HFE mRNA expression is responsive to intracellular and extracellular iron loading: short communication
Mehta, K, Farnaud, S and Patel, VB (2017). HFE mRNA expression is responsive to intracellular and extracellular iron loading: short communication. Molecular Biology Reports. 44 (5), pp. 399-403.
|Authors||Mehta, K, Farnaud, S and Patel, VB|
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. 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 treatment (p < 0.03). 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. 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 non-hereditary iron-excess pathologies.
|Keywords||0601 Biochemistry And Cell Biology; Biochemistry & Molecular Biology|
|Journal||Molecular Biology Reports|
|Journal citation||44 (5), pp. 399-403|
|Digital Object Identifier (DOI)||doi:10.1007/s11033-017-4123-2|
|24 Aug 2017|
|Publication process dates|
|Deposited||02 Oct 2018|
|Accepted||19 Aug 2017|
|Accepted author manuscript|
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