Abstract
Introduction: Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease. The initiating factor could be a damage of alveolar epithelial cells promoting release of TGF-β and other profibrotic mediators which results in continuous deposition of excess extracellular matrix and collagen, causing repetitive micro-injury to lung tissue. Oxidant stress enhances fibroblast proliferation and collagen formation by activating latent TGF-β. The excessive levels of mtROS are not only a key player in profibrotic signaling but also promote mtDNA damage that can lead to mutations resulting in the synthesis of defective electron transport chain (ETC) components. A systemic accumulation of ROS and mtDNA mutations in lymphocytes of IPF patients has already been presented by our team.
Aim: To investigate the activity of the Complex I (NADH-coenzyme Q oxidoreductase), one of the five protein ETC complexes, as its deficiency is the most common enzymatic defect for a variety of clinical entities.
Methods: Blood lymphocytes were isolated from 16 patients with IPF and 30 healthy controls. The complex I activity was determined by measuring the rotenone-sensitive oxidation of NADH to NAD+ at 340 nm with 380nm as the reference wavelength.
Results: Patients with IPF had significantly lower NADH-quinone oxidoreductase complex I activity compared to controls (12.07±3.7 mU/mgr vs. 57.2±4.8 mU/mg, p<0.001, respectively).
Conclusions: Reduced activity of complex I has been detected in blood lymphocytes of IPF patients compared to controls. These mtDNA and respiratory chain insults could account for a self-perpetuating release of endogenous ROS as an important contributor of IPF pathology.
Footnotes
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3379.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2020