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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-6-26
pubmed:abstractText
Treatment of neonatal rats with U18666A, an inhibitor of desmosterol delta24-reductase, results in accumulation of desmosterol (delta5,24) and depletion of cholesterol (delta5) in various bodily tissues and also causes cataracts. We evaluated the effects of U18666A on the sterol composition, de novo sterol synthesis, and histological structure of the retina. Neonatal Sprague-Dawley rats were injected subcutaneously with U18666A (15 mg/kg, in olive oil ) every other day from birth through 3 wk of age; in parallel, control rats received olive oil alone. At 21 d, treated and control groups each were subdivided into two groups: one group of each was injected intravitreally with [3H]acetate; retinas were removed 20 h later and nonsaponifiable lipids (NSL) were analyzed by radio-high-performance liquid chromatography. The other group was injected intravitreally with [3H]leucine; 4 d later, one eye of each animal was evaluated by light and electron microscopy and light microscopic autoradiography, while contralateral retinas and rod outer segment (ROS) membranes prepared therefrom were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/fluorography. In the treated group, the delta5/delta5,24 mole ratio of retinas was ca. 1.0, and >88% of the NSL radioactivity was in delta5,24; in contrast, control retinas had delta5/delta5,24 >170, with >80% of the NSL radioactivity in delta5. Retinal histology, ultrastructure, ROS renewal rates, and rhodopsin synthesis and intracellular trafficking were comparable in both treated and control animals. These results suggest that desmosterol can either substitute functionally for cholesterol in the retina or it can complement subthreshold levels of cholesterol by sterol synergism.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0024-4201
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
289-96
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Cholesterol synthesis in the vertebrate retina: effects of U18666A on rat retinal structure, photoreceptor membrane assembly, and sterol metabolism and composition.
pubmed:affiliation
Saint Louis University Eye Institute, Saint Louis University School of Medicine, Missouri 63104-1540. Fliesler@slu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.