Neurocan is a New Substrate for the ADAMTS12 Metalloprotease: Potential Implications in Neuropathies.
ADAMTS Proteins
/ biosynthesis
Animals
Cell Adhesion
Cell Line, Tumor
Cell Movement
Chondroitin Sulfate Proteoglycans
/ genetics
Cranial Nerve Diseases
/ genetics
Gene Expression Regulation
Humans
Lectins, C-Type
/ genetics
Mice
Nerve Tissue Proteins
/ genetics
Neurocan
Proteoglycans
/ genetics
Proteolysis
ADAMTS
Extracellular matrix
Metalloprotease
Neurocan
Neurocanase
Journal
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
ISSN: 1421-9778
Titre abrégé: Cell Physiol Biochem
Pays: Germany
ID NLM: 9113221
Informations de publication
Date de publication:
2019
2019
Historique:
received:
03
07
2018
accepted:
21
02
2019
entrez:
13
4
2019
pubmed:
13
4
2019
medline:
3
5
2019
Statut:
ppublish
Résumé
The composition of the extracellular matrix (ECM) in the central nervous system (CNS) has several features that make it unique. For instance, it is remarkable for the presence of proteoglycans such as versican, brevican, and neurocan, some of which have been identified as substrates of different members of the ADAMTS family of secreted metalloproteases. Previous studies have associated ADAMTSs with the repair of the CNS, including recovery following degradation of glial scar tissue and the stimulation of axonal growth after brain injury. However, the involvement of ADAMTSs in diseases of the CNS is complex and not understood fully, and a current challenge is unraveling the precise roles of these metalloproteases in the brain. ADAMTS12 and neurocan gene expression was examined by quantitative PCR. Western blot analysis was employed to detect ADAMTS12 and neurocan protein expression in cell lines, and immunostaining techniques were used to detect neurocan in mouse brain tissues. Neurocan cleavage using recombinant ADAMTS1, ADAMTS4, ADAMTS5, and ADAMTS12 metalloproteases was evaluated by western blotting. Cell adhesion and migration were assessed using uncoated culture dishes or dishes coated with Matrigel or ECM components. We identified neurocan as a novel component of brain ECM that can be cleaved by ADAMTS12. In addition, we showed that neurocan cleavage by ADAMTS12 altered the adhesive properties of the human neuroglioma H4 cell line. Moreover, immunohistochemical analysis of Adamts12-deficient mice revealed the significant accumulation of neurocan in the brain of neonatal mice. Overall, our results suggest that ADAMTS12 could be involved in the repair of the CNS through its ability to degrade neurocan. Moreover, it can be inferred that alterations in neurocan degradation processes could be associated with the pathogenesis of neurological disorders.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
The composition of the extracellular matrix (ECM) in the central nervous system (CNS) has several features that make it unique. For instance, it is remarkable for the presence of proteoglycans such as versican, brevican, and neurocan, some of which have been identified as substrates of different members of the ADAMTS family of secreted metalloproteases. Previous studies have associated ADAMTSs with the repair of the CNS, including recovery following degradation of glial scar tissue and the stimulation of axonal growth after brain injury. However, the involvement of ADAMTSs in diseases of the CNS is complex and not understood fully, and a current challenge is unraveling the precise roles of these metalloproteases in the brain.
METHODS
METHODS
ADAMTS12 and neurocan gene expression was examined by quantitative PCR. Western blot analysis was employed to detect ADAMTS12 and neurocan protein expression in cell lines, and immunostaining techniques were used to detect neurocan in mouse brain tissues. Neurocan cleavage using recombinant ADAMTS1, ADAMTS4, ADAMTS5, and ADAMTS12 metalloproteases was evaluated by western blotting. Cell adhesion and migration were assessed using uncoated culture dishes or dishes coated with Matrigel or ECM components.
RESULTS
RESULTS
We identified neurocan as a novel component of brain ECM that can be cleaved by ADAMTS12. In addition, we showed that neurocan cleavage by ADAMTS12 altered the adhesive properties of the human neuroglioma H4 cell line. Moreover, immunohistochemical analysis of Adamts12-deficient mice revealed the significant accumulation of neurocan in the brain of neonatal mice.
CONCLUSION
CONCLUSIONS
Overall, our results suggest that ADAMTS12 could be involved in the repair of the CNS through its ability to degrade neurocan. Moreover, it can be inferred that alterations in neurocan degradation processes could be associated with the pathogenesis of neurological disorders.
Substances chimiques
Chondroitin Sulfate Proteoglycans
0
Lectins, C-Type
0
Ncan protein, mouse
0
Nerve Tissue Proteins
0
Neurocan
0
Proteoglycans
0
NCAN protein, human
148684-98-4
ADAMTS Proteins
EC 3.4.24.-
ADAMTS12 protein, human
EC 3.4.24.-
Adamts12 protein, mouse
EC 3.4.24.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1003-1016Subventions
Organisme : Instituto Asturiano de Odontología
Pays : Spain
Informations de copyright
© Copyright by the Author(s). Published by Cell Physiol Biochem Press.
Déclaration de conflit d'intérêts
The authors declare that no conflicts of interest exist.