The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Polyunsaturated Fatty Acids Suppress Hepatic Sterol Regulatory Element-binding Protein-1 Expression by Accelerating Transcript Decay
Open accessAbstract
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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Cited by
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
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SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
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A lipidomic analysis of nonalcoholic fatty liver disease
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The Opposing Effects of N-3 and n-6 Fatty Acids
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Enzymes of triacylglycerol synthesis and their regulation
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Metadata
- Authors
- Xu, J., Teran-Garcia, M., Park, J. H. Y., Nakamura, M. T., & Clarke, S. D.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-03
- Volume
- 276
- Issue
- 13
- Pages
- 9800-9807
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1984418452
- Cited by
- 276
- References
- 38
- FWCI
- 22.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Xu, J., Teran-Garcia, M., Park, J. H. Y., Nakamura, M. T., & Clarke, S. D. (2001). Polyunsaturated Fatty Acids Suppress Hepatic Sterol Regulatory Element-binding Protein-1 Expression by Accelerating Transcript Decay. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m008973200
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