NADPH oxidase subunit NOXO1 is a target for emphysema treatment in COPD

被引：0

作者：

Michael Seimetz

Natascha Sommer

Mariola Bednorz

Oleg Pak

Christine Veith

Stefan Hadzic

Marija Gredic

Nirmal Parajuli

Baktybek Kojonazarov

Simone Kraut

Jochen Wilhelm

Fenja Knoepp

Ingrid Henneke

Alexandra Pichl

Zeki I. Kanbagli

Susan Scheibe

Athanasios Fysikopoulos

Cheng-Yu Wu

Walter Klepetko

Peter Jaksch

Christina Eichstaedt

Ekkehard Grünig

Katrin Hinderhofer

Miklós Geiszt

Niklas Müller

Flavia Rezende

Giulia Buchmann

Ilka Wittig

Matthias Hecker

Andreas Hecker

Winfried Padberg

Peter Dorfmüller

Stefan Gattenlöhner

Claus F. Vogelmeier

Andreas Günther

Srikanth Karnati

Eveline Baumgart-Vogt

Ralph T. Schermuly

Hossein A. Ghofrani

Werner Seeger

Katrin Schröder

Friedrich Grimminger

Ralf P. Brandes

Norbert Weissmann

机构：

[1] Justus-Liebig University,Department of Cardiothoracic Surgery

[2] Excellence Cluster Cardio-Pulmonary Institute (CPI),Department of Physiology, Faculty of Medicine

[3] Universities of Giessen and Marburg Lung Center (UGMLC),Institute for Cardiovascular Physiology

[4] Member of the German Center for Lung Research (DZL),Department of Surgery

[5] Division of Basic Biomedical Science,Department of Pathology

[6] University of South Dakota,Department of Medicine

[7] Sanford School of Medicine,Institute of Anatomy and Cell Biology

[8] Justus-Liebig University,Department of Medicine

[9] Institute for Lung Health,undefined

[10] University Hospital of Vienna,undefined

[11] Center for Pulmonary Hypertension,undefined

[12] Thoraxklinik at Heidelberg University Hospital,undefined

[13] Laboratory of Molecular Genetic Diagnostics,undefined

[14] Institute of Human Genetics,undefined

[15] Heidelberg University,undefined

[16] Translational Lung Research Center Heidelberg (TLRC),undefined

[17] German Center for Lung Research (DZL),undefined

[18] Semmelweis University,undefined

[19] Goethe University,undefined

[20] Functional Proteomics Group,undefined

[21] Goethe-University Hospital,undefined

[22] Justus-Liebig University,undefined

[23] Justus-Liebig University,undefined

[24] Pulmonary and Critical Care Medicine,undefined

[25] German Center for Lung Research,undefined

[26] University of Marburg,undefined

[27] Institute for Anatomy and Cell Biology II,undefined

[28] Division of Medical Cell Biology,undefined

[29] Justus-Liebig University Giessen,undefined

[30] Julius-Maximilians-University Würzburg,undefined

[31] Imperial College London,undefined

[32] Max Planck Institute for Heart and Lung Research,undefined

来源：

Nature Metabolism | 2020年 / 2卷

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摘要：

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.

引用

页码：532 / 546

页数：14

共 79 条

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