[PUBLICATION] Oxidation of cathepsin S by major chemicals of cigarette smoke


on the April 27, 2020

Collaborative research project led by Dr. G. Almanach (Université de Tours, Tours, France; INSERM, UMR1100, Centre d'Etude des Pathologies Respiratoires, Team « Mécanismes Protéolytiques dans l'Inflammation ») in which Dr. Nadal-Desbarats participated

Oxidation of cathepsin S by major chemicals of cigarette smoke


Lung cysteine cathepsin S (CatS) that is a potent elastase plays a deleterious role in alveolar remodeling during smoke-induced emphysema. Despite the presence of a reactive nucleophilic cysteine (Cys25) within its active site, most of its elastinolytic activity is preserved after exposure to cigarette smoke extract (CSE), a major source of sulfhydryl oxidants. This result led us to decipher CatS resistance to major and representative CSE oxidants: hydrogen peroxide, formaldehyde, acrolein and peroxynitrite. CatS was inactivated by hydrogen peroxide, peroxynitrite and acrolein in a time- and dose-dependent manner, while formaldehyde was a weaker oxidant. Hydrogen peroxide, but not CSE, formaldehyde, and peroxynitrite impaired the autocatalytic maturation of pro-CatS, whereas acrolein prevented the formation of mature CatS without hindering the initial step of the two-step autocatalytic process. Far-UV CD spectra analysis supported that oxidation by CSE and hydrogen peroxide did not led to a structural alteration of CatS, despite a notable increase of protein carbonylation, a major hallmark of oxidative damage. Evaluation of the oxidation status of Cys25 by specific biotinylated redox sensing probes suggested the formation of sulfenic acid followed by a slower conversion to sulfinic acid after incubation with hydrogen peroxide. Addition of reducing reagents (dithiothreitol, glutathione and N-acetyl cysteine) led to a partial recovery of CatS activity following incubation with CSE, hydrogen peroxide and peroxynitrite. Current results provide some mechanistic evidence of CatS stability and activity in the presence of CSE, supporting its harmful contribution to the pathophysiology of emphysema.

Copyright © 2020 Elsevier Inc. All rights reserved.

#smoke #oxidation #cigarette #cathepsinS

Contact :
Dr. Lydie Nadal-Desbarats :