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Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants
Besides their primary involvement in the recycling and degradation of proteins in endo-lysosomal compartments and also in specialized biological functions, cysteine cathepsins are pivotal proteolytic contributors of various deleterious diseases. While the molecular mechanisms of regulation via their...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139492/ https://www.ncbi.nlm.nih.gov/pubmed/32178437 http://dx.doi.org/10.3390/ijms21061944 |
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author | Lalmanach, Gilles Saidi, Ahlame Bigot, Paul Chazeirat, Thibault Lecaille, Fabien Wartenberg, Mylène |
author_facet | Lalmanach, Gilles Saidi, Ahlame Bigot, Paul Chazeirat, Thibault Lecaille, Fabien Wartenberg, Mylène |
author_sort | Lalmanach, Gilles |
collection | PubMed |
description | Besides their primary involvement in the recycling and degradation of proteins in endo-lysosomal compartments and also in specialized biological functions, cysteine cathepsins are pivotal proteolytic contributors of various deleterious diseases. While the molecular mechanisms of regulation via their natural inhibitors have been exhaustively studied, less is currently known about how their enzymatic activity is modulated during the redox imbalance associated with 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. Although 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. Besides an introductory chapter and 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 with the regulation of cysteine cathepsins by redox balance and by oxidants (e.g., Michael acceptors, reactive oxygen, and nitrogen species). |
format | Online Article Text |
id | pubmed-7139492 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71394922020-04-10 Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants Lalmanach, Gilles Saidi, Ahlame Bigot, Paul Chazeirat, Thibault Lecaille, Fabien Wartenberg, Mylène Int J Mol Sci Review Besides their primary involvement in the recycling and degradation of proteins in endo-lysosomal compartments and also in specialized biological functions, cysteine cathepsins are pivotal proteolytic contributors of various deleterious diseases. While the molecular mechanisms of regulation via their natural inhibitors have been exhaustively studied, less is currently known about how their enzymatic activity is modulated during the redox imbalance associated with 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. Although 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. Besides an introductory chapter and 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 with the regulation of cysteine cathepsins by redox balance and by oxidants (e.g., Michael acceptors, reactive oxygen, and nitrogen species). MDPI 2020-03-12 /pmc/articles/PMC7139492/ /pubmed/32178437 http://dx.doi.org/10.3390/ijms21061944 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Lalmanach, Gilles Saidi, Ahlame Bigot, Paul Chazeirat, Thibault Lecaille, Fabien Wartenberg, Mylène Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants |
title | Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants |
title_full | Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants |
title_fullStr | Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants |
title_full_unstemmed | Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants |
title_short | Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants |
title_sort | regulation of the proteolytic activity of cysteine cathepsins by oxidants |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139492/ https://www.ncbi.nlm.nih.gov/pubmed/32178437 http://dx.doi.org/10.3390/ijms21061944 |
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