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

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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.