{"doi":"10.1016/j.redox.2021.102160","title":"Glutathione-S-transferase P promotes glycolysis in asthma in association with oxidation of pyruvate kinase M2","abstract":"BACKGROUND: Interleukin-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. METHODS: We 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. RESULTS: C-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. CONCLUSIONS: GSTP 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.","journal":"Redox Biology","year":2021,"id":158672,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9691,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":577787,"name":"Allison M. 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Adcock","orcid":"0000-0003-2101-8843","position":8,"is_corresponding":false},{"id":20850,"name":"Nazanin Zounemat Kermani","orcid":"0000-0003-2479-3861","position":9,"is_corresponding":false},{"id":668028,"name":"Florence Schleich","orcid":"0000-0002-2678-1373","position":10,"is_corresponding":false},{"id":668029,"name":"Renaud Louis","orcid":"0000-0002-4737-9084","position":11,"is_corresponding":false},{"id":356956,"name":"Eric Bohrnsen","orcid":"0000-0003-4327-5242","position":12,"is_corresponding":false},{"id":28360,"name":"Angelo D’Alessandro","orcid":"0000-0002-2258-6490","position":13,"is_corresponding":false},{"id":527308,"name":"Emiel F.�M. Wouters","orcid":"0000-0002-9186-575X","position":14,"is_corresponding":false},{"id":542618,"name":"Niki L. Reynaert","orcid":"0000-0002-8577-8094","position":15,"is_corresponding":false},{"id":268860,"name":"Jianing Li","orcid":"0000-0002-0143-8894","position":16,"is_corresponding":false},{"id":668030,"name":"C. Roland Wolf","orcid":"0000-0002-6969-0113","position":17,"is_corresponding":false},{"id":668031,"name":"Colin J. Henderson","orcid":"0000-0002-4764-639X","position":18,"is_corresponding":false},{"id":493384,"name":"Lennart K. A. Lundblad","orcid":"0000-0002-1749-8242","position":19,"is_corresponding":false},{"id":336717,"name":"Matthew E. Poynter","orcid":"0000-0002-7578-4570","position":20,"is_corresponding":false},{"id":668032,"name":"Anne E. Dixon","orcid":"0000-0002-7195-8270","position":21,"is_corresponding":false},{"id":420857,"name":"Charles G. 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