Impact of β-galactosidase mutations on the expression of the canine lysosomal multienzyme complex
| Autor: | Mihaela Kreutzer, Tosso Leeb, Somporn Techangamsuwan, Robert Kreutzer, Adrian C. Sewell, Wolfgang Baumgärtner |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Lysosomal multienzyme complex
Mutant Cathepsin A Neuraminidase Biology Gene Expression Regulation Enzymologic NEU1 Differential expression Dogs Neuraminidase 1 Multienzyme Complexes GM1-gangliosidosis Lysosomal storage disease medicine Animals RNA Messenger Molecular Biology Regulation of gene expression Mannose 6-phosphate receptor Protective protein/cathepsin A Fibroblasts medicine.disease beta-Galactosidase Molecular biology Biochemistry GLB1 Mutation Molecular Medicine β-galactosidase variant Lysosomes |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1792(10):982-987 |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2009.07.004 |
| Popis: | beta-galactosidase (GLB1) forms a functional lysosomal multienzyme complex with lysosomal protective protein (PPCA) and neuraminidase 1 (NEU1) which is important for its intracellular processing and activity. Mutations in the beta-galactosidase gene cause the lysosomal storage disease G(M1)-gangliosidosis. In order to identify additional molecular changes associated with the presence of beta-galactosidase mutations, the expression of canine lysosomal multienzyme complex components in GLB1(+/+), GLB1(+/-) and GLB1(-/-) fibroblasts was investigated by quantitative RT-PCR, Western blot and enzymatic assays. Quantitative RT-PCR revealed differential regulation of total beta-galactosidase, beta-galactosidase variants and protective protein for beta-galactosidase gene (PPGB) in GLB1(+/-) and GLB1(-/-) compared to GLB1(+/+) fibroblasts. Furthermore, it was shown that PPGB levels gradually increased with the number of mutant beta-galactosidase alleles while no change in the NEU1 expression was observed. This is the first study that simultaneously examine the effect of GLB1(+/+), GLB1(+/-) and GLB1(-/-) genotypes on the expression of lysosomal multienzyme complex components. The findings reveal a possible adaptive process in GLB1 homozygous mutant and heterozygous individuals that could facilitate the design of efficient therapeutic strategies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect