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:
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
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