2,3,7,8-Tetrachlorodibenzo-p-dioxin impairs iron homeostasis by modulating iron-related proteins expression and increasing the labile iron pool in mammalian cells

摘要: Cellular iron metabolism is essentially controlled by the binding of cytosolic regulatory proteins (IRP1 or IRP2) to iron-responsive elements (IREs) located on mRNAs coding for involved in acquisition, utilization and storage. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) one most potent toxins current interest that occurs as poisonous chemical environment. TCDD exposure has been reported induce a broad spectrum toxic biological responses, including significant changes gene expression heme associated with liver injury. Here, we have investigated molecular effects providing first evidence administration toxin mammalian cells affects maintenance homeostasis. We found Madin-Darby Bovine Kidney cell caused divergent modulation IRP1 IRP2 RNA-binding capacity. Interestingly, observed concomitant down-regulation up-regulation thus determining marked enhancement transferrin receptor 1 (TfR-1) biphasic response ferritin content. changed content coupled TfR-1 induction after impairs cellular homeostasis, ultimately leading labile pool (LIP) extent. Since important requirement occur during regulation growth, it not surprising dioxin-dependent dysregulation herein described may be linked cell-fate decision, supporting hypothesis central connection among dioxins critical processes. This article part Special Issue entitled: 11th European Symposium Calcium.