Pyruvate kinase M2 and the mitochondrial ATPase Inhibitory Factor 1 provide novel biomarkers of dermatomyositis: a metabolic link to oncogenesis.

Background Metabolic alterations play a role in the development of inflammatory myopathies (IMs). Herein, we have investigated through a multiplex assay whether proteins of energy metabolism could provide biomarkers of IMs. Methods A cohort of thirty-two muscle biopsies and forty plasma samples comp...

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Autores: Santacatterina, Fulvio, Sánchez Aragó, María, Catalán García, Marc, Garrabou Tornos, Glòria, Nuñez de Arenas, Cristina, Grau Junyent, Josep M. (Josep Maria), Cardellach, Francesc, Cuezva, José M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/109650
Acceso en línea:https://hdl.handle.net/2445/109650
Access Level:acceso abierto
Palabra clave:Marcadors bioquímics
Dermatomiositis
Miositis
Malalties musculars
Biochemical markers
Dermatomyositis
Myositis
Muscular Diseases
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spelling Pyruvate kinase M2 and the mitochondrial ATPase Inhibitory Factor 1 provide novel biomarkers of dermatomyositis: a metabolic link to oncogenesis.Santacatterina, FulvioSánchez Aragó, MaríaCatalán García, MarcGarrabou Tornos, GlòriaNuñez de Arenas, CristinaGrau Junyent, Josep M. (Josep Maria)Cardellach, FrancescCuezva, José M.Marcadors bioquímicsDermatomiositisMiositisMalalties muscularsBiochemical markersDermatomyositisMyositisMuscular DiseasesBackground Metabolic alterations play a role in the development of inflammatory myopathies (IMs). Herein, we have investigated through a multiplex assay whether proteins of energy metabolism could provide biomarkers of IMs. Methods A cohort of thirty-two muscle biopsies and forty plasma samples comprising polymyositis (PM), dermatomyositis (DM) and sporadic inclusion body myositis (sIBM) and control donors was interrogated with monoclonal antibodies against proteins of energy metabolism using reverse phase protein microarrays (RPPA). Results When compared to controls the expression of the proteins is not significantly affected in the muscle of PM patients. However, the expression of β-actin is significantly increased in DM and sIBM in consistence with muscle and fiber regeneration. Concurrently, the expression of some proteins involved in glucose metabolism displayed a significant reduction in muscle of sIBM suggesting a repression of glycolytic metabolism in these patients. In contrasts to these findings, the expression of the glycolytic pyruvate kinase isoform M2 (PKM2) and of the mitochondrial ATPase Inhibitor Factor 1 (IF1) and Hsp60 were significantly augmented in DM when compared to other IMs in accordance with a metabolic shift prone to cancer development. PKM2 alone or in combination with other biomarkers allowed the discrimination of control and IMs with very high (>95%) sensitivity and specificity. Unfortunately, plasma levels of PKM2 were not significantly altered in DM patients to recommend its use as a non-invasive biomarker of the disease. Conclusions Expression of proteins of energy metabolism in muscle enabled discrimination of patients with IMs. RPPA identified the glycolysis promoting PKM2 and IF1 proteins as specific biomarkers of dermatomyositis, providing a biochemical link of this IM with oncogenesis.BioMed Central2017201720172017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfhttps://hdl.handle.net/2445/109650Articles publicats en revistes (Medicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1186/s12967-017-1136-5Journal of Translational Medicine, 2017, vol. 15, num. 29https://doi.org/10.1186/s12967-017-1136-5cc-by (c) Santacatterina, Fulvio et al., 2017http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1096502026-05-29T05:05:01Z
dc.title.none.fl_str_mv Pyruvate kinase M2 and the mitochondrial ATPase Inhibitory Factor 1 provide novel biomarkers of dermatomyositis: a metabolic link to oncogenesis.
title Pyruvate kinase M2 and the mitochondrial ATPase Inhibitory Factor 1 provide novel biomarkers of dermatomyositis: a metabolic link to oncogenesis.
spellingShingle Pyruvate kinase M2 and the mitochondrial ATPase Inhibitory Factor 1 provide novel biomarkers of dermatomyositis: a metabolic link to oncogenesis.
Santacatterina, Fulvio
Marcadors bioquímics
Dermatomiositis
Miositis
Malalties musculars
Biochemical markers
Dermatomyositis
Myositis
Muscular Diseases
title_short Pyruvate kinase M2 and the mitochondrial ATPase Inhibitory Factor 1 provide novel biomarkers of dermatomyositis: a metabolic link to oncogenesis.
title_full Pyruvate kinase M2 and the mitochondrial ATPase Inhibitory Factor 1 provide novel biomarkers of dermatomyositis: a metabolic link to oncogenesis.
title_fullStr Pyruvate kinase M2 and the mitochondrial ATPase Inhibitory Factor 1 provide novel biomarkers of dermatomyositis: a metabolic link to oncogenesis.
title_full_unstemmed Pyruvate kinase M2 and the mitochondrial ATPase Inhibitory Factor 1 provide novel biomarkers of dermatomyositis: a metabolic link to oncogenesis.
title_sort Pyruvate kinase M2 and the mitochondrial ATPase Inhibitory Factor 1 provide novel biomarkers of dermatomyositis: a metabolic link to oncogenesis.
dc.creator.none.fl_str_mv Santacatterina, Fulvio
Sánchez Aragó, María
Catalán García, Marc
Garrabou Tornos, Glòria
Nuñez de Arenas, Cristina
Grau Junyent, Josep M. (Josep Maria)
Cardellach, Francesc
Cuezva, José M.
author Santacatterina, Fulvio
author_facet Santacatterina, Fulvio
Sánchez Aragó, María
Catalán García, Marc
Garrabou Tornos, Glòria
Nuñez de Arenas, Cristina
Grau Junyent, Josep M. (Josep Maria)
Cardellach, Francesc
Cuezva, José M.
author_role author
author2 Sánchez Aragó, María
Catalán García, Marc
Garrabou Tornos, Glòria
Nuñez de Arenas, Cristina
Grau Junyent, Josep M. (Josep Maria)
Cardellach, Francesc
Cuezva, José M.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Marcadors bioquímics
Dermatomiositis
Miositis
Malalties musculars
Biochemical markers
Dermatomyositis
Myositis
Muscular Diseases
topic Marcadors bioquímics
Dermatomiositis
Miositis
Malalties musculars
Biochemical markers
Dermatomyositis
Myositis
Muscular Diseases
description Background Metabolic alterations play a role in the development of inflammatory myopathies (IMs). Herein, we have investigated through a multiplex assay whether proteins of energy metabolism could provide biomarkers of IMs. Methods A cohort of thirty-two muscle biopsies and forty plasma samples comprising polymyositis (PM), dermatomyositis (DM) and sporadic inclusion body myositis (sIBM) and control donors was interrogated with monoclonal antibodies against proteins of energy metabolism using reverse phase protein microarrays (RPPA). Results When compared to controls the expression of the proteins is not significantly affected in the muscle of PM patients. However, the expression of β-actin is significantly increased in DM and sIBM in consistence with muscle and fiber regeneration. Concurrently, the expression of some proteins involved in glucose metabolism displayed a significant reduction in muscle of sIBM suggesting a repression of glycolytic metabolism in these patients. In contrasts to these findings, the expression of the glycolytic pyruvate kinase isoform M2 (PKM2) and of the mitochondrial ATPase Inhibitor Factor 1 (IF1) and Hsp60 were significantly augmented in DM when compared to other IMs in accordance with a metabolic shift prone to cancer development. PKM2 alone or in combination with other biomarkers allowed the discrimination of control and IMs with very high (>95%) sensitivity and specificity. Unfortunately, plasma levels of PKM2 were not significantly altered in DM patients to recommend its use as a non-invasive biomarker of the disease. Conclusions Expression of proteins of energy metabolism in muscle enabled discrimination of patients with IMs. RPPA identified the glycolysis promoting PKM2 and IF1 proteins as specific biomarkers of dermatomyositis, providing a biochemical link of this IM with oncogenesis.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/109650
url https://hdl.handle.net/2445/109650
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12967-017-1136-5
Journal of Translational Medicine, 2017, vol. 15, num. 29
https://doi.org/10.1186/s12967-017-1136-5
dc.rights.none.fl_str_mv cc-by (c) Santacatterina, Fulvio et al., 2017
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Santacatterina, Fulvio et al., 2017
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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