The abnormal accumulation 1 of heparan sulfate in patients with mucopolysaccharidosis prevents the elastolytic activity of cathepsin V

Authors
Chazeirat, T.
Denamur, S.
Bojarski, K.K.
Andrault, P.-M.
Sizaret, D.
Zhang, F.
Saidi, A.
Tardieu, M.
Linhardt, Robert J.
Labarthe, F.
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2020
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
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Full Citation
The abnormal accumulation 1 of heparan sulfate in patients with mucopolysaccharidosis prevents the elastolytic activity of cathepsin V, T. Chazeirat, S. Denamur, K. K. Bojarski, P.-M. Andrault, D. Sizaret, F. Zhang, A. Saidi, M. Tardieu, R. J. Linhardt, F. Labarthe, D. Brömme, S. A. Samsonov, G. Lalmanach, F. Lecaille, Carbohydrate Polymers, 253, 117261, 2020.
Abstract
Mucopolysaccharidosis (MPS) are rare inherited diseases characterized by accumulation of lysosomal glycosaminoglycans, including heparan sulfate (HS). Patients exhibit progressive multi-visceral dysfunction and shortened lifespan mainly due to a severe cardiac/respiratory decline. Cathepsin V (CatV) is a potent elastolytic protease implicated in extracellular matrix (ECM) remodeling. Whether CatV is inactivated by HS in lungs from MPS patients remained unknown. Herein, CatV colocalized with HS in MPS bronchial epithelial cells. HS level correlated positively with the severity of respiratory symptoms and negatively to the overall endopeptidase activity of cysteine cathepsins. HS bound tightly to CatV and impaired its activity. Withdrawal of HS by glycosidases preserved exogenous CatV activity, while addition of Surfen, a HS antagonist, restored elastolytic CatV-like activity in MPS samples. Our data suggest that the pathophysiological accumulation of HS may be deleterious for CatV-mediated ECM remodeling and for lung tissue homeostasis, thus contributing to respiratory disorders associated to MPS diseases.
Description
Carbohydrate Polymers, 253, 117261
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
https://harc.rpi.edu/
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