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Characterisation of hepcidin response to holotransferrin treatment in CHO TRVb-1 cells

  • Kosha Mehta
    ,
  • Pamela Greenwell
    ,
  • Derek Renshaw
    ,
  • Mark Busbridge
    ,
  • Mitla Garcia
    ,
  • Sebastien Farnaud
  • University of Westminster
    ,
  • Coventry University
    ,
  • Imperial College Healthcare NHS Trust
    ,
  • King's College London
Research Output: Contribution to journal Article Peer-review

Abstract

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.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 110-8

Journal (Volume, Issue Number)

Blood Cells, Molecules, and Diseases (Volume 55, Issue 2)

Publication milestones

  • Published - 28/08/2015

Publication status

Published - 28/08/2015

ISSN

1079-9796

External Publication IDs

  • handle.net: 10547/623163
  • Scopus: 84933555881

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