Imperial College London
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ProfessorIanAdcock

Faculty of Medicine, National Heart & Lung Institute

Professor of Respiratory Cell & Molecular Biology
 
 
 
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Contact

 

+44 (0)20 7594 7840ian.adcock Website

 
 
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Location

 

304Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{van:2021:10.1016/j.redox.2021.102160,
author = {van, de Wetering C and Manuel, AM and Sharafi, M and Aboushousha, R and Qian, X and Erickson, C and MacPherson, M and Chan, G and Adcock, IM and ZounematKermani, N and Schleich, F and Louis, R and Bohrnsen, E and D'Alessandro, A and Wouters, EF and Reynaert, NL and Li, J and Wolf, CR and Henderson, CJ and Lundblad, LKA and Poynter, ME and Dixon, AE and Irvin, CG and van, der Vliet A and van, der Velden JL and Janssen-Heininger, YM},
doi = {10.1016/j.redox.2021.102160},
journal = {Redox Biology},
pages = {1--11},
title = {Glutathione-S-transferase P promotes glycolysis in asthma in association with oxidation of pyruvate kinase M2},
url = {http://dx.doi.org/10.1016/j.redox.2021.102160},
volume = {47},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundInterleukin-1-dependent increases in glycolysis promote allergic airways disease in mice and disruption of pyruvate kinase M2 (PKM2) activity is critical herein. Glutathione-S-transferase P (GSTP) has been implicated in asthma pathogenesis and regulates the oxidation state of proteins via S-glutathionylation. We addressed whether GSTP-dependent S-glutathionylation promotes allergic airways disease by promoting glycolytic reprogramming and whether it involves the disruption of PKM2.MethodsWe used house dust mite (HDM) or interleukin-1β in C57BL6/NJ WT or mice that lack GSTP. Airway basal cells were stimulated with interleukin-1β and the selective GSTP inhibitor, TLK199. GSTP and PKM2 were evaluated in sputum samples of asthmatics and healthy controls and incorporated analysis of the U-BIOPRED severe asthma cohort database.ResultsAblation of Gstp decreased total S-glutathionylation and attenuated HDM-induced allergic airways disease and interleukin-1β-mediated inflammation. Gstp deletion or inhibition by TLK199 decreased the interleukin-1β-stimulated secretion of pro-inflammatory mediators and lactate by epithelial cells. 13C-glucose metabolomics showed decreased glycolysis flux at the pyruvate kinase step in response to TLK199. GSTP and PKM2 levels were increased in BAL of HDM-exposed mice as well as in sputum of asthmatics compared to controls. Sputum proteomics and transcriptomics revealed strong correlations between GSTP, PKM2, and the glycolysis pathway in asthma.ConclusionsGSTP contributes to the pathogenesis of allergic airways disease in association with enhanced glycolysis and oxidative disruption of PKM2. Our findings also suggest a PKM2-GSTP-glycolysis signature in asthma that is associated with severe disease.
AU  - van,de Wetering C
AU  - Manuel,AM
AU  - Sharafi,M
AU  - Aboushousha,R
AU  - Qian,X
AU  - Erickson,C
AU  - MacPherson,M
AU  - Chan,G
AU  - Adcock,IM
AU  - ZounematKermani,N
AU  - Schleich,F
AU  - Louis,R
AU  - Bohrnsen,E
AU  - D'Alessandro,A
AU  - Wouters,EF
AU  - Reynaert,NL
AU  - Li,J
AU  - Wolf,CR
AU  - Henderson,CJ
AU  - Lundblad,LKA
AU  - Poynter,ME
AU  - Dixon,AE
AU  - Irvin,CG
AU  - van,der Vliet A
AU  - van,der Velden JL
AU  - Janssen-Heininger,YM
DO  - 10.1016/j.redox.2021.102160
EP  - 11
PY  - 2021///
SN  - 2213-2317
SP  - 1
TI  - Glutathione-S-transferase P promotes glycolysis in asthma in association with oxidation of pyruvate kinase M2
T2  - Redox Biology
UR  - http://dx.doi.org/10.1016/j.redox.2021.102160
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000708436800005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.sciencedirect.com/science/article/pii/S2213231721003207?via%3Dihub
UR  - http://hdl.handle.net/10044/1/92572
VL  - 47
ER  -
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