Imperial College London
Portrait Picture

ProfessorIanAdcock

Faculty of Medicine, National Heart & Lung Institute

Professor of Respiratory Cell & Molecular Biology
 
 
 
//

Contact

 

+44 (0)20 7594 7840ian.adcock Website

 
 
//

Location

 

304Guy Scadding BuildingRoyal Brompton Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Michaeloudes:2022:10.1016/j.mam.2021.101026,
author = {Michaeloudes, C and Abubakar-Waziri, H and Lakhdar, R and Raby, K and Dixey, P and Adcock, IM and Mumby, S and Bhavsar, PK and Chung, KF},
doi = {10.1016/j.mam.2021.101026},
journal = {Molecular Aspects of Medicine},
title = {Molecular mechanisms of oxidative stress in asthma},
url = {http://dx.doi.org/10.1016/j.mam.2021.101026},
volume = {85},
year = {2022}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The lungs are exposed to reactive oxygen species oxygen (ROS) produced as a result of inhalation of oxygen, as well as smoke and other air pollutants. Cell metabolism and the NADPH oxidases (Nox) generate low levels of intracellular ROS that act as signal transduction mediators by inducing oxidative modifications of histones, enzymes and transcription factors. Redox signalling is also regulated by localised production and sensing of ROS in mitochondria, the endoplasmic reticulum (ER) and inside the nucleus. Intracellular ROS are maintained at low levels through the action of a battery of enzymatic and non-enzymatic antioxidants. Asthma is a heterogeneous airway inflammatory disease with different immune endotypes; these include atopic or non-atopic Th2 type immune response associated with eosinophilia, or a non-Th2 response associated with neutrophilia. Airway remodelling and hyperresponsiveness accompany the inflammatory response in asthma. Over-production of ROS resulting from infiltrating immune cells, particularly eosinophils and neutrophils, and a concomitant impairment of antioxidant responses lead to development of oxidative stress in asthma. Oxidative stress is augmented in severe asthma and during exacerbations, as well as by air pollution and obesity, and causes oxidative damage of tissues promoting airway inflammation and hyperresponsiveness. Furthermore, deregulated Nox activity, mitochondrial dysfunction, ER stress and/or oxidative DNA damage, resulting from exposure to irritants, inflammatory mediators or obesity, may lead to redox-dependent changes in cell signalling. ROS play a central role in airway epithelium-mediated sensing, development of innate and adaptive immune responses, and airway remodelling and hyperresponsiveness. Nonetheless, antioxidant compounds have proven clinically ineffective as therapeutic agents for asthma, partly due to issues with stability and in vivo metabolism of these compounds. The compartmentalised nature of ROS product
AU  - Michaeloudes,C
AU  - Abubakar-Waziri,H
AU  - Lakhdar,R
AU  - Raby,K
AU  - Dixey,P
AU  - Adcock,IM
AU  - Mumby,S
AU  - Bhavsar,PK
AU  - Chung,KF
DO  - 10.1016/j.mam.2021.101026
PY  - 2022///
SN  - 0098-2997
TI  - Molecular mechanisms of oxidative stress in asthma
T2  - Molecular Aspects of Medicine
UR  - http://dx.doi.org/10.1016/j.mam.2021.101026
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34625291
UR  - http://hdl.handle.net/10044/1/92284
VL  - 85
ER  -
Download