Preclinical research of a new therapy for Gaucher's disease with F213I mutation.
- Author:
Lin HOU
1
;
Ohno KOUSAKU
Author Information
- Publication Type:Journal Article
- MeSH: Amino Acid Substitution; Blotting, Western; Cells, Cultured; Enzyme Induction; drug effects; Gaucher Disease; drug therapy; enzymology; genetics; Glucosylceramidase; biosynthesis; genetics; metabolism; Glucosylceramides; metabolism; pharmacology; Humans; Immunohistochemistry; Mutation; Substrate Specificity
- From: Chinese Journal of Medical Genetics 2003;20(5):381-384
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo design and make trial of a new therapy for Gaucher disease.
METHODSA 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.
RESULTSIt 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.
CONCLUSIONThe low molecular compound analogous to beta-Glc substrate (GCA ) may be a new therapeutic strategy for Gaucher's disease with F213I mutation.
