HFE mRNA expression is responsive to intracellular and extracellular iron loading

Mehta, K., Farnaud, S. and Patel, V.B. 2017. HFE mRNA expression is responsive to intracellular and extracellular iron loading. Molecular Biology Reports. 44 (5), pp. 399-403.

TitleHFE mRNA expression is responsive to intracellular and extracellular iron loading
AuthorsMehta, K., Farnaud, S. and Patel, V.B.
Abstract

Background: In liver hepatocytes, the HFE gene regulates cellular and systemic iron homeostasis by modulating cellular iron-uptake and producing the iron-hormone hepcidin in response to systemic iron elevation. However, the mechanism of iron-sensing in hepatocytes remain enigmatic. Therefore, to study the effect of iron on HFE and hepcidin (HAMP) expressions under distinct extracellular and intracellular iron-loading, we examined the effect of holotransferrin treatment (1,2, 5 and 8 g/L for 6 h) on intracellular iron levels, and mRNA expressions of HFE and HAMP in wild-type HepG2 and previously characterized iron-loaded recombinant-TfR1 HepG2 cells.

Methods and Results: Gene expression was analyzed by real-time PCR and intracellular iron was measured by ferrozine assay. Data showed that in the wild-type cells, where intracellular iron content remained unchanged, HFE expression remained unaltered at low holotransferrin treatments but was upregulated upon 5 g/L (p<0.04) and 8 g/L (p=0.05) treatments. HAMP expression showed alternating elevations and increased upon 1 g/L (p<0.05) and 5 g/L (p<0.05). However, in the recombinant cells that showed higher intracellular iron levels than wild-type cells, HFE and HAMP expressions were elevated only at low 1 g/L treatment (p<0.03) and were repressed at 2 g/L (p<0.03) treatment. Under holotransferrin-untreated conditions, the iron-loaded recombinant cells showed higher expressions of HFE (p<0.03) and HAMP (p=0.05) than wild-type cells.

Conclusions: HFE mRNA was independently elevated by extracellular and intracellular iron-excess. Thus, it may be involved in sensing both, extracellular and intracellular iron. Repression of HAMP expression under simultaneous intracellular and extracellular iron-loading resembles certain iron-excess pathologies.

KeywordsHFE, iron-sensing, holotransferrin, hepcidin
JournalMolecular Biology Reports
Journal citation44 (5), pp. 399-403
ISSN0301-4851
Year2017
PublisherSpringer
Publisher's version10.1007_s11033-017-4123-2.pdf
Digital Object Identifier (DOI)doi:10.1007/s11033-017-4123-2
Publication dates
Published24 Aug 2017
LicenseCC BY 4.0

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