Iron Inhibits the Translation and Activity of the Renal Epithelial Sodium Channel
2022
Alli, Abdel A. | Yu, Ling | Wlazlo, Ewa | Kasem, Sadat | Gholam, Mohammed F. | Desai, Dhruv | Lugo, Carlos I. | Vaulont, Sophie | Scindia, Yogesh M.
Hypertension is associated with an increased renal expression and activity of the epithelial sodium channel (ENaC) and iron deficiency. Distal tubules absorb iron, causing perturbations that may influence local responses. In this observational study, we investigated the relationship between iron content and ENaC expression and activity using two cell lines and hepcidin knockout mice (a murine model of iron overload). We found that iron did not transcriptionally regulate ENaC in hepcidin knockout mice or in vitro in collecting duct cells. However, the renal tubules of hepcidin knockout mice have a lower expression of ENaC protein. ENaC activity in cultured Xenopus 2F3 cells and mpkCCD cells was inhibited by iron, which could be reversed by iron chelation. Thus, our novel findings implicate iron as a regulator of ENaC protein and its activity.
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