Characterisation of hepcidin response to holotransferrin treatment in CHO TRVb-1 cells
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Authors
Mehta, KoshaGreenwell, Pamela
Renshaw, Derek
Busbridge, Mark
Garcia, Mitla
Farnaud, Sébastien
Patel, Vinood B.
Affiliation
University of WestminsterCoventry University
Imperial College Healthcare NHS Trust
King's College London
University of Bedfordshire
Issue Date
2015-08-28Subjects
hepcidin
Metadata
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Iron overload coupled with low hepcidin levels are characteristics of hereditary haemochromatosis. To understand the role of transferrin receptor (TFR) and intracellular iron in hepcidin secretion, Chinese hamster ovary transferrin receptor variant (CHO TRVb-1) cells were used that express iron-response-element-depleted human TFRC mRNA (TFRC∆IRE). Results showed that CHO TRVb-1 cells expressed higher basal levels of cell-surface TFR1 than HepG2 cells (2.2-fold; p < 0.01) and following 5 g/L holotransferrin treatment maintained constitutive over-expression at 24h and 48 h, contrasting the HepG2 cells where the receptor levels significantly declined. Despite this, the intracellular iron content was neither higher than HepG2 cells nor increased over time under basal or holotransferrin-treated conditions. Interestingly, hepcidin secretion in CHO TRVb-1 cells exceeded basal levels at all time-points (p < 0.02) and matched levels in HepG2 cells following treatment. While TFRC mRNA expression showed expected elevation (2h, p < 0.03; 4h; p < 0.05), slc40a1 mRNA expression was also elevated (2 h, p < 0.05; 4 h, p < 0.03), unlike the HepG2 cells. In conclusion, the CHO TRVb-1 cells prevented cellular iron-overload by elevating slc40a1 expression, thereby highlighting its significance in the absence of iron-regulated TFRC mRNA. Furthermore, hepcidin response to holotransferrin treatment was similar to HepG2 cells and resembled the human physiological response.Citation
Mehta K, Greenwell P, Renshaw D, Busbridge M, Garcia M, Farnaud S, Patel VB (2015) 'Characterisation of hepcidin response to holotransferrin treatment in CHO TRVb-1 cells', Blood Cells, Molecules and Diseases, 55 (2), pp.110-8.Publisher
ElsevierPubMed ID
26142326Additional Links
https://www.sciencedirect.com/science/article/pii/S1079979615000807Type
ArticleLanguage
enISSN
1079-9796EISSN
1079-9796ae974a485f413a2113503eed53cd6c53
10.1016/j.bcmd.2015.05.002