H 2 O 2 signaling leads to the release of Nrf2 from complexes with Kelch-like ECH-associated protein 1 (Keap1) and ubiquitin ligase Cullin 3 and into the nucleus, where it binds to antioxidant response elements (ARE) and activates the expression of its target gene GPX8, which in turn regulates the expression of ER calcium by regulating SERCA ( 2 O 2 signaling and inhibiting Nrf2 translocation to the nucleus, resulting in a decrease in GPX8, resulting in increased ER calcium content and signaling ( via GPX8, in the same study, after silencing Nrf2 in HeLa cells, GPX8 mRNA and protein levels also decreased, resulting in elevated ER and cytosolic calcium levels at rest and increased histamine-induced ER calcium release ( FIGURE 7 In summary, the antioxidant stress of GPX8 is not only related to the oxidative folding of endoplasmic reticulum proteins, but also may play a vital role in regulating endoplasmic reticulum Ca 2+
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Clin Exp Allergy 35 : 12631271 Acknowledgements The Severe Asthma Research Program (SARP) is a multicenter asthma research group funded by the NHLBI and consisting of the following contributors (Principal Investigators are marked with an asterisk): Brigham & Women's HospitalElliot Israel*, Bruce D
doi: 10.3389/fmicb.2020.584812 122 ShiT.HouX.GuoS.ZhangL.WeiC.PengT.et al
