Document Detail


Cholestenoic Acid is an important elimination product of cholesterol in the retina: comparison of retinal cholesterol metabolism with that in the brain.
MedLine Citation:
PMID:  20881306     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Accumulating evidence indicates a link between cholesterol and age-related macular degeneration. Yet, little is known about cholesterol elimination from the retina and retinal pigment epithelium (RPE), the two layers that are damaged in this blinding disease. Several different pathways of enzymatic cholesterol removal exist in extraocular tissues. The authors tested whether metabolites from these pathways could also be quantified in the bovine and human retina and RPE. For comparison, they measured cholesterol oxidation products in two regions of the bovine and human brain and in the bovine liver and adrenal glands.
METHODS: Sterol quantification was carried out by isotope dilution gas chromatography-mass spectrometry. Bovine tissues were used first to optimize analytical procedures and to investigate postmortem changes in oxysterol concentrations. Then human specimens were analyzed for oxysterol concentrations.
RESULTS: Qualitatively, oxysterol profiles were similar in the bovine and human tissues. In the human retina and RPE, the authors could not detect 27-hydroxycholesterol but unexpectedly found that its oxidation product, 5-cholestenoic acid, is the most abundant oxysterol, varying up to threefold in different persons. 24S-Hydroxysterol and pregnenolone were also present in the retina, but at much lower quantities and without significant interindividual variability. In the brain, the predominant oxysterol was 24S-hydroxycholesterol.
CONCLUSIONS: The oxysterol profile of the retina suggests that all known pathways of cholesterol elimination in extraocular organs are operative in the retina and that they likely vary depending on specific cell type. However, overall oxidation to 5-cholestenoic acid appears to be the predominant mechanism for cholesterol elimination from this organ.
Authors:
Natalia Mast; Rachel Reem; Ilya Bederman; Suber Huang; Pier Luigi DiPatre; Ingemar Bjorkhem; Irina A Pikuleva
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-01
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  52     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-02-02     Completed Date:  2011-03-09     Revised Date:  2012-05-24    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  594-603     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenal Glands / metabolism
Aged
Aged, 80 and over
Animals
Brain / metabolism*
Cattle
Cholesterol / analogs & derivatives*,  metabolism*
Cholesterol Side-Chain Cleavage Enzyme / metabolism
Cytochrome P-450 CYP27A1 / metabolism
Female
Gas Chromatography-Mass Spectrometry
Humans
Hydroxycholesterols / metabolism
Liver / metabolism
Male
Middle Aged
Retina / metabolism*
Retinal Pigment Epithelium / metabolism
Steroid Hydroxylases / metabolism
Grant Support
ID/Acronym/Agency:
AG024336/AG/NIA NIH HHS; EY018383/EY/NEI NIH HHS; T32 EY007157/EY/NEI NIH HHS; T32 EY007157-09/EY/NEI NIH HHS; T32 EY007157-10/EY/NEI NIH HHS; T32 EY07157/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Hydroxycholesterols; 474-73-7/24-hydroxycholesterol; 57-88-5/Cholesterol; 6561-58-6/3-hydroxy-5-cholestenoic acid; EC 1.14.-/Cytochrome P-450 CYP27A1; EC 1.14.-/Steroid Hydroxylases; EC 1.14.-/cholesterol 24-hydroxylase; EC 1.14.15.6/Cholesterol Side-Chain Cleavage Enzyme
Comments/Corrections

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


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