Document Detail


Metabolism of 27-, 25- and 24-hydroxycholesterol in rat glial cells and neurons.
MedLine Citation:
PMID:  9078259     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The metabolism of 27-, 25- and 24-hydroxycholesterol in cultures of rat astrocytes, Schwann cells and neurons was studied. 27- and 25-Hydroxycholesterol, but not 24-hydroxycholesterol, underwent 7 alpha-hydroxylation with subsequent oxidation to 7 alpha-hydroxy-3-oxo-delta 4 steroids in all three cell types. When cells were incubated for 24 h with 0.28 nmol of 27-hydroxycholesterol in 10 ml of medium, the rates of conversion into 7 alpha-hydroxylated metabolites were 0.21, 0.12 and 0.02 nmol/24 h per 10(6) cells in the media of astrocytes, Schwann cells and neurons respectively. The corresponding values for 25-hydroxycholesterol were 0.26, 0.16 and 0.04. A minor fraction of 27-hydroxycholesterol and its 7 alpha-hydroxylated metabolites was oxidized to 3 beta-hydroxy-5-cholestenoic acid. 3 beta, 7 alpha-dihydroxy-5-cholestenoic acid and 7 alpha-hydroxy-3-oxo-4-cholestenoic acid. In addition to the two hydroxycholesterols, other 3 beta-hydroxy-delta 4 steroids, dehydro-epiandrosterone, pregnenolone, 3 beta-hydroxy-5-cholestenoic acid and 3 beta-hydroxy-5-cholenoic acid underwent 7 alpha-hydroxylation. Competitive experiments did not distinguish between the presence of one or several 7 alpha-hydroxylases. In astrocyte incubations, 27-hydroxycholesterol also underwent 25-hydroxylation, and 12% of its metabolites carried a 25-hydroxy group. 25-Hydroxylation of added 24-hydroxycholesterol was also observed in the astrocyte incubations, as was the formation of 7 alpha, 25-dihydroxy-4-cholesten-3-one, 25-hydroxycholesterol and 7 alpha, 25-dihydroxycholesterol from endogenous precursor(s). Our study indicates that side-chain oxygenated cholesterol can undergo metabolic transformations that may be of importance for cholesterol homoeostasis in the brain.
Authors:
J Zhang; Y Akwa; M el-Etr; E E Baulieu; J Sjövall
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  322 ( Pt 1)     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1997 Feb 
Date Detail:
Created Date:  1997-04-15     Completed Date:  1997-04-15     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  175-84     Citation Subset:  IM    
Affiliation:
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Animals
Astrocytes / metabolism
Brain / metabolism
Cells, Cultured
Cholestenones / analysis
Cholesterol / analogs & derivatives,  metabolism
Cholic Acids / metabolism
Fetus
Hydroxycholesterols / metabolism*
Hydroxylation
Microsomes / metabolism
Neuroglia / metabolism*
Neurons / metabolism*
Rats
Rats, Sprague-Dawley
Schwann Cells / metabolism
Substrate Specificity
Chemical
Reg. No./Substance:
0/7,25-dihydroxy-4-cholesten-3-one; 0/Cholestenones; 0/Cholic Acids; 0/Hydroxycholesterols; 20380-11-4/27-hydroxycholesterol; 2140-46-7/25-hydroxycholesterol; 474-73-7/24-hydroxycholesterol; 5255-17-4/3 beta-hydroxy-delta 5-cholenic acid; 57-88-5/Cholesterol; 6561-58-6/3-hydroxy-5-cholestenoic acid
Comments/Corrections

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


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