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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1994-5-18
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pubmed:abstractText |
The lanosterol demethylation intermediate 3 beta-hydroxylanost-8-en-32-al is a known suppressor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), the rate-limiting enzyme of cholesterol biosynthesis. Studies on the mechanism of action of this compound have been hampered by its rapid metabolism. As one approach to this problem, the effects of 3 beta-hydroxy-lanost-8-en-32-al on HMGR gene expression were examined using a mutant cell line which lacks lanosterol 14 alpha-methyl demethylase activity. Data are presented which suggest that 3 beta-hydroxy-lanost-8-en-32-al inhibits HMGR gene expression by reducing the translational efficiency of the HMGR mRNA. We have recently reported that 15 alpha-fluoro-3 beta-hydroxy-lanost-7-en-32-aldehyde, a compound which is structurally similar to 3 beta-hydroxy-lanost-8-en-32-aldehyde, suppresses HMGR activity in cultured Chinese hamster ovary cells by a posttranscriptional process, inhibiting translation without affecting either transcription or enzyme degradation (Trzaskos et al., 1993, J. Biol. Chem. 268, 22591-22599). In contrast to the results obtained with the 15 alpha-fluorolanostenol, the lanostenol 32-aldehyde increased the rate of degradation of HMGR in a manner similar to that reported for oxycholesterols. These data suggest that 15 alpha-fluoro-3 beta-hydroxy-lanost-7-en-32-aldehyde and 3 beta-hydroxy-lanost-8-en-32-aldehyde, although structurally similar posttranscriptional regulators of HMGR suppress enzyme activity, at least in part, by different mechanisms.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl CoA Reductases,
http://linkedlifedata.com/resource/pubmed/chemical/Lanosterol,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol 14-Demethylase,
http://linkedlifedata.com/resource/pubmed/chemical/lanosten-3-ol-32-al
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0003-9861
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
310
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
152-7
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:8161198-Animals,
pubmed-meshheading:8161198-CHO Cells,
pubmed-meshheading:8161198-Cholesterol,
pubmed-meshheading:8161198-Cricetinae,
pubmed-meshheading:8161198-Cytochrome P-450 Enzyme System,
pubmed-meshheading:8161198-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:8161198-Hydroxymethylglutaryl CoA Reductases,
pubmed-meshheading:8161198-Lanosterol,
pubmed-meshheading:8161198-Oxidoreductases,
pubmed-meshheading:8161198-Protein Biosynthesis,
pubmed-meshheading:8161198-RNA, Messenger,
pubmed-meshheading:8161198-RNA Processing, Post-Transcriptional,
pubmed-meshheading:8161198-Sterol 14-Demethylase
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pubmed:year |
1994
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pubmed:articleTitle |
Post-transcriptional regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by 3 beta-hydroxy-lanost-8-en-32-al, an intermediate in the conversion of lanosterol to cholesterol.
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pubmed:affiliation |
Biology Department, West Virginia University, Morgantown 26506-6057.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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