Imperial College London

Professor Paul M. Matthews

Faculty of MedicineDepartment of Brain Sciences

Edmond and Lily Safra Chair. Head of Department
 
 
 
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Contact

 

+44 (0)20 7594 2855p.matthews

 
 
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Assistant

 

Ms Siobhan Dillon +44 (0)20 7594 2855

 
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Location

 

E502Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Owen:2017:10.1042/BCJ20170648,
author = {Owen, DRJ and Fan, J and Campioli, E and Venugopal, S and Midzak, A and Daly, E and Harlay, A and Issop, L and Libri, V and Kalogiannopoulou, D and Oliver, E and Gallego-Colon, E and Colasanti, A and Huson, L and Rabiner, EA and Suppiah, P and Essagian, C and Matthews, PM and Papadopoulos, V},
doi = {10.1042/BCJ20170648},
journal = {Biochemical Journal},
pages = {3985--3999},
title = {TSPO mutations in rats and a human polymorphism impair the rate of steroid synthesis},
url = {http://dx.doi.org/10.1042/BCJ20170648},
volume = {474},
year = {2017}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The 18kDa translocator protein (TSPO) is a ubiquitous conserved outer mitochondrial membrane protein implicated in numerous cell and tissue functions, including steroid hormone biosynthesis, respiration, cell proliferation, and apoptosis. TSPO binds with high affinity to cholesterol and numerous compounds, is expressed at high levels in steroid-synthesizing tissues, and mediates cholesterol import into mitochondria, which is the rate-limiting step in steroid formation. In humans, the rs6971 polymorphism on the TSPO gene leads to an amino acid substitution in the fifth transmembrane loop of the protein, which is where the cholesterol-binding domain of TSPO is located, and this polymorphism has been associated with anxiety-related disorders. However, recent knockout mouse models have provided inconsistent conclusions of whether TSPO is directly involved in steroid synthesis. In this report, we show that TSPO deletion mutations in rat and its corresponding rs6971 polymorphism in humans alter adrenocorticotropic hormone-induced plasma corticosteroid concentrations. Rat tissues examined show increased cholesteryl ester accumulation, and neurosteroid formation was undetectable in homozygous rats. These results also support a role for TSPO ligands in diseases with steroid-dependent stress and anxiety elements.
AU - Owen,DRJ
AU - Fan,J
AU - Campioli,E
AU - Venugopal,S
AU - Midzak,A
AU - Daly,E
AU - Harlay,A
AU - Issop,L
AU - Libri,V
AU - Kalogiannopoulou,D
AU - Oliver,E
AU - Gallego-Colon,E
AU - Colasanti,A
AU - Huson,L
AU - Rabiner,EA
AU - Suppiah,P
AU - Essagian,C
AU - Matthews,PM
AU - Papadopoulos,V
DO - 10.1042/BCJ20170648
EP - 3999
PY - 2017///
SN - 1470-8728
SP - 3985
TI - TSPO mutations in rats and a human polymorphism impair the rate of steroid synthesis
T2 - Biochemical Journal
UR - http://dx.doi.org/10.1042/BCJ20170648
UR - http://hdl.handle.net/10044/1/52491
VL - 474
ER -