[Preclinical research of a new therapy for Gaucher's disease with F213I mutation].
OBJECTIVE
To design and make trial of a new therapy for Gaucher disease.


METHODS
A substrate analogue of beta-Glc (glucocerebroside analogue, GCA) was used as a molecular chaperon. Normal and mutant skin fibroblasts were cultured with or without GCA. The activity of beta-Glc was assayed by fluorescent enzymologic techniques. The amount of beta-Glc was determined using Western blot. The beta -Glc was localized by double cell stain experiment. The degradation of glucocerebroside was assessed by thin layer chromatography (TLC) experiment using 14C-Serine.


RESULTS
It was found that GCA could enhance the activity and amount of beta-Glc with F213I mutation. It also promoted the beta-Glc with F213I mutation to the lysosome and accelerated the degradation of glucocerebroside.


CONCLUSIONS
The low molecular compound analogous to beta-Glc substrate (GCA ) may be a new therapeutic strategy for Gaucher's disease with F213I mutation.
Hou
Lin
L
Department of Biochemistry, Medical College, Qingdao University, Qingdao, Shandong, 266021 PR China. qdhoulin@yahoo.com
Kousaku
Ohno
O
D019943:Amino Acid Substitution; D015153:Blotting, Western; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D005776:Gaucher Disease / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D005962:Glucosylceramidase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005963:Glucosylceramides / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D013379:Substrate Specificity
D005963:Glucosylceramides; D005962:Glucosylceramidase