Imperial College London
Alternate

DrPrashantSrivastava

Faculty of Medicine, National Heart & Lung Institute

Lecturer in Cardiovascular Bioinformatics and Medical Statis
 
 
 
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Contact

 

prashant.srivastava

 
 
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Location

 

337ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Papathanassiu:2017:10.1038/ncomms16040,
author = {Papathanassiu, AE and Ko, JH and Imprialou, M and Bagnati, M and Srivastava, PK and Vu, HA and Cucchi, D and McAdoo, SP and Ananieva, EA and Mauro, C and Behmoaras, JV},
doi = {10.1038/ncomms16040},
journal = {Nature Communications},
title = {BCAT1 controls metabolic reprogramming in activated human macrophages and is associated with inflammatory diseases},
url = {http://dx.doi.org/10.1038/ncomms16040},
volume = {8},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Branched-chain aminotransferases (BCAT) are enzymes that initiate the catabolism of branched-chain amino acids (BCAA), such as leucine, thereby providing macromolecule precursors; however, the function of BCATs in macrophages is unknown. Here we show that BCAT1 is the predominant BCAT isoform in human primary macrophages. We identify ERG240 as a leucine analogue that blocks BCAT1 activity. Selective inhibition of BCAT1 activity results in decreased oxygen consumption and glycolysis. This decrease is associated with reduced IRG1 levels and itaconate synthesis, suggesting involvement of BCAA catabolism through the IRG1/itaconate axis within the tricarboxylic acid cycle in activated macrophages. ERG240 suppresses production of IRG1 and itaconate in mice and contributes to a less proinflammatory transcriptome signature. Oral administration of ERG240 reduces the severity of collagen-induced arthritis in mice and crescentic glomerulonephritis in rats, in part by decreasing macrophage infiltration. These results establish a regulatory role for BCAT1 in macrophage function with therapeutic implications for inflammatory conditions.
AU  - Papathanassiu,AE
AU  - Ko,JH
AU  - Imprialou,M
AU  - Bagnati,M
AU  - Srivastava,PK
AU  - Vu,HA
AU  - Cucchi,D
AU  - McAdoo,SP
AU  - Ananieva,EA
AU  - Mauro,C
AU  - Behmoaras,JV
DO  - 10.1038/ncomms16040
PY  - 2017///
SN  - 2041-1723
TI  - BCAT1 controls metabolic reprogramming in activated human macrophages and is associated with inflammatory diseases
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/ncomms16040
UR  - http://hdl.handle.net/10044/1/48704
VL  - 8
ER  -
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