HFE mRNA expression is responsive to intracellular and extracellular iron loading: short communication

Mehta, K., Farnaud, S. and Patel, V.B. 2017. HFE mRNA expression is responsive to intracellular and extracellular iron loading: short communication. Molecular Biology Reports. 44 (5), pp. 399-403. https://doi.org/10.1007/s11033-017-4123-2

TitleHFE mRNA expression is responsive to intracellular and extracellular iron loading
AuthorsMehta, K.
Farnaud, S.
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 version
Digital Object Identifier (DOI)https://doi.org/10.1007/s11033-017-4123-2
Publication dates
Published24 Aug 2017
LicenseCC BY 4.0

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Gyamfi, D. and Patel, V. 2009. Liver metabolism: biochemical and molecular regulations. in: Preedy, V.R. (ed.) Nutrition, diet therapy, and the liver London CRC Press. pp. 3-15

Hepatic oxidative stress and apoptosis following acute alcohol
Everitt, H.E., Tewfik, I., Preedy, V.R. and Patel, V. 2009. Hepatic oxidative stress and apoptosis following acute alcohol. Alcohol & Alcoholism. 44, p. p85.

Identification of an iron-hepcidin complex
Farnaud, S., Rapisarda, C., Bui, T.T.T., Drake, A.F., Cammack, R. and Evans, R.W. 2008. Identification of an iron-hepcidin complex. Biochemical Journal. 413 (3), pp. 553-557. https://doi.org/10.1042/BJ20080406

Isolation of lactoferrin from milk of different species: calorimetric and antimicrobial studies
Conesa, C., Sánchez, L., Rota, C., Pérez, M.D., Calvo, M., Farnaud, S. and Evans, R.W. 2008. Isolation of lactoferrin from milk of different species: calorimetric and antimicrobial studies. Comparative Biochemistry and Physiology. Part B: Biochemistry & Molecular Biology. 150 (1), pp. 131-139. https://doi.org/10.1016/j.cbpb.2008.02.005

The interaction of arginine- and tryptophan-rich cyclic hexapeptides with Escherichia coli membranes
Junkes, C., Wessolowski, A., Farnaud, S., Evans, R.W., Good, L., Bienert, M. and Dathe, M. 2008. The interaction of arginine- and tryptophan-rich cyclic hexapeptides with Escherichia coli membranes. Journal of Peptide Science. 14 (4), pp. 535-543. https://doi.org/10.1002/psc.940

Tomatoes: origin, cultivation techniques, and germplasm resources
da Silva, D.J.H., Abreu, F.B., Caliman, F.R.B., Antonio, A.C. and Patel, V. 2008. Tomatoes: origin, cultivation techniques, and germplasm resources. in: Preedy, V.R. and Watson, R.R. (ed.) Tomatoes and tomato products: nutritional, medicinal and therapeutic properties CRC Press. pp. 3-26

Biochemical and spectroscopic studies of human melanotransferrin (MTf): electron-paramagnetic resonance evidence for a difference between the iron-binding site of MTf and other transferrins
Farnaud, S., Amini, M., Rapisarda, C., Cammack, R., Buic, T., Drake, A.F., Evans, R.W., Rahmanto, Y.S. and Richardson, D.R. 2008. Biochemical and spectroscopic studies of human melanotransferrin (MTf): electron-paramagnetic resonance evidence for a difference between the iron-binding site of MTf and other transferrins. International Journal of Biochemistry & Cell Biology. 40 (12), pp. 2739-2745. https://doi.org/10.1016/j.biocel.2008.07.003

Effects of 4-hydroxynonenal on mitochondrial 3-hydroxy-3methylglutaryl (HMG-CoA) synthase
Patel, V., Spencer, C.H., Young, T.A., Lively, M.O. and Cunningham, C.C. 2007. Effects of 4-hydroxynonenal on mitochondrial 3-hydroxy-3methylglutaryl (HMG-CoA) synthase. Free Radical Biology and Medicine. 43 (11), pp. 1499-1507. https://doi.org/10.1016/j.freeradbiomed.2007.08.004

Nutrition and alcoholic liver disease
Everitt, H.E., Patel, V. and Tewfik, I. 2007. Nutrition and alcoholic liver disease. Nutrition Bulletin. 32 (2), pp. 138-144. https://doi.org/10.1111/j.1467-3010.2007.00627.x

Characterisation of recombinant unglycosylated human serum transferrin purified from Saccharomyces cerevisiae
Sargent, P.J., Farnaud, S., Cammack, R., Zoller, H.M.P. and Evans, R.W. 2006. Characterisation of recombinant unglycosylated human serum transferrin purified from Saccharomyces cerevisiae. BioMetals. 19 (5), pp. 513-519. https://doi.org/10.1007/s10534-005-5532-6

Modelling of a metal-containing hepcidin
Farnaud, S., Patel, A. and Evans, R.W. 2006. Modelling of a metal-containing hepcidin. BioMetals. 19 (5), pp. 527-533. https://doi.org/10.1007/s10534-005-5883-z

An overview of molecular aspects of iron metabolism
Syed, B.A., Sargent, P.J., Farnaud, S. and Evans, R.W. 2006. An overview of molecular aspects of iron metabolism. Hemoglobin. 30 (1), pp. 69-80. https://doi.org/10.1080/03630260500455318

Towards a tree-induction approach to antimicrobial activity analysis of cationic peptides
Farnaud, S., Wang, Z., Dybowski, R., Odell, E.W. and Evans, R.W. 2006. Towards a tree-induction approach to antimicrobial activity analysis of cationic peptides. Biochemistry and Cell Biology. 84 (3), p. 394. https://doi.org/10.1139/O06-900

Structure/function overview of proteins involved in iron storage and transport
Sargent, P.J., Farnaud, S. and Evans, R.W. 2005. Structure/function overview of proteins involved in iron storage and transport. Current Medicinal Chemistry. 12 (23), pp. 2683-2693. https://doi.org/10.2174/092986705774462969

Protein adduct species in muscle and liver of rats following acute ethanol administration
Patel, V., Worrall, S., Emery, P.W. and Preedy, V.R. 2005. Protein adduct species in muscle and liver of rats following acute ethanol administration. Alcohol & Alcoholism. 40 (6), pp. 485-493. https://doi.org/10.1093/alcalc/agh196

Lactoferrin: the conductor of the immunological system?
Farnaud, S. and Evans, R.W. 2005. Lactoferrin: the conductor of the immunological system? in: Veskler, B.A. (ed.) New research on immunology New York Nova Science Publishers.

Variation in antimicrobial activity of lactoferricin-derived peptides explained by structure modelling
Farnaud, S., Patel, A., Odell, E.W. and Evans, R.W. 2004. Variation in antimicrobial activity of lactoferricin-derived peptides explained by structure modelling. FEMS Microbiology Letters. 238 (1), pp. 221-226. https://doi.org/10.1111/j.1574-6968.2004.tb09759.x

Liver dysfunction induced by bile duct ligation and galactosamine injection alters cardiac protein synthesis
Hunter, R.V., Patel, V., Baker, A.J. and Preedy, V.R. 2004. Liver dysfunction induced by bile duct ligation and galactosamine injection alters cardiac protein synthesis. Metabolism: Clinical and Experimental. 53 (8), pp. 964-968. https://doi.org/10.1016/j.metabol.2003.11.015

The plug domain of a neisserial TonB-dependent transporter retains structural integrity in the absence of its transmembrane β-barrel
Oke, M., Sarra, R., Ghirlando, R., Farnaud, S., Gorringe, A.R., Evans, R.W. and Buchanan, S.K. 2004. The plug domain of a neisserial TonB-dependent transporter retains structural integrity in the absence of its transmembrane β-barrel. FEBS Letters. 564 (3), pp. 294-300. https://doi.org/10.1016/S0014-5793(04)00196-6

Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity
Farnaud, S., Spiller, C., Moriarty, L.C., Patel, A., Gant, V., Odell, E.W. and Evans, R.W. 2004. Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity. FEMS Microbiology Letters. 233 (2/29), pp. 193-199. https://doi.org/10.1111/j.1574-6968.2004.tb09482.x

Lactoferrin: a multifunctional protein with antimicrobial properties
Farnaud, S. and Evans, R.W. 2003. Lactoferrin: a multifunctional protein with antimicrobial properties. Molecular Immunology. 40 (7), pp. 395-405. https://doi.org/10.1016/S0161-5890(03)00152-4

Protein metabolism in alcohol misuse and toxicity
Preedy, V.R., Koll, M., Adachi, J., Mantle, D., Patel, V. and Peters, T. 2003. Protein metabolism in alcohol misuse and toxicity. in: Watson, R.R. and Preedy, V.R. (ed.) Nutrition and alcohol: linking nutrient interactions and dietary intake London CRC Press. pp. 261-300

Chronic ethanol consumption increases the concentration of a 4-hydroxynonenal adduct with the mitochondrial hydroxy methyl glutaryl CoA synthase in liver
Patel, V., Spencer, C. and Cunningham, C.C. 2003. Chronic ethanol consumption increases the concentration of a 4-hydroxynonenal adduct with the mitochondrial hydroxy methyl glutaryl CoA synthase in liver. Hepatology. 38, p. p393.

Emerging techniques in biomedical research and their application to alcohol toxicity
Patel, V., Chaurand, P., Caprioli, R., Austen, B., Frears, E., Manca, F., Davies, H., Vrana, K., Wheeler, M. and Preedy, V.R. 2003. Emerging techniques in biomedical research and their application to alcohol toxicity. Alcoholism: Clinical and Experimental Research. 27 (2), pp. 348-353.

Support for a three-dimensional structure predicting a Cys-Glu-Lys catalytic triad for Pseudomonas aeruginosa amidase comes from site-directed mutagenesis and mutations altering substrate specificity
Novo, C., Farnaud, S., Tata, R., Clemente, A. and Brown, P.R. 2002. Support for a three-dimensional structure predicting a Cys-Glu-Lys catalytic triad for Pseudomonas aeruginosa amidase comes from site-directed mutagenesis and mutations altering substrate specificity. Biochemical Journal. 365 (3), pp. 731-738. https://doi.org/10.1042/BJ20011714

Altered hepatic mitochondrial ribosome structure following chronic ethanol consumption
Patel, V. and Cunningham, C.C. 2002. Altered hepatic mitochondrial ribosome structure following chronic ethanol consumption. Archives of Biochemistry and Biophysics. 398 (1), pp. 41-50. https://doi.org/10.1006/abbi.2001.2701

Chronic ethanol consumption increases the formation of an aldehyde-protein adduct in hepatic mitochondria
Patel, V., Young, T.A. and Cunningham, C.C. 2002. Chronic ethanol consumption increases the formation of an aldehyde-protein adduct in hepatic mitochondria. Alcoholism: Clinical and Experimental Research.

Cardioprotective effect of propranolol from alcohol-induced heart muscle damage as assessed by plasma cardiac troponin-T.
Patel, V., Ajmal, R., Sherwood, R., Sullivan, A., Richardson, P. and Preedy, V.R. 2001. Cardioprotective effect of propranolol from alcohol-induced heart muscle damage as assessed by plasma cardiac troponin-T. Alcoholism: Clinical and Experimental Research. 25 (6), pp. 882-889. https://doi.org/10.1111/j.1530-0277.2001.tb02294.x

Diarrhea reduces the rates of cardiac protein synthesis in myofibrillar protein fractions in rats in vivo
Hunter, R.V., Patel, V., Miell, J., Wong, H.J., Marway, J., Richardson, P. and Preedy, V.R. 2001. Diarrhea reduces the rates of cardiac protein synthesis in myofibrillar protein fractions in rats in vivo. Journal of Nutrition. 131 (5), pp. 1513-1519.

Acute doxorubicin (adriamycin) dosage does not reduce cardiac protein synthesis in vivo, but decreases diaminopeptidase I and proline endopeptidase activities
Zima, T., Tesar, V., Mantle, D., Koll, M., Patel, V., Richardson, P. and Preedy, V.R. 2001. Acute doxorubicin (adriamycin) dosage does not reduce cardiac protein synthesis in vivo, but decreases diaminopeptidase I and proline endopeptidase activities. Experimental and Molecular Pathology. 70 (2), pp. 154-161. https://doi.org/10.1006/exmp.2000.2353

Physiochemical properties of rat liver mitochondrial ribosomes
Patel, V., Cunningham, C.C. and Hantgan, R. 2001. Physiochemical properties of rat liver mitochondrial ribosomes. Journal of Biological Chemistry. 276 (9), pp. 6739-6746. https://doi.org/10.1074/jbc.M005781200

In vivo protein synthetic rates of atrial, ventricular, and pulmonary tissue proteins in aortic constriction, goldblatt, and bromoethylamine models of hypertension
Siddiq, T., Patel, V., Sherwood, R., Richardson, P. and Preedy, V.R. 2001. In vivo protein synthetic rates of atrial, ventricular, and pulmonary tissue proteins in aortic constriction, goldblatt, and bromoethylamine models of hypertension. Experimental and Molecular Pathology. 70 (1), pp. 19-30. https://doi.org/10.1006/exmp.2000.2333

Ethanol and oxidative stress
Sun, A., Ingelman-Sundberg, M., Neve, E., Matsumoto, H., Nishitani, Y., Minowa, Y., Fukui, Y., Bailey, S., Patel, V., Cunningham, C.C., Zima, T., Fialova, L., Mikulikova, L., Popov, P., Malbohan, I., Janebova, M., Nespor, K. and Sun, G. 2001. Ethanol and oxidative stress. Alcoholism: Clinical and Experimental Research. 25 (5 Suppl.), pp. 237S-243S.

Alpha-Tocopherol supplementation does not prevent acute alcohol-induced heart muscle damage
Koll, M., Patel, V., Sherwood, R.A., Seitz, H.K., Simanowski, U.A., Richardson, P.J., Peters, T.J. and Preedy, V.R. 2001. Alpha-Tocopherol supplementation does not prevent acute alcohol-induced heart muscle damage. Proceedings of the Nutrition Society. 60, p. P125A.

Ethanol and protein metabolism
Cunningham, C.C., Preedy, V.R., Paice, A., Hesketh, J., Peters, T., Patel, V., Volpi, E., Mawatari, K., Masaki, H., Mori, H. and Torii, K. 2001. Ethanol and protein metabolism. Alcoholism: Clinical and Experimental Research. 25 (5 Suppl.), pp. 262S-268S.

Chronic ethanol consumption alters the glutathione/glutathione peroxidase-1 system and protein oxidation status in rat liver
Bailey, S., Patel, V., Young, T.A., Asayama, K. and Cunningham, C.C. 2001. Chronic ethanol consumption alters the glutathione/glutathione peroxidase-1 system and protein oxidation status in rat liver. Alcoholism: Clinical and Experimental Research. 25 (5), pp. 726-733.

Evidence that cysteine-166 is the active-site nucleophile of Pseudomonas aeruginosa amidase: crystallization and preliminary X-ray diffraction analysis of the enzyme
Farnaud, S., Tata, R., Sohi, M.K., Wan, T., Brown, P.R. and Sutton, B.J. 1999. Evidence that cysteine-166 is the active-site nucleophile of Pseudomonas aeruginosa amidase: crystallization and preliminary X-ray diffraction analysis of the enzyme. Biochemical Journal. 340 (3), pp. 711-714.

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