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

2.50
Hdl Handle:
http://hdl.handle.net/10547/623163
Title:
Characterisation of hepcidin response to holotransferrin treatment in CHO TRVb-1 cells
Authors:
Mehta, Kosha ( 0000-0002-0716-5081 ) ; Greenwell, Pamela; Renshaw, Derek ( 0000-0002-2759-0229 ) ; Busbridge, Mark ( 0000-0002-5452-6986 ) ; Garcia, Mitla; Farnaud, Sébastien ( 0000-0003-2077-5797 ) ; Patel, Vinood B.
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.
Affiliation:
University of Westminster; Coventry University; Imperial College Healthcare NHS Trust; King's College London; University of Bedfordshire
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:
Elsevier
Journal:
Blood Cells, Molecules and Diseases
Issue Date:
28-Aug-2015
URI:
http://hdl.handle.net/10547/623163
DOI:
10.1016/j.bcmd.2015.05.002
PubMed ID:
26142326
Additional Links:
https://www.sciencedirect.com/science/article/pii/S1079979615000807
Type:
Article
Language:
en
ISSN:
1079-9796
EISSN:
1079-9796
Appears in Collections:
Biomedical and biological science

Full metadata record

DC FieldValue Language
dc.contributor.authorMehta, Koshaen
dc.contributor.authorGreenwell, Pamelaen
dc.contributor.authorRenshaw, Dereken
dc.contributor.authorBusbridge, Marken
dc.contributor.authorGarcia, Mitlaen
dc.contributor.authorFarnaud, Sébastienen
dc.contributor.authorPatel, Vinood B.en
dc.date.accessioned2019-02-15T13:32:11Z-
dc.date.available2019-02-15T13:32:11Z-
dc.date.issued2015-08-28-
dc.identifier.citationMehta 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.en
dc.identifier.issn1079-9796-
dc.identifier.pmid26142326-
dc.identifier.doi10.1016/j.bcmd.2015.05.002-
dc.identifier.urihttp://hdl.handle.net/10547/623163-
dc.description.abstractIron 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.en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttps://www.sciencedirect.com/science/article/pii/S1079979615000807en
dc.rightsGreen - can archive pre-print and post-print or publisher's version/PDF-
dc.subjecthepcidinen
dc.titleCharacterisation of hepcidin response to holotransferrin treatment in CHO TRVb-1 cellsen
dc.typeArticleen
dc.identifier.eissn1079-9796-
dc.contributor.departmentUniversity of Westminsteren
dc.contributor.departmentCoventry Universityen
dc.contributor.departmentImperial College Healthcare NHS Trusten
dc.contributor.departmentKing's College Londonen
dc.contributor.departmentUniversity of Bedfordshireen
dc.identifier.journalBlood Cells, Molecules and Diseasesen
dc.date.updated2019-02-15T13:28:41Z-
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