Angiotensin II down-regulates transferrin receptor 1 and ferroportin 1 expression in Neuro-2a cells via activation of type-1 receptor

Angiotensin II (ANGII) modulates expression of iron intake and export proteins in cultured neurons. However, the relevant mechanisms have not been fully elucidated. Here, we investigated the effects of ANGII and/or candesartan, a ANGII-Type-1 Receptor (AT1R) antagonist, and PD123319, a ANGII-Type-2 Receptor (AT2R) antagonist on expression of transferrin receptor 1 (TfR1), ferroportin 1 (Fpn1)and ferritin as well as iron regulatory proteins (IRPs), hepcidin and nuclear factor E2-related factor 2 (Nrf2) in Neuro-2a cells. We demonstrated that ANGII induces a significant reduction in expression of TfR1, Fpn1, IRP2 proteins and Nrf2 mRNA and an increase in ferritin protein and hepcidin mRNA, while candesartan, but not PD123319, significantly attenuated or reversed all these ANGII-induced changes in Neuro-2a cells. These findings imply that ANGII down-regulates TfR1 expression likely via the AT1R/IRP2 pathway, and Fpn1 expression via ATR1/hepcidin and AT1R/ Nrf2 pathways.