Imperial College London

Professor Claire Shovlin

Faculty of MedicineNational Heart & Lung Institute

Professor of Practice (Clinical and Molecular Medicine)
 
 
 
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Contact

 

c.shovlin Website

 
 
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Location

 

534Block L Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mollet:2016:10.1371/journal.pone.0147990,
author = {Mollet, IG and Patel, D and Govani, FS and Giess, A and Paschalaki, K and Periyasamy, M and Lidington, EC and Mason, JC and Jones, MD and Game, L and Ali, S and Shovlin, CL},
doi = {10.1371/journal.pone.0147990},
journal = {PLOS One},
title = {Low Dose Iron Treatments Induce a DNA Damage Response in Human Endothelial Cells within Minutes},
url = {http://dx.doi.org/10.1371/journal.pone.0147990},
volume = {11},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - BackgroundSpontaneous reports from patients able to report vascular sequelae in real time, and recognitionthat serum non transferrin bound iron may reach or exceed 10μmol/L in the bloodstream after iron tablets or infusions, led us to hypothesize that conventional iron treatmentsmay provoke acute vascular injury. This prompted us to examine whether a phenotypecould be observed in normal human endothelial cells treated with low dose iron.MethodologyConfluent primary human endothelial cells (EC) were treated with filter-sterilized iron (II) citrateor fresh media for RNA sequencing and validation studies. RNA transcript profiles wereevaluated using directional RNA sequencing with no pre-specification of target sequences.Alignments were counted for exons and junctions of the gene strand only, blinded to treatmenttypes.Principal FindingsRapid changes in RNA transcript profiles were observed in endothelial cells treated with10μmol/L iron (II) citrate, compared to media-treated cells. Clustering for Gene Ontology(GO) performed on all differentially expressed genes revealed significant differences in biologicalprocess terms between iron and media-treated EC, whereas 10 sets of an equivalentnumber of randomly selected genes from the respective EC gene datasets showed no significantdifferences in any GO terms. After 1 hour, differentially expressed genes clusteredto vesicle mediated transport, protein catabolism, and cell cycle (Benjamini p = 0.0016,0.0024 and 0.0032 respectively), and by 6 hours, to cellular response to DNA damage stimulusmost significantly through DNA repair genes FANCG, BLM, and H2AFX. Comet assays demonstrated that 10μM iron treatment elicited DNA damage within 1 hour. This wasaccompanied by a brisk DNA damage response pulse, as ascertained by the developmentof DNA damage response (DDR) foci, and p53 stabilization.SignificanceThese data suggest that low dose iron treatments are sufficient to modify the vascular endothelium,and induce a DNA damage
AU - Mollet,IG
AU - Patel,D
AU - Govani,FS
AU - Giess,A
AU - Paschalaki,K
AU - Periyasamy,M
AU - Lidington,EC
AU - Mason,JC
AU - Jones,MD
AU - Game,L
AU - Ali,S
AU - Shovlin,CL
DO - 10.1371/journal.pone.0147990
PY - 2016///
SN - 1932-6203
TI - Low Dose Iron Treatments Induce a DNA Damage Response in Human Endothelial Cells within Minutes
T2 - PLOS One
UR - http://dx.doi.org/10.1371/journal.pone.0147990
UR - http://hdl.handle.net/10044/1/29463
VL - 11
ER -