Cathepsin A contributes to left ventricular remodeling by degrading extracellular superoxide dismutase in mice.

EC-SOD carboxypeptidase cardiac hypertrophy cardiac remodeling cathepsin A extracellular matrix protein extracellular superoxide dismutase fibrosis heart disease heart failure left ventricular dysfunction oxidative stress oxygen radicals secretome superoxide dismutase (SOD)

Journal

The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R

Informations de publication

Date de publication:
04 09 2020
Historique:
received: 20 03 2020
revised: 29 06 2020
pubmed: 11 7 2020
medline: 28 1 2021
entrez: 11 7 2020
Statut: ppublish

Résumé

In the heart, the serine carboxypeptidase cathepsin A (CatA) is distributed between lysosomes and the extracellular matrix (ECM). CatA-mediated degradation of extracellular peptides may contribute to ECM remodeling and left ventricular (LV) dysfunction. Here, we aimed to evaluate the effects of CatA overexpression on LV remodeling. A proteomic analysis of the secretome of adult mouse cardiac fibroblasts upon digestion by CatA identified the extracellular antioxidant enzyme superoxide dismutase (EC-SOD) as a novel substrate of CatA, which decreased EC-SOD abundance 5-fold.

Identifiants

pubmed: 32647007
pii: S0021-9258(17)49977-7
doi: 10.1074/jbc.RA120.013488
pmc: PMC7476717
doi:

Substances chimiques

Sod3 protein, mouse EC 1.15.1.1
Superoxide Dismutase EC 1.15.1.1
Cathepsin A EC 3.4.16.5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

12605-12617

Subventions

Organisme : Medical Research Council
ID : MC_UP_1502/3
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/16/14/32397
Pays : United Kingdom

Informations de copyright

© 2020 Hohl et al.

Déclaration de conflit d'intérêts

Conflict of interest—Sven Ruf, Thomas Hübschle, and Thorsten Sadowski are employees of Sanofi-Aventis Deutschland GmbH. The other authors have not conflicts of interest.

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Auteurs

Mathias Hohl (M)

Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.

Manuel Mayr (M)

King's BHF Centre of Research Excellence, The James Black Centre, London, United Kingdom.

Lisa Lang (L)

Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.

Alexander G Nickel (AG)

Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.
Universitätsklinikum Würzburg, Deutsches Zentrum für Herzinsuffizienz (DZHI), Comprehensive Heart Failure Center (CHFC), Würzburg, Germany.

Javier Barallobre-Barreiro (J)

King's BHF Centre of Research Excellence, The James Black Centre, London, United Kingdom.

Xiaoke Yin (X)

King's BHF Centre of Research Excellence, The James Black Centre, London, United Kingdom.

Thimoteus Speer (T)

Klinik für Innere Medizin IV, Universität des Saarlandes, Homburg/Saar, Germany.

Simina-Ramona Selejan (SR)

Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.

Claudia Goettsch (C)

Medizinische Fakultät, Medizinische Klinik 1, Kardiologie, Universitätsklinikum, Aachen, Germany.

Katharina Erb (K)

Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.

Claudia Fecher-Trost (C)

Institut für Experimentelle und Klinische Pharmakologie und Toxikologie Universität des Saarlandes, Homburg/Saar, Germany.

Jan-Christian Reil (JC)

Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.
Klinik für Innere Medizin II, Universitäres Herzzentrum, Lübeck, Germany.

Benedikt Linz (B)

Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

Sven Ruf (S)

Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.

Thomas Hübschle (T)

Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.

Christoph Maack (C)

Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.
Universitätsklinikum Würzburg, Deutsches Zentrum für Herzinsuffizienz (DZHI), Comprehensive Heart Failure Center (CHFC), Würzburg, Germany.

Michael Böhm (M)

Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.

Thorsten Sadowski (T)

Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.

Dominik Linz (D)

Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany dominik.linz@mumc.nl.
University Maastricht, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands.
Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
Centre for Heart Rhythm Disorders, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia.

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Classifications MeSH