Journal Article Epublish 3 citations
PubMed: 35053120 DOI: 10.3390/biology11010123
Iron Inhibits the Translation and Activity of the Renal Epithelial Sodium Channel.
Biology (Basel) 11(1)
Authors: Abdel A Alli, Ling Yu, Ewa Wlazlo, Sadat Kasem, Mohammed F Gholam, Dhruv Desai, Carlos I Lugo, Sophie Vaulont, Yogesh M Scindia
Affiliations
- Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
- Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
- Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA 22904, USA.
- Department of Basic Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 21423, Saudi Arabia.
- Institut Cochin, Universite' de Paris, INSERM U1016, 75014 Paris, France.
- Division of Pulmonary Critical Care and Sleep Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
- Department of Pathology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Abstract
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.
MeSH
Hypertension, Hepcidins, Anemia, Cells, Epithelial Sodium Channels