Document Detail


Comparison of effects of U18666A and enantiomeric U18666A on sterol synthesis and induction of apoptosis.
MedLine Citation:
PMID:  16149744     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Treatment of animals or cells with the amphipathic tertiary amine U18666A {3beta-[2-(diethylamino) ethoxy]androst-5-en-17-one} provides models for several human diseases (e.g., cataracts, Niemann-Pick disease, and epilepsy). Although U18666A can inhibit several enzymes in the cholesterol synthesis pathway, we hypothesized that induction of these varied conditions was due to physical effects of the amine rather than to inhibition of specific proteins. To test this possibility we compared the capacity of U18666A and its enantiomer, ent-U18666A, to inhibit net sterol synthesis and induce apoptosis in cultured bovine lens epithelial cells. Nonenantiospecific actions dependent on the physical properties of these mirror image molecules would be identical, but effects dependent upon enantiospecific interactions would be different for the enantiomers. At the same concentrations, both forms of the compound equally inhibited sterol synthesis and induced apoptosis. These observations supported a generalized mechanism of enzyme inhibition such as perturbation of the microenvironment of endoplasmic enzymes and alteration of membrane order, perhaps of the mitochondrial membrane, to explain induction of apoptosis.
Authors:
Richard J Cenedella; Patricia S Sexton; Kathiresan Krishnan; Douglas F Covey
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Lipids     Volume:  40     ISSN:  0024-4201     ISO Abbreviation:  Lipids     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-09-09     Completed Date:  2005-12-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0060450     Medline TA:  Lipids     Country:  United States    
Other Details:
Languages:  eng     Pagination:  635-40     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Kirksville College of Osteopathic Medicine, Kirksville, Missouri 63501, USA. rcenedella@atsu.edu
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MeSH Terms
Descriptor/Qualifier:
Androstenes / chemistry*,  pharmacology*
Animals
Apoptosis / drug effects*
Cattle
Cells, Cultured
Lens, Crystalline / drug effects,  metabolism,  pathology
Stereoisomerism
Sterols / biosynthesis*
Grant Support
ID/Acronym/Agency:
EY02568/EY/NEI NIH HHS; GM47969/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Androstenes; 0/Sterols; 3039-71-2/3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one

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


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