Arylsulfatase K inactivation causes mucopolysaccharidosis due to deficient glucuronate desulfation of heparan and chondroitin sulfate

Trabszo C, Ramms B, Chopra P, Lüllmann-Rauch R, Stroobants S, Sproß J, Jeschke A, Schinke T, Boons G-J, Esko J, Lübke T, et al. (2020)
Biochemical Journal.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Trabszo, ChristofUniBi; Ramms, Bastian; Chopra, Pradeep; Lüllmann-Rauch, Renate; Stroobants, Stijn; Sproß, JensUniBi; Jeschke, Anke; Schinke, Thorsten; Boons, Geert-Jan; Esko, Jeffrey; Lübke, TorbenUniBi; Dierks, ThomasUniBi
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Abstract / Bemerkung
Mucopolysaccharidoses comprise a group of rare metabolic diseases, in which the lysosomal degradation of glycosaminoglycans (GAGs) is impaired due to genetically inherited defects of lysosomal enzymes involved in GAG catabolism. The resulting intralysosomal accumulation of GAG-derived metabolites consequently manifests in neurological symptoms and also peripheral abnormalities in various tissues like liver, kidney, spleen and bone. As each GAG consists of differently sulfated disaccharide units, it needs a specific, but also partly overlapping set of lysosomal enzymes to accomplish their complete degradation. Recently, we identified and characterized the lysosomal enzyme arylsulfatase K (Arsk) exhibiting glucuronate-2-sulfatase activity as needed for the degradation of heparan sulfate, chondroitin sulfate and dermatan sulfate. In the present study, we investigated the physiological relevance of Arsk by means of a constitutive Arsk knockout mouse model. A complete lack of glucuronate desulfation was demonstrated by a specific enzyme activity assay. Arsk-deficient mice show, in an organ-specific manner, a moderate accumulation of heparan sulfate and chondroitin sulfate metabolites characterized by 2-O-sulfated glucuronate moieties at their non-reducing ends. Pathophysiological studies reflect a rather mild phenotype including behavioral changes. Interestingly, no prominent lysosomal storage pathology like bone abnormalities were detected. Our results from the Arsk mouse model suggest a new although mild form of MPS, which we designate MPS type IIB. Copyright 2020 The Author(s).
Stichworte
Cell Biology; Biochemistry; Molecular Biology
Erscheinungsjahr
2020
Zeitschriftentitel
Biochemical Journal
ISSN
0264-6021
eISSN
1470-8728
Page URI
https://pub.uni-bielefeld.de/record/2945876

Zitieren

Trabszo C, Ramms B, Chopra P, et al. Arylsulfatase K inactivation causes mucopolysaccharidosis due to deficient glucuronate desulfation of heparan and chondroitin sulfate. Biochemical Journal. 2020.
Trabszo, C., Ramms, B., Chopra, P., Lüllmann-Rauch, R., Stroobants, S., Sproß, J., Jeschke, A., et al. (2020). Arylsulfatase K inactivation causes mucopolysaccharidosis due to deficient glucuronate desulfation of heparan and chondroitin sulfate. Biochemical Journal. doi:10.1042/bcj20200546
Trabszo, C., Ramms, B., Chopra, P., Lüllmann-Rauch, R., Stroobants, S., Sproß, J., Jeschke, A., Schinke, T., Boons, G. - J., Esko, J., et al. (2020). Arylsulfatase K inactivation causes mucopolysaccharidosis due to deficient glucuronate desulfation of heparan and chondroitin sulfate. Biochemical Journal.
Trabszo, C., et al., 2020. Arylsulfatase K inactivation causes mucopolysaccharidosis due to deficient glucuronate desulfation of heparan and chondroitin sulfate. Biochemical Journal.
C. Trabszo, et al., “Arylsulfatase K inactivation causes mucopolysaccharidosis due to deficient glucuronate desulfation of heparan and chondroitin sulfate”, Biochemical Journal, 2020.
Trabszo, C., Ramms, B., Chopra, P., Lüllmann-Rauch, R., Stroobants, S., Sproß, J., Jeschke, A., Schinke, T., Boons, G.-J., Esko, J., Lübke, T., Dierks, T.: Arylsulfatase K inactivation causes mucopolysaccharidosis due to deficient glucuronate desulfation of heparan and chondroitin sulfate. Biochemical Journal. (2020).
Trabszo, Christof, Ramms, Bastian, Chopra, Pradeep, Lüllmann-Rauch, Renate, Stroobants, Stijn, Sproß, Jens, Jeschke, Anke, Schinke, Thorsten, Boons, Geert-Jan, Esko, Jeffrey, Lübke, Torben, and Dierks, Thomas. “Arylsulfatase K inactivation causes mucopolysaccharidosis due to deficient glucuronate desulfation of heparan and chondroitin sulfate”. Biochemical Journal (2020).

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