Imperial College London
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DrAndrewCowburn

Faculty of Medicine, National Heart & Lung Institute

Senior Lecturer (Non-Clinical)
 
 
 
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a.cowburn

 
 
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Location

 

535ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Semba:2016:10.1038/ncomms11635,
author = {Semba, H and Takeda, N and Isagawa, T and Sugiura, Y and Honda, K and Wake, M and Miyazawa, H and Yamaguchi, Y and Miura, M and Jenkins, DMR and Choi, H and Kim, J-W and Asagiri, M and Cowburn, AS and Abe, H and Soma, K and Koyama, K and Katoh, M and Sayama, K and Goda, N and Johnson, RS and Manabe, I and Nagai, R and Komuro, I},
doi = {10.1038/ncomms11635},
journal = {Nature Communications},
pages = {1--10},
title = {HIF-1 alpha-PDK1 axis-induced active glycolysis plays an essential role in macrophage migratory capacity},
url = {http://dx.doi.org/10.1038/ncomms11635},
volume = {7},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - In severely hypoxic condition, HIF-1α-mediated induction of Pdk1 was found to regulate glucose oxidation by preventing the entry of pyruvate into the tricarboxylic cycle. Monocyte-derived macrophages, however, encounter a gradual decrease in oxygen availability during its migration process in inflammatory areas. Here we show that HIF-1α-PDK1-mediated metabolic changes occur in mild hypoxia, where mitochondrial cytochrome c oxidase activity is unimpaired, suggesting a mode of glycolytic reprogramming. In primary macrophages, PKM2, a glycolytic enzyme responsible for glycolytic ATP synthesis localizes in filopodia and lammelipodia, where ATP is rapidly consumed during actin remodelling processes. Remarkably, inhibition of glycolytic reprogramming with dichloroacetate significantly impairs macrophage migration in vitro and in vivo. Furthermore, inhibition of the macrophage HIF-1α-PDK1 axis suppresses systemic inflammation, suggesting a potential therapeutic approach for regulating inflammatory processes. Our findings thus demonstrate that adaptive responses in glucose metabolism contribute to macrophage migratory activity.
AU  - Semba,H
AU  - Takeda,N
AU  - Isagawa,T
AU  - Sugiura,Y
AU  - Honda,K
AU  - Wake,M
AU  - Miyazawa,H
AU  - Yamaguchi,Y
AU  - Miura,M
AU  - Jenkins,DMR
AU  - Choi,H
AU  - Kim,J-W
AU  - Asagiri,M
AU  - Cowburn,AS
AU  - Abe,H
AU  - Soma,K
AU  - Koyama,K
AU  - Katoh,M
AU  - Sayama,K
AU  - Goda,N
AU  - Johnson,RS
AU  - Manabe,I
AU  - Nagai,R
AU  - Komuro,I
DO  - 10.1038/ncomms11635
EP  - 10
PY  - 2016///
SN  - 2041-1723
SP  - 1
TI  - HIF-1 alpha-PDK1 axis-induced active glycolysis plays an essential role in macrophage migratory capacity
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/ncomms11635
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000376114500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/ncomms11635
UR  - http://hdl.handle.net/10044/1/85076
VL  - 7
ER  -
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