NADPH oxidase subunit NOXO1 is a target for emphysema treatment in COPD
| Autor: | Norbert Weissmann, Miklós Geiszt, Susan Scheibe, Mariola Bednorz, Christina A. Eichstaedt, Marija Gredic, Ekkehard Grünig, Simone Kraut, Niklas Müller, Hossein Ardeschir Ghofrani, Natascha Sommer, Nirmal Parajuli, Ralph T. Schermuly, Christine Veith, Werner Seeger, Friedrich Grimminger, Stefan Hadzic, Fenja Knoepp, Athanasios Fysikopoulos, Giulia K. Buchmann, Oleg Pak, Peter Dorfmüller, Flávia Rezende, Jochen Wilhelm, Peter Jaksch, Alexandra Pichl, Matthias Hecker, Katrin Schröder, Andreas Hecker, Srikanth Karnati, Winfried Padberg, Baktybek Kojonazarov, Cheng-Yu Wu, Stefan Gattenlöhner, Zeki I. Kanbagli, Ralf P. Brandes, Andreas Günther, Eveline Baumgart-Vogt, Ingrid Henneke, Claus Vogelmeier, Ilka Wittig, Walter Klepetko, Michael Seimetz, Katrin Hinderhofer |
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| Rok vydání: | 2020 |
| Předmět: |
Endocrinology
Diabetes and Metabolism Hypertension Pulmonary Apoptosis Pharmacology Nitric Oxide Nitric oxide chemistry.chemical_compound Mice Pulmonary Disease Chronic Obstructive Superoxides Physiology (medical) Peroxynitrous Acid Internal Medicine Medicine Animals Humans Lung emphysema CYBB Adaptor Proteins Signal Transducing Emphysema Mice Knockout NADPH oxidase biology business.industry Superoxide Nitrotyrosine Cell Biology respiratory system respiratory tract diseases Nitric oxide synthase Mice Inbred C57BL chemistry biology.protein Tyrosine Tobacco Smoke Pollution business Peroxynitrite Signal Transduction |
| Zdroj: | Nature metabolism. 2(6) |
| ISSN: | 2522-5812 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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