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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
2001-3-27
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pubmed:abstractText |
The reduction in hepatic abundance of sterol regulatory element binding protein-1 (SREBP-1) mRNA and protein associated with the ingestion of polyunsaturated fatty acids (PUFA) appears to be largely responsible for the PUFA-dependent inhibition of lipogenic gene transcription. Our initial studies indicated that the induction of SREBP-1 expression by insulin and glucose was blocked by PUFA. Nuclear run-on assays suggested PUFA reduced SREBP-1 mRNA by post-transcriptional mechanisms. In this report we demonstrate that PUFA enhance the decay of both SREBP-1a and -1c. When rat hepatocytes in monolayer culture were treated with albumin-bound 20:4(n-6) or 20:5(n-3) the half-life of total SREBP-1 mRNA was reduced by 50%. Ribonuclease protection assays revealed that the decay of SREBP-1c mRNA was more sensitive to PUFA than was SREBP-1a, i.e. the half-life of SREBP-1c and -1a was reduced from 10.0 to 4.6 h and 11.6 to 7.6 h, respectively. Interestingly, treating the hepatocytes with the translational inhibitor, cycloheximide, prevented the PUFA-dependent decay of SREBP-1. This suggests that SREBP-1 mRNA may need to undergo translation to enter the decay process, or that the decay process requires the synthesis of a rapidly turning over protein. Although the mechanism by which PUFA accelerate SREBP-1 mRNA decay remains to be determined, cloning and sequencing of the 3'-untranslated region for the rat SREBP-1 transcript revealed the presence of an A-U-rich region that is characteristic of a destablizing element.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Amanitins,
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Unsaturated,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleic Acid Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/SREBF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Srebf1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9800-7
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11124951-3' Untranslated Regions,
pubmed-meshheading:11124951-Amanitins,
pubmed-meshheading:11124951-Amino Acid Sequence,
pubmed-meshheading:11124951-Animals,
pubmed-meshheading:11124951-Base Sequence,
pubmed-meshheading:11124951-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:11124951-Cell Nucleus,
pubmed-meshheading:11124951-Cells, Cultured,
pubmed-meshheading:11124951-Cloning, Molecular,
pubmed-meshheading:11124951-Cycloheximide,
pubmed-meshheading:11124951-DNA-Binding Proteins,
pubmed-meshheading:11124951-Fatty Acids, Unsaturated,
pubmed-meshheading:11124951-Gene Expression Regulation,
pubmed-meshheading:11124951-Glucose,
pubmed-meshheading:11124951-Hepatocytes,
pubmed-meshheading:11124951-Humans,
pubmed-meshheading:11124951-Insulin,
pubmed-meshheading:11124951-Liver,
pubmed-meshheading:11124951-Male,
pubmed-meshheading:11124951-Microsomes,
pubmed-meshheading:11124951-Molecular Sequence Data,
pubmed-meshheading:11124951-Nucleic Acid Synthesis Inhibitors,
pubmed-meshheading:11124951-Protein Biosynthesis,
pubmed-meshheading:11124951-Protein Synthesis Inhibitors,
pubmed-meshheading:11124951-RNA, Messenger,
pubmed-meshheading:11124951-RNA Processing, Post-Transcriptional,
pubmed-meshheading:11124951-Rats,
pubmed-meshheading:11124951-Rats, Sprague-Dawley,
pubmed-meshheading:11124951-Ribonucleases,
pubmed-meshheading:11124951-Sequence Analysis, DNA,
pubmed-meshheading:11124951-Sequence Homology, Amino Acid,
pubmed-meshheading:11124951-Sterol Regulatory Element Binding Protein 1,
pubmed-meshheading:11124951-Time Factors,
pubmed-meshheading:11124951-Transcription, Genetic,
pubmed-meshheading:11124951-Transcription Factors
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pubmed:year |
2001
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pubmed:articleTitle |
Polyunsaturated fatty acids suppress hepatic sterol regulatory element-binding protein-1 expression by accelerating transcript decay.
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pubmed:affiliation |
Division of Nutritional Sciences, and the Institute for Cellular and Molecular Biology, The University of Texas at Austin, 78712, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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