The Role of Copper in the Regulation of Ferroportin Expression in Macrophages.
The critical function of ferroportin (Fpn) in maintaining iron homeostasis requires complex and multilevel control of its expression. Besides iron-dependent cellular and systemic control of Fpn expression, other metals also seem to be involved in regulating the Fpn gene. Here, we found that copper loading significantly enhanced Fpn transcription in an Nrf2-dependent manner in primary bone-marrow-derived macrophages (BMDMs). However, prolonged copper loading resulted in decreased Fpn protein abundance. Moreover, CuCl2 treatment induced Fpn expression in RAW 264.7 macrophages at both the mRNA and protein level. These data suggest that cell-type-specific regulations have an impact on Fpn protein stability after copper loading. Transcriptional suppression of Fpn after lipopolysaccharide (LPS) treatment contributes to increased iron storage inside macrophages and may result in anemia of inflammation. Here, we observed that in both primary BMDMs and RAW 264.7 macrophages, LPS treatment significantly decreased Fpn mRNA levels, but concomitant CuCl2 stimulation counteracted the transcriptional suppression of Fpn and restored its expression to the control level. Overall, we show that copper loading significantly enhances Fpn transcription in macrophages, while Fpn protein abundance in response to CuCl2 treatment, depending on macrophage type and factors specific to the macrophage population, can influence Fpn regulation in response to copper loading.
['Jończy|Aneta|A|0000-0002-4333-6853', 'Mazgaj|Rafał|R|0000-0001-6706-0882', 'Smuda|Ewa|E|', 'Żelazowska|Beata|B|', 'Kopeć|Zuzanna|Z|0000-0001-5869-7670', 'Starzyński|Rafał Radosław|RR|', 'Lipiński|Paweł|P|']
D000818:Animals D027682:Cation Transport Proteins D003300:Copper D005786:Gene Expression Regulation D006706:Homeostasis D007501:Iron D008070:Lipopolysaccharides D008264:Macrophages D051379:Mice
copper ferroportin macrophages LPS Nrf2