Inflammation and ER Stress Downregulate BDH2 Expression and Dysregulate Intracellular Iron in Macrophages

Figure 10

A schematic presentation of proposed small molecule iron chelator acting similar to the mammalian siderophore 2,5-dihydroxybenzoic acid. The DFP-iron complex shares structural resemblance to enterobactin, the major bacterial siderophore that binds iron with very high affinity. As a defense mechanism, the host upregulates NGAL expression to scavenge enterobactin which in turn limits iron availability and inhibits bacterial growth. DFP is an iron chelating small molecule drug that gains access to cells and scavenges free intracellular iron and then exits as a DFP-iron complex. Based on the structural resemblance to enterobactin-iron complexes, the DFP-iron complex is expected to bind NGAL by fitting into the hydrophobic pocket [79]. Therefore, small molecule iron chelators may act as the mammalian siderophore and redistribute iron retained in macrophages.