guanosine-diphosphate and Anemia--Iron-Deficiency

Hepcidin, a peptide hormone, is a key regulator in mammalian iron homeostasis. Increased level of hepcidin due to inflammatory conditions stimulates the ferroportin (FPN) transporter internalization, impairing the iron absorption; clinically manifested as anemia of inflammation (AI). Inhibiting hepcidin-mediated FPN degradation is proposed as an important strategy to combat AI. A systematic approach involving in silico, in vitro, ex vivo and in vivo studies is employed to identify hepcidin-binding agents. The virtual screening of 68,752 natural compounds via molecular docking resulted into identification of guanosine 5'-diphosphate (GDP) as a promising hepcidin-binding agent. The molecular dynamics simulations helped to identify the important hepcidin residues involved in stabilization of hepcidin-GDP complex. The results gave a preliminary indication that GDP may possibly inhibit the hepcidin-FPN interactions. The in vitro studies revealed that GDP caused FPN stabilization (FPN-GFP cell lines) and increased the FPN-mediated cellular iron efflux (HepG2 and Caco-2 cells). Interestingly, the co-administration of GDP and ferrous sulphate (FeSO

Topics: Anemia, Iron-Deficiency; Animals; Caco-2 Cells; Cation Transport Proteins; Disease Models, Animal; Guanosine Diphosphate; Hep G2 Cells; Hepcidins; Humans; Interleukin-6; Iron; Mice; Molecular Docking Simulation; Molecular Dynamics Simulation; Protein Binding; STAT3 Transcription Factor; Trace Elements; Treatment Outcome