Bisphenol A stabilizes Nrf2 via Ca<sup>2+</sup> influx by direct activation of the IP<sub>3</sub> receptor

Bisphenol A (BPA) is an endocrine-disrupting chemical used in polycarbonate and epoxy resins. Previously, we found that BPA stabilized the protein levels of nuclear factor erythroid 2-related 2 (Nrf2) by inducing Ca2+ efflux into cytosol, followed nitric oxide synthase activation, resulting enhanced nitrosylation Keap1, which a negative regulator Nrf2. However, mechanisms behind stimulation remain unknown. In present study, stimulated cytosol from ER, but not outside cells through plasma membrane Hep3B cells. Nrf2 stabilization were inhibited inhibitor inositol 1,4,5-trisphosphate (IP3) receptor, 2-aminoethoxydiphenylborane, endoplasmic reticulum. IP3 produced activation phospholipase C (PLC) lipid, phosphatidylinositol 4,5-bisphosphate (PIP2). The induction was PLC inhibitor, U-73122, suggesting does induce production via activation. We bound directly to binding core domain competed with on this site. addition, overexpression receptor BPA. These results clarified new target BPA, induces reticulum receptor.