Preprint Review Version 1 This version is not peer-reviewed

Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants

Version 1 : Received: 20 February 2020 / Approved: 24 February 2020 / Online: 24 February 2020 (02:48:00 CET)

A peer-reviewed article of this Preprint also exists.

Lalmanach, G.; Saidi, A.; Bigot, P.; Chazeirat, T.; Lecaille, F.; Wartenberg, M. Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants. Int. J. Mol. Sci. 2020, 21, 1944. Lalmanach, G.; Saidi, A.; Bigot, P.; Chazeirat, T.; Lecaille, F.; Wartenberg, M. Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants. Int. J. Mol. Sci. 2020, 21, 1944.

Journal reference: Int. J. Mol. Sci. 2020, 21, 1944
DOI: 10.3390/ijms21061944

Abstract

Besides their primary involvement in the recycling and degradation of proteins in endo-lysosomal compartments but also in specialized biological functions, cysteine cathepsins are pivotal proteolytic contributors of various deleterious diseases. While the molecular mechanisms of regulation by their natural inhibitors have been exhaustively studied, less is currently known about how their enzymatic activity is modulated during the redox imbalance associated with an oxidative stress and their exposure resistance to oxidants. More specifically, there is only patchy information on the regulation of lung cysteine cathepsins, while the respiratory system is directly exposed to countless exogenous oxidants contained in dust, tobacco, combustion fumes, and industrial or domestic particles. Papain-like enzymes (clan CA, family C1, subfamily C1A) encompass a conserved catalytic thiolate-imidazolium pair (Cys25-His159) in their active site. Despite the sulfhydryl group (with a low acidic pKa) is a potent nucleophile highly susceptible to chemical modifications, some cysteine cathepsins reveal an unanticipated resistance to oxidative stress. Beside an introductory chapter and a peculiar attention to lung cysteine cathepsins, the purpose of this review is to afford a concise update of the current knowledge on molecular mechanisms associated to the regulation of cysteine cathepsins by redox balance and by oxidants (e.g. Michael acceptors, reactive oxygen and nitrogen species).

Subject Areas

cathepsin; chronic obstructive pulmonary disease (COPD); cigarette smoke; cysteine; cysteine protease; emphysema; oxidation; proteolysis; ROS; thiol

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