Substrate stimulation of 7 alpha-hydroxylase, an enzyme located in the cholesterol-poor endoplasmic reticulum.

Straka, M S; Junker, L; Zacarro, L; Zogg, Donald L.; Dueland, Svein; Everson, Gregory T.; Davis, Roger J.

doi:10.1016/s0021-9258(19)39091-x

Cited by 50 publications

(9 citation statements)

References 48 publications

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“…More detailed studies indicated that as the duration of the removal of bile from the rat increased, the amount of bile acid that was excreted increased up to a maximal level (56). The findings showing higher rates of bile acid synthesis and/or expression of CYP7A1 in animals fed bile acid sequestrants (e.g., cholestyramine), which bind bile acids and prevent their reabsorption via the intestine, pro-vides further evidence for bile acid negative feedback regulation (57)(58)(59).…”

Section: End-product (Bile Acid) Negative Feedback Regulation Of Cyp7a1mentioning

confidence: 90%

“…Further analysis shows that the ability to decrease bile acid synthesis correlates with the relative hydrophobicity, as determined by elution of the bile acid on reverse-phase chromatography (63). Administration of taurocholate in the rat diet decreased bile acid synthesis and the expression of CYP7A1 mRNA and enzyme activity (58,64). The ability of individual bile acids, fed as a dietary component, to decrease CYP7A1 also correlates with the relative amount of hydrophobicity (65).…”

Section: End-product (Bile Acid) Negative Feedback Regulation Of Cyp7a1mentioning

confidence: 98%

“…It has been proposed that the ability of certain species, strains, and individuals to increase the production of bile acids in response to augmented ingestion of cholesterol is a major predictor of their susceptibility to diet-induced hypercholesterolemia (78). Rats and mice, which are generally noted as being resistant to diet-induced hypercholesterolemia, display increased expression of CYP7A1 and the production of bile acids in response to cholesterol-rich diets (58,(79)(80)(81)(82)(83)(84)(85)(86). The induction of CYP7A1 and bile acid synthesis by dietary cholesterol has also been observed in dogs (87) and in a hypercholesterolemia-resistant strain of rabbits (88).…”

Section: Induction Of Cyp7a1 and Bile Acid Synthesis By Dietary Cholesterolmentioning

confidence: 99%

“…One important consideration in evaluating individual responses to dietary cholesterol is the relative amount that is administered. In general, cholesterol feeding studies in rodents consist of feeding a diet containing ‫ف‬ 2% cholesterol (58,86), which represents a ‫ف‬ 100-fold increase compared with normal rodent diets. In contrast, humans are usually given much smaller increments in dietary cholesterol ( ‫ف‬ 3-fold increases over normal intake) (98).…”

Section: Induction Of Cyp7a1 and Bile Acid Synthesis By Dietary Cholesterolmentioning

confidence: 99%

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Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHP

Davis

Miyake

Hui

et al. 2002

Journal of Lipid Research

155

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Cholesterol-7 ␣ -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 ␣ and interleukin-1 ␤ , act upon liver parenchymal cells causing a rapid repression of the CYP7A1 gene. -

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Section: End-product (Bile Acid) Negative Feedback Regulation Of Cyp7a1mentioning

confidence: 90%

Section: End-product (Bile Acid) Negative Feedback Regulation Of Cyp7a1mentioning

confidence: 98%

Section: Induction Of Cyp7a1 and Bile Acid Synthesis By Dietary Cholesterolmentioning

confidence: 99%

Section: Induction Of Cyp7a1 and Bile Acid Synthesis By Dietary Cholesterolmentioning

confidence: 99%

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Regulation of cholesterol-7α-hydroxylase: BAREly missing a SHP

Davis

Miyake

Hui

et al. 2002

Journal of Lipid Research

155

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“…Values are reported as the mean Ϯ SD for three individual culture dishes. For the cholesterol C7 ␣ H activity assay microsomes were isolated and assayed by the method described in Straka et al (26).…”

Section: Enzyme Assaysmentioning

confidence: 99%

In nonhepatic cells, cholesterol 7α-hydroxylase induces the expression of genes regulating cholesterol biosynthesis, efflux, and homeostasis

Spitsen

Dueland²,

Krisans

et al. 2000

Journal of Lipid Research

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CHO cells expressing the liver-specific gene product cholesterol-7 ␣ -hydroxylase showed a 6-fold increase in the biosynthesis of [ 14 C]cholesterol from [ 14 C]acetate, as well as increased enzymatic activities of 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase and squalene synthase. Cells expressing cholesterol-7 ␣ -hydroxylase contained less sterol response element-binding protein 1 (SREBP1) precursor, whereas the cellular content of mature SREBP1, as well as the mRNAs of cholesterol biosynthetic genes (HMG-CoA reductase and squalene synthase), were all increased ϳ 3-fold. Cells expressing cholesterol-7 ␣ -hydroxylase displayed greater activities of luciferase reporters containing the SREBP-dependent promoter elements derived from HMG-CoA reductase and farnesyl diphosphate synthase, in spite of accumulating significantly more free and esterified cholesterol and 7 ␣ -hydroxycholesterol. While cells expressing cholesterol-7 ␣ -hydroxylase displayed increased SREBPdependent transcription, sterol-mediated repression of SREBP-dependent transcription by LDL-cholesterol and exogenous oxysterols was similar in both cell types. Cells expressing cholesterol-7 ␣ -hydroxylase displayed greater rates of secretion of cholesterol as well as increased expression of the ABC1 cassette protein mRNA. Adding 25hydroxycholesterol to the culture medium of both cell types increased the expression of ABC1 cassette protein mRNA. The combined data suggest that in nonhepatic CHO cells multiple regulatory processes sensitive to cellular sterols act independently to coordinately maintain cellular cholesterol homeostasis. -Spitsen, G.

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