Nicotinamide Mononucleotide Reduces Iron in BV-2 Cell by Up-Regulating Ferroportin 1 via Inhibiting the IL-6/STAT3/Hepcidin Pathway.

Abstract

Findings on the association of both nicotinamide mononucleotide (NMN) and iron metabolism with antiaging or aging led us to speculate that some pharmacological functions of NMN may be achieved partially by affecting iron metabolism. Here, we investigated the effects of NMN on cell viability, iron contents, oxidative stress, and the expression of ferritins, transferrin receptor 1 (TfR1), ferroportin1 (Fpn1), hepcidin, interleukin 6 (IL-6), interleukin-1β (IL-1β), and signal transducer and activator of transcription 3 (STAT3) in BV2 microglia (BV-2) cells treated with 150 μM of ferric ammonium citrate. We found that NMN induced a significant reduction in iron concentration, ferritin expression, and reactive oxygen species level, and an increase in cell viability in iron-overloaded BV-2 cells. Also, NMN significantly up-regulated TfR1 and down-regulated Fpn1 and hepcidin expression as well as IL-6, IL-1β, and pSTAT3 contents in iron-overloaded BV-2 cells. We concluded that NMN is able to regulate the expression of iron transport proteins TfR1 and Fpn1, via IL6/STAT3/hepcidin and IL-1β/hepcidin pathways, and then down-regulate iron contents and the expression of ferritin and inhibit oxidative stress in iron-overloaded BV-2 microglia cells, supporting that some pharmacological functions of NMN may be partly associated with the effects of NMN on iron metabolism. Our results suggest that NMN may have beneficial therapeutic effects on iron-related diseases such as neurodegenerative diseases.