A Measurement of the Calorimeter Response to Single Hadrons and Determination of the Jet Energy Scale Uncertainty Using LHC Run-1 PP-Collision Data with the ATLAS Detector

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dc.contributor.ORCIDhttp://dx.doi.org/10.1038/ncomms11635 (Kim, J-W)en_US
dc.contributor.authorSemba, H.en_US
dc.contributor.authorTakeda, N.en_US
dc.contributor.authorIsagawa, T.en_US
dc.contributor.authorSugiura, Y.en_US
dc.contributor.authorHonda, K.en_US
dc.contributor.authorWake, M.en_US
dc.contributor.authorMiyazawa, H.en_US
dc.contributor.authorJenkins, Dana M. R.en_US
dc.contributor.authorChoi, Hyunsungen_US
dc.contributor.authorKim, Jung-whanen_US
dc.contributor.utdAuthorJenkins, Dana M. R.en_US
dc.contributor.utdAuthorChoi, Hyunsungen_US
dc.contributor.utdAuthorKim, Jung-whanen_US
dc.date.accessioned2018-01-19T21:47:35Z
dc.date.available2018-01-19T21:47:35Z
dc.date.created2016-05-18
dc.date.issued2016-05-18en_US
dc.description.abstractIn 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.en_US
dc.description.sponsorshipen_US
dc.identifier.bibliographicCitationSemba, H., N. Takeda, T. Isagawa, Y. Sugiura, et al. 2016. "HIF-1α-PDK1 axis-induced active glycolysis plays an essential role in macrophage migratory capacity." Nature Communications 7, doi:10.1038/ncomms11635en_US
dc.identifier.issn2041-1723en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/5622
dc.identifier.volume7en_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.urihttp://dx.doi.org/10.1038/ncomms11635
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2016 The Authors. All Rights Reserved.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceNature Communications
dc.subjectCell migrationen_US
dc.subjectCell Movementen_US
dc.subjectSignal Transductionen_US
dc.subjectMetabolismen_US
dc.subjectMonocytesen_US
dc.subjectMacrophagesen_US
dc.titleA Measurement of the Calorimeter Response to Single Hadrons and Determination of the Jet Energy Scale Uncertainty Using LHC Run-1 PP-Collision Data with the ATLAS Detectoren_US
dc.type.genrearticleen_US

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