Imperial College London
Alternate

DrIsabelGarcia Perez

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer in Precision and Systems Medicine
 
 
 
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Contact

 

i.garcia-perez

 
 
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Location

 

101Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Garcia-Perez:2012:10.1021/pr2012544,
author = {Garcia-Perez, I and Villaseñor, A and Wijeyesekera, A and Posma, JM and Stamler, J and Aronson, PS and Elliott, P and Unwin, R and Barbas, C and Nicholson, JK and Holmes, E},
doi = {10.1021/pr2012544},
journal = {Journal of Proteome Research},
pages = {4425--4435},
title = {Urinary metabolic phenotyping the slc26a6 (chloride-oxalate exchanger) null mouse model},
url = {http://dx.doi.org/10.1021/pr2012544},
volume = {11},
year = {2012}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The prevalence of renal stone disease is increasing, although it remains higher in men than in women when matched for age. While still somewhat controversial, several studies have reported an association between renal stone disease and hypertension, but this may be confounded by a shared link with obesity. However, independent of obesity, hyperoxaluria has been shown to be associated with hypertension in stone-formers and the most common type of renal stone is composed of calcium oxalate. The chloride-oxalate exchanger slc26a6 (also known as CFEX or PAT-1), located in the renal proximal tubule, was originally thought to have an important role in sodium homeostasis and thereby blood pressure control, but it has recently been shown to have a key function in oxalate balance by mediating oxalate secretion in the gut. We have applied two orthogonal analytical platforms (NMR spectroscopy and capillary-electrophoresis with UV detection) in parallel to characterize the urinary metabolic signatures related to the loss of the renal chloride-oxalate exchanger in slc26a6 null mice. Clear metabolic differentiation between the urinary profiles of the slc26a6 null and the wild type mice were observed using both methods, with the combination of NMR and CE-UV providing extensive coverage of the urinary metabolome. Key discriminating metabolites included oxalate, m-hydroxyphenylpropionylsulfate (m-HPPS), trimethylamine-N-oxide, glycolate and scyllo-inositol (higher in CFEX null mice) and hippurate, taurine, trimethylamine, and citrate (lower in slc26a6 null mice). In addition to the reduced efficiency of anion transport, several of these metabolites (hippurate, m-HPPS, methylamines) reflect alteration in gut microbial co-metabolic activities. Gender-related metabotypes were also observed in both wild type and slc26a6 null groups. Other urinary chemicals that showed a gender-specific pattern included trimethylamine, trimethylamine-N-oxide, citrate, spermidine, guanidinoacetate, and 2-
AU  - Garcia-Perez,I
AU  - Villaseñor,A
AU  - Wijeyesekera,A
AU  - Posma,JM
AU  - Stamler,J
AU  - Aronson,PS
AU  - Elliott,P
AU  - Unwin,R
AU  - Barbas,C
AU  - Nicholson,JK
AU  - Holmes,E
DO  - 10.1021/pr2012544
EP  - 4435
PY  - 2012///
SN  - 1535-3893
SP  - 4425
TI  - Urinary metabolic phenotyping the slc26a6 (chloride-oxalate exchanger) null mouse model
T2  - Journal of Proteome Research
UR  - http://dx.doi.org/10.1021/pr2012544
UR  - http://pubs.acs.org/doi/abs/10.1021/pr2012544
VL  - 11
ER  -
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