ABSTRACT
Glutathione peroxidase-1 (GPX1) is the first identified selenoprotein and selenoperoxidase in mammals. The down-regulation of regenerating islet-derived protein 2 (Reg2) expression in the GPX1-overproducing pancreatic islets was mediated by a transcriptional inhibition of the gene via two reactive oxygen species (ROS) responsive transcription factors: activator protein-1 and albumin D box-binding protein. Pancreatic and islet REG2 protein production and (or) secretion were positively correlated with the intracellular ROS status and inhibited by the ROS-scavengers or antioxidants. Chromatin immunoprecipitation of over-expressing (OE) and Wild-type (WT) islets and subsequential deletions of the binding sites in bTC-3 cells were performed to reveal the binding of transcriptional factors to the Reg2 promoter and the inhibition of the Reg2 promoter activation by ebselen using luciferase reporter assays. WT and OE mice were treated with ROS-generating diquat and streptozotocin for 48 h.
