Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHP
Cholesterol-7α-hydroxylase (CYP7A1) regulates the pathway through which cholesterol is converted into bile acids. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids have potent toxic properties (e.g., membrane...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2002-04-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520314826 |
| _version_ | 1818726927294267392 |
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| author | Roger A. Davis Jon H. Miyake To Yuen Hui Nathanael J. Spann |
| author_facet | Roger A. Davis Jon H. Miyake To Yuen Hui Nathanael J. Spann |
| author_sort | Roger A. Davis |
| collection | DOAJ |
| description | Cholesterol-7α-hydroxylase (CYP7A1) regulates the pathway through which cholesterol is converted into bile acids. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids have potent toxic properties (e.g., membrane disruption) and there are a plethora of mechanisms to limit their accumulation in blood and tissues. The discovery of farnesoid X receptor (FXR), the nuclear receptor activated specifically by bile acids, has opened new insights into these mechanisms. Bile acid activation of FXR has been shown to repress the expression of CYP7A1 via increasing the expression of small heterodimer partner (SHP), a non-DNA binding protein. The increased abundance of SHP causes it to associate with liver receptor homolog (LRH)-1, an obligate factor required for transcription of CYP7A1. Recent studies show there is an “FXR/SHP-independent” mechanism that also represses CYP7A1 expression. This “FXR/SHP-independent” pathway involves the interaction of bile acids with liver macrophages (i.e., Kupffer cells), which induces the expression, and secretion of cytokines. These inflammatory cytokines, which include tumor necrosis factor α and interleukin-1β, act upon liver parenchymal cells causing a rapid repression of the CYP7A1 gene.—Davis, R. A., J. H. Miyake, T. Y. Hui, and N. J. Spann. Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHP. J. Lipid Res. 2002. 43: 533–543. |
| first_indexed | 2024-12-17T22:05:59Z |
| format | Article |
| id | doaj.art-bd253b2ec095432bae8dbf9c55115441 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T22:05:59Z |
| publishDate | 2002-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-bd253b2ec095432bae8dbf9c551154412022-12-21T21:30:51ZengElsevierJournal of Lipid Research0022-22752002-04-01434533543Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHPRoger A. Davis0Jon H. Miyake1To Yuen Hui2Nathanael J. Spann3To whom correspondence should be addressed.; Cell and Molecular Biology Laboratory, Department of Biology, San Diego State University, San Diego, CA 92182Cell and Molecular Biology Laboratory, Department of Biology, San Diego State University, San Diego, CA 92182Cell and Molecular Biology Laboratory, Department of Biology, San Diego State University, San Diego, CA 92182Cell and Molecular Biology Laboratory, Department of Biology, San Diego State University, San Diego, CA 92182Cholesterol-7α-hydroxylase (CYP7A1) regulates the pathway through which cholesterol is converted into bile acids. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids have potent toxic properties (e.g., membrane disruption) and there are a plethora of mechanisms to limit their accumulation in blood and tissues. The discovery of farnesoid X receptor (FXR), the nuclear receptor activated specifically by bile acids, has opened new insights into these mechanisms. Bile acid activation of FXR has been shown to repress the expression of CYP7A1 via increasing the expression of small heterodimer partner (SHP), a non-DNA binding protein. The increased abundance of SHP causes it to associate with liver receptor homolog (LRH)-1, an obligate factor required for transcription of CYP7A1. Recent studies show there is an “FXR/SHP-independent” mechanism that also represses CYP7A1 expression. This “FXR/SHP-independent” pathway involves the interaction of bile acids with liver macrophages (i.e., Kupffer cells), which induces the expression, and secretion of cytokines. These inflammatory cytokines, which include tumor necrosis factor α and interleukin-1β, act upon liver parenchymal cells causing a rapid repression of the CYP7A1 gene.—Davis, R. A., J. H. Miyake, T. Y. Hui, and N. J. Spann. Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHP. J. Lipid Res. 2002. 43: 533–543.http://www.sciencedirect.com/science/article/pii/S0022227520314826bile acid biosynthesisFXRcytokines |
| spellingShingle | Roger A. Davis Jon H. Miyake To Yuen Hui Nathanael J. Spann Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHP Journal of Lipid Research bile acid biosynthesis FXR cytokines |
| title | Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHP |
| title_full | Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHP |
| title_fullStr | Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHP |
| title_full_unstemmed | Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHP |
| title_short | Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHP |
| title_sort | regulation of cholesterol 7α hydroxylase barely missing a shp |
| topic | bile acid biosynthesis FXR cytokines |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520314826 |
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