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NADPH oxidase subunit NOXO1 is a target for emphysema treatment in COPD.
Seimetz, Michael; Sommer, Natascha; Bednorz, Mariola; Pak, Oleg; Veith, Christine; Hadzic, Stefan; Gredic, Marija; Parajuli, Nirmal; Kojonazarov, Baktybek; Kraut, Simone; Wilhelm, Jochen; Knoepp, Fenja; Henneke, Ingrid; Pichl, Alexandra; Kanbagli, Zeki I; Scheibe, Susan; Fysikopoulos, Athanasios; Wu, Cheng-Yu; Klepetko, Walter; Jaksch, Peter; Eichstaedt, Christina; Grünig, Ekkehard; Hinderhofer, Katrin; Geiszt, Miklós; Müller, Niklas; Rezende, Flavia; Buchmann, Giulia; Wittig, Ilka; Hecker, Matthias; Hecker, Andreas; Padberg, Winfried; Dorfmüller, Peter; Gattenlöhner, Stefan; Vogelmeier, Claus F; Günther, Andreas; Karnati, Srikanth; Baumgart-Vogt, Eveline; Schermuly, Ralph T; Ghofrani, Hossein A; Seeger, Werner; Schröder, Katrin; Grimminger, Friedrich; Brandes, Ralf P; Weissmann, Norbert.
Afiliación
  • Seimetz M; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Sommer N; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Bednorz M; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Pak O; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Veith C; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Hadzic S; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Gredic M; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Parajuli N; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Kojonazarov B; Division of Basic Biomedical Science, University of South Dakota, Sanford School of Medicine, Vermillion, SD, USA.
  • Kraut S; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Wilhelm J; Justus-Liebig University, Institute for Lung Health, Giessen, Germany.
  • Knoepp F; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Henneke I; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Pichl A; Justus-Liebig University, Institute for Lung Health, Giessen, Germany.
  • Kanbagli ZI; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Scheibe S; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Fysikopoulos A; Justus-Liebig University, Institute for Lung Health, Giessen, Germany.
  • Wu CY; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Klepetko W; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Jaksch P; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Eichstaedt C; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Grünig E; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Hinderhofer K; Department of Cardiothoracic Surgery, University Hospital of Vienna, Vienna, Austria.
  • Geiszt M; Department of Cardiothoracic Surgery, University Hospital of Vienna, Vienna, Austria.
  • Müller N; Center for Pulmonary Hypertension, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany.
  • Rezende F; Laboratory of Molecular Genetic Diagnostics, Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
  • Buchmann G; Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.
  • Wittig I; Center for Pulmonary Hypertension, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany.
  • Hecker M; Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.
  • Hecker A; Laboratory of Molecular Genetic Diagnostics, Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
  • Padberg W; Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
  • Dorfmüller P; Institute for Cardiovascular Physiology, Goethe University, Frankfurt, Germany.
  • Gattenlöhner S; Institute for Cardiovascular Physiology, Goethe University, Frankfurt, Germany.
  • Vogelmeier CF; Institute for Cardiovascular Physiology, Goethe University, Frankfurt, Germany.
  • Günther A; Functional Proteomics Group, Goethe-University Hospital, Frankfurt am Main, Germany.
  • Karnati S; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Baumgart-Vogt E; Department of Surgery, Justus-Liebig University, Giessen, Germany.
  • Schermuly RT; Department of Surgery, Justus-Liebig University, Giessen, Germany.
  • Ghofrani HA; Department of Pathology, Justus-Liebig University, Giessen, Germany.
  • Seeger W; Department of Pathology, Justus-Liebig University, Giessen, Germany.
  • Schröder K; Department of Medicine, Pulmonary and Critical Care Medicine, German Center for Lung Research, University of Marburg, Marburg, Germany.
  • Grimminger F; Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
  • Brandes RP; Institute for Anatomy and Cell Biology II, Division of Medical Cell Biology, Justus-Liebig University Giessen, Giessen, Germany.
  • Weissmann N; Institute of Anatomy and Cell Biology, Julius-Maximilians-University Würzburg, Würzburg, Germany.
Nat Metab ; 2(6): 532-546, 2020 06.
Article en En | MEDLINE | ID: mdl-32694733
ABSTRACT
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and death worldwide. Peroxynitrite, formed from nitric oxide, which is derived from inducible nitric oxide synthase, and superoxide, has been implicated in the development of emphysema, but the source of the superoxide was hitherto not characterized. Here, we identify the non-phagocytic NADPH oxidase organizer 1 (NOXO1) as the superoxide source and an essential driver of smoke-induced emphysema and pulmonary hypertension development in mice. NOXO1 is consistently upregulated in two models of lung emphysema, Cybb (also known as NADPH oxidase 2, Nox2)-knockout mice and wild-type mice with tobacco-smoke-induced emphysema, and in human COPD. Noxo1-knockout mice are protected against tobacco-smoke-induced pulmonary hypertension and emphysema. Quantification of superoxide, nitrotyrosine and multiple NOXO1-dependent signalling pathways confirm that peroxynitrite formation from nitric oxide and superoxide is a driver of lung emphysema. Our results suggest that NOXO1 may have potential as a therapeutic target in emphysema.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad Pulmonar Obstructiva Crónica / Proteínas Adaptadoras Transductoras de Señales / Enfisema Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: Nat Metab Año: 2020 Tipo del documento: Article País de afiliación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad Pulmonar Obstructiva Crónica / Proteínas Adaptadoras Transductoras de Señales / Enfisema Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: Nat Metab Año: 2020 Tipo del documento: Article País de afiliación: Alemania