Document Detail


Synthesis and use of novel fluorescent glycosphingolipids for estimating beta-glucosidase activity in vitro in the absence of detergents and subtyping Gaucher disease variants following administration into intact cells.
MedLine Citation:
PMID:  8399329     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Two novel fluorescent glycolipids, LRO-glucosylceramide (LRO-GC) and LRO-trihexosylceramide (LRO-THC) were synthesized and utilized for estimating activities of the lysosomal, acid beta-glucosidase in cell extracts and intact skin fibroblasts, derived from normal individuals and patients with Gaucher disease subtypes. The uniqueness of the glycolipids is the fact that a fluorescent probe (lissamine rhodamine) is linked in a sulfonylamide linkage to the sphingosyl residue of the sphingolipid. Thus, the product of enzymatic hydrolysis, lissamine rhodamine sulfonylamido sphingosine (LRO-ceramide) cannot be further hydrolyzed and remains a metabolic end product. A unique property of LRO-GC as a substrate for the lysosomal, acid beta-glucosidase in vitro was the observation that enzymatic hydrolysis occurs in the absence of detergents and that hydrolytic rates are, in fact, reduced in the presence of Triton X-100 and/or sodium taurocholate. Also, both glycolipids penetrated the membrane of intact fibroblasts in the absence of serum and were hydrolyzed in lysosomes of the intact cells. The rates of intracellular hydrolysis decreased with the severity of the Gaucher disease subtypes. Using LRO-THC as substrate, the intracellular ratio of LRO-ceramide to LRO-glucosylceramide was an indicator for the specific GD-subtype.
Authors:
V Agmon; S Cherbu; A Dagan; M Grace; G A Grabowski; S Gatt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1170     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1993 Sep 
Date Detail:
Created Date:  1993-11-01     Completed Date:  1993-11-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  72-9     Citation Subset:  IM    
Affiliation:
Department of Membrane Biochemistry and Neurochemistry, Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
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MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
Detergents
Fluorescent Dyes / chemical synthesis*
Gaucher Disease / classification,  enzymology*,  genetics
Genotype
Glucosylceramides / chemical synthesis
Glycosphingolipids / chemical synthesis*
Humans
Point Mutation
Rhodamines / chemical synthesis
Skin / enzymology
Trihexosylceramides / chemical synthesis
beta-Glucosidase / analysis*,  genetics
Grant Support
ID/Acronym/Agency:
DK 36729/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Detergents; 0/Fluorescent Dyes; 0/Glucosylceramides; 0/Glycosphingolipids; 0/Rhodamines; 0/Trihexosylceramides; 0/lissamine rhodamine sulfonylamidosphingosyl-trihexosylceramide; 0/lissamine rhodamine-sulfonylamidosphingosyl beta-glucoside; EC 3.2.1.21/beta-Glucosidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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