDI regulated the redox state of T3 receptor via Ref-1 which was originally found as redox factor of HIF-1α, the key regulator of hypoxic response. These findings suggest that PDI regulates the redox states of nucleus factors and poly phenol may affect the activation of nucleus factors by inhibition of PDI.