Imperial College London
Alternate

ProfessorJaneMitchell

Faculty of Medicine, National Heart & Lung Institute

Professor of Pharmacology in Critical Care Medicine
 
 
 
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Contact

 

+44 (0)20 7351 8137j.a.mitchell

 
 
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Assistant

 

Ms Lisa Quinn +44 (0)20 7594 1345

 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tesfai:2017:10.1371/journal.pone.0183025,
author = {Tesfai, A and MacCallum, N and Kirkby, NS and Gashaw, H and Gray, N and Quinlan, G and Mumby, S and Leiper, JM and Paul-Clark, M and Ahmetaj-Shala, B and Mitchell, JA},
doi = {10.1371/journal.pone.0183025},
journal = {PLoS ONE},
title = {Metabolomic profiling of amines in sepsis predicts changes in NOS canonical pathways},
url = {http://dx.doi.org/10.1371/journal.pone.0183025},
volume = {12},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - RationaleNitric oxide synthase (NOS) is a biomarker/target in sepsis. NOS activity is driven by amino acids, which cycle to regulate the substrate L-arginine in parallel with cycles which regulate the endogenous inhibitors ADMA and L-NMMA. The relationship between amines and the consequence of plasma changes on iNOS activity in early sepsis is not known.ObjectiveOur objective was to apply a metabolomics approach to determine the influence of sepsis on a full array of amines and what consequence these changes may have on predicted iNOS activity.Methods and measurements34 amino acids were measured using ultra purification mass spectrometry in the plasma of septic patients (n = 38) taken at the time of diagnosis and 24–72 hours post diagnosis and of healthy volunteers (n = 21). L-arginine and methylarginines were measured using liquid-chromatography mass spectrometry and ELISA. A top down approach was also taken to examine the most changed metabolic pathways by Ingenuity Pathway Analysis. The iNOS supporting capacity of plasma was determined using a mouse macrophage cell-based bioassay.Main resultsOf all the amines measured 22, including L-arginine and ADMA, displayed significant differences in samples from patients with sepsis. The functional consequence of increased ADMA and decreased L-arginine in context of all cumulative metabolic changes in plasma resulted in reduced iNOS supporting activity associated with sepsis.ConclusionsIn early sepsis profound changes in amine levels were defined by dominant changes in the iNOS canonical pathway resulting in functionally meaningful changes in the ability of plasma to regulate iNOS activity ex vivo.
AU  - Tesfai,A
AU  - MacCallum,N
AU  - Kirkby,NS
AU  - Gashaw,H
AU  - Gray,N
AU  - Quinlan,G
AU  - Mumby,S
AU  - Leiper,JM
AU  - Paul-Clark,M
AU  - Ahmetaj-Shala,B
AU  - Mitchell,JA
DO  - 10.1371/journal.pone.0183025
PY  - 2017///
SN  - 1932-6203
TI  - Metabolomic profiling of amines in sepsis predicts changes in NOS canonical pathways
T2  - PLoS ONE
UR  - http://dx.doi.org/10.1371/journal.pone.0183025
UR  - http://hdl.handle.net/10044/1/50464
VL  - 12
ER  -
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