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

Adaptor Proteins, Signal Transducing / drug effects Animals Apoptosis / drug effects Emphysema / drug therapy Humans Hypertension, Pulmonary / genetics Mice Mice, Inbred C57BL Mice, Knockout Nitric Oxide / metabolism Peroxynitrous Acid / metabolism Pulmonary Disease, Chronic Obstructive / complications Signal Transduction / genetics Superoxides / metabolism Tobacco Smoke Pollution / adverse effects Tyrosine / analogs & derivatives

Journal

Nature metabolism

ISSN: 2522-5812

Titre abrégé: Nat Metab

Pays: Germany

ID NLM: 101736592

Informations de publication

Date de publication:
06 2020

Historique:

received: 25 02 2020

accepted: 27 04 2020

entrez: 23 7 2020

pubmed: 23 7 2020

medline: 1 1 2021

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s42255-020-0215-8 PMID: 32694733

pubmed: 32694733

doi: 10.1038/s42255-020-0215-8

pii: 10.1038/s42255-020-0215-8

doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0

NOXO1 protein, human 0

Noxo1 protein, mouse 0

Tobacco Smoke Pollution 0

Superoxides 11062-77-4

Peroxynitrous Acid 14691-52-2

Nitric Oxide 31C4KY9ESH

3-nitrotyrosine 3604-79-3

Tyrosine 42HK56048U

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

532-546

Commentaires et corrections

Type : ErratumIn

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