bims-noxint 2021-11-28 papers

Issue of 2021‒11‒28
two papers selected by
Laia Caja Puigsubira
Uppsala University

Antioxidants (Basel). 2021 Nov 18. pii: 1833. [Epub ahead of print]10(11):

Di-Tyrosine Crosslinking and NOX4 Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis.

Sanja Blaskovic, Yves Donati, Isabelle Ruchonnet-Metrailler, Tamara Seredenina, Karl-Heinz Krause, Jean-Claude Pache, Dan Adler, Constance Barazzone-Argiroffo, Vincent Jaquet.

Idiopathic pulmonary fibrosis (IPF) is a noninflammatory progressive lung disease. Oxidative damage is a hallmark of IPF, but the sources and consequences of oxidant generation in the lungs are unclear. In this study, we addressed the link between the H2O2-generating enzyme NADPH oxidase 4 (NOX4) and di-tyrosine (DT), an oxidative post-translational modification in IPF lungs. We performed immunohistochemical staining for DT and NOX4 in pulmonary tissue from patients with IPF and controls using validated antibodies. In the healthy lung, DT showed little or no staining and NOX4 was mostly present in normal vascular endothelium. On the other hand, both markers were detected in several cell types in the IPF patients, including vascular smooth muscle cells and epithelium (bronchial cells and epithelial cells type II). The link between NOX4 and DT was addressed in human fibroblasts deficient for NOX4 activity (mutation in the CYBA gene). Induction of NOX4 by Transforming growth factor beta 1 (TGFβ1) in fibroblasts led to moderate DT staining after the addition of a heme-containing peroxidase in control cells but not in the fibroblasts deficient for NOX4 activity. Our data indicate that DT is a histological marker of IPF and that NOX4 can generate a sufficient amount of H2O2 for DT formation in vitro.

Keywords: NADPH oxidase; NOX4; di-tyrosine; human lung tissue; idiopathic pulmonary fibrosis; immunohistochemistry

DOI: https://doi.org/10.3390/antiox10111833

Antioxidants (Basel). 2021 Nov 11. pii: 1799. [Epub ahead of print]10(11):

Redox Dysregulation in Aging and COPD: Role of NOX Enzymes and Implications for Antioxidant Strategies.

Caspar Schiffers, Niki L Reynaert, Emiel F M Wouters, Albert van der Vliet.

With a rapidly growing elderly human population, the incidence of age-related lung diseases such as chronic obstructive pulmonary disease (COPD) continues to rise. It is widely believed that reactive oxygen species (ROS) play an important role in ageing and in age-related disease, and approaches of antioxidant supplementation have been touted as useful strategies to mitigate age-related disease progression, although success of such strategies has been very limited to date. Involvement of ROS in ageing is largely attributed to mitochondrial dysfunction and impaired adaptive antioxidant responses. NADPH oxidase (NOX) enzymes represent an important enzyme family that generates ROS in a regulated fashion for purposes of oxidative host defense and redox-based signalling, however, the associations of NOX enzymes with lung ageing or age-related lung disease have to date only been minimally addressed. The present review will focus on our current understanding of the impact of ageing on NOX biology and its consequences for age-related lung disease, particularly COPD, and will also discuss the implications of altered NOX biology for current and future antioxidant-based strategies aimed at treating these diseases.

Keywords: COPD; DUOX1; NADPH oxidase; ageing; antioxidants; oxidative stress; redox signalling

DOI: https://doi.org/10.3390/antiox10111799