Abstract:
:Taurocholate, a relatively hydrophobic bile salt, is a potent down-regulator of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase (C7 alpha H), the rate-determining enzymes of the cholesterol and bile acid biosynthetic pathways, respectively. Inhibition of cholesterol synthesis with a bolus dose of mevinolin (lovastatin) a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, profoundly decreases the specific activity of cholesterol 7 alpha-hydroxylase and rate of bile acid synthesis in rats with complete biliary diversion. It is therefore conceivable that taurocholate may suppress cholesterol 7 alpha-hydroxylase primarily by down-regulating the activity of HMG-CoA reductase. To test this hypothesis, taurocholate was coinfused simultaneously to rats with chronic bile fistula with mevalonate (administered as mevalonolactone), an intermediate in the cholesterol biosynthetic pathway. Mevalonolactone was administered to provide a constant supply of newly synthesized cholesterol to cholesterol 7 alpha-hydroxylase, in order to overcome any inhibitory effect of taurocholate on HMG-Coa reductase. Infusions were started 72 h after biliary diversion, and carried out for an additional 48 h. Complete biliary diversion resulted in an increase in C7 alpha H specific activity (510%), protein mass (550%), steady-state mRNA levels (1430%), and transcriptional activities (330%) as compared to control rats with intact enterohepatic circulations. When rats with biliary diversion were infused intraduodenally with taurocholate, the specific activities of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities decreased by 75% (P less than 0.001) and 73% (P less than 0.001), respectively. Cholesterol 7 alpha-hydroxylase mass, mRNA, and transcriptional activity decreased after intraduodenal infusion of taurocholate to levels similar to those of rats with an intact enterohepatic circulation. The combination of constant infusion of mevalonate and taurocholate failed to reverse the inhibitory effects of taurocholate on cholesterol 7 alpha-hydroxylase activity, mRNA levels, and in vitro transcriptional rates. These data provide evidence that taurocholate represses cholesterol 7 alpha-hydroxylase at the level of gene transcription, and not via down-regulation of HMG-CoA reductase. Infusion of mevalonate alone to biliary diverted rats did not alter cholesterol 7 alpha-hydroxylase activity or mRNA levels, while leading to a 57% decrease in C7 alpha H gene transcription. This latter finding suggests that mevalonate or its metabolites may be capable of stabilizing C7 alpha H mRNA levels while down-regulating transcriptional activity.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Pandak WM,Vlahcevic ZR,Chiang JY,Heuman DM,Hylemon PBkeywords:
subject
Has Abstractpub_date
1992-05-01 00:00:00pages
659-68issue
5eissn
0022-2275issn
1539-7262journal_volume
33pub_type
杂志文章abstract::Chiral phase high performance liquid chromatographic resolution of sn-1,2(2,3)- and X-1,3-diacylglycerols generated by partial Grignard degradation from natural triacylglycerols was carried out using a chiral column (25 cm x 4.6 mm i.d.) containing (R)-(+)-1-(1-napthyl)ethylamine polymer chemically bonded to 300A wide...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
abstract::Methods were developed for the determination of HMG CoA (3-hydroxy-3-methylglutaryl CoA) reductase activity in subcellular fractions of intestinal mucosa and liver of Wistar strain rats. In the liver, reductase activity was located exclusively in the microsomal fraction. In the intestinal mucosa, activity was found in...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1972-05-01 00:00:00
abstract::ABCA12 mutations disrupt the skin barrier and cause harlequin ichthyosis. We previously showed Abca12(-/-) skin has increased glucosylceramide (GlcCer) and correspondingly lower amounts of ceramide (Cer). To examine why loss of ABCA12 leads to accumulation of GlcCer, de novo sphingolipid synthesis was assayed using [(...
journal_title:Journal of lipid research
pub_type: 杂志文章
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更新日期:2014-03-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M064758
更新日期:2016-04-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::Clostridium absonum was shown to metabolize primary bile acids to give rise to both 7-oxo bile acids and 7 beta-hydroxy (urso) bile acids. At relatively low redox potential (Eh) values, high yields of urso bile acids were achieved (60-75%). If, however, the Eh value of the culture was allowed to rise above approximate...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1982-07-01 00:00:00
abstract::A novel metabolite of d-delta-tocopherol was isolated from the urine of rats given d-3,4-[3H2]-delta-tocopherol intravenously. The metabolite was collected from the urine of rats given d-delta-tocopherol in the same manner as that of the labeled compound. It was found that the metabolites consisted of sulfate conjugat...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::Glycerolipid and apoB synthesis and secretion were examined in hepatocytes obtained from fetal, suckling (day 6), and adult rats in order to examine the developmental regulation of lipoprotein production. The capacity to synthesize [3H]triacylglycerol (from [3H]glycerol) followed the order: adult greater than day 6 gr...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::A reproducible cell culture system is described that allows the study of adipose conversion in fibroblast-like cells isolated by collagenase digestion of epididymal and perirenal adipose tissue from male rats weighing 70-200 g. Adipose conversion as measured by lipid accumulation and increase in glycerophosphate dehyd...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::Fatty acid binding protein 4 (FABP4), also known as adipocyte FABP or aP2, is secreted from adipocytes in association with lipolysis as a novel adipokine, and elevated serum FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the modulation of serum FABP4 lev...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M059469
更新日期:2015-12-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::The lipase superfamily includes three vertebrate and three invertebrate (dipteran) proteins that show significant amino acid sequence similarity to one another. The vertebrate proteins are lipoprotein lipase (LPL), hepatic lipase (HL), and pancreatic lipase (PL). The dipteran proteins are Drosophila yolk proteins 1, 2...
journal_title:Journal of lipid research
pub_type: 杂志文章,评审
doi:
更新日期:1992-02-01 00:00:00
abstract::ZR-78 and ZR-82 cells are two peroxisomal-deficient Chinese hamster ovary (CHO) cell mutants. These cells lack normal peroxisomes and show reduced levels of plasmalogen synthesis and other peroxisomal functions attributed to the deficiency of peroxisomal matrix enzymes. As we have recently identified two HMG-CoA reduc...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
abstract::Acyl-CoA-dependent O-acyltransferases catalyze reactions in which fatty acyl-CoAs are joined to acyl acceptors containing free hydroxyl groups to produce neutral lipids. In this report, we characterize a human multifunctional O-acyltransferase (designated MFAT) that belongs to the acyl-CoA:diacylglycerol acyltransfera...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M500168-JLR200
更新日期:2005-11-01 00:00:00
abstract::A method is described for determining the long-chain base content of glycosphingolipids after acid hydrolysis, using the new reagent fluorescamine. The reaction is sensitive and can be used to characterize or measure glycosphingolipids in quantities routinely separated by thin-layer chromatography. ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1974-03-01 00:00:00
abstract::apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipos...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M050567
更新日期:2015-02-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M039206
更新日期:2013-10-01 00:00:00
abstract::Recent findings described the role of CD36-mediated signaling in regulating cellular calcium and the release of various bioactive molecules, including the prostaglandins, neurotransmitters, cholecystokinin, and secretin. Here we document the role of CD36 in the secretion of hepatic VLDL. CD36 deletion resulted in 60% ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M037812
更新日期:2013-11-01 00:00:00
abstract::There is growing evidence of the capacity of vitamin A to regulate the expression of the genetic region that encodes apolipoproteins (apo) A-I, C-III, and A-IV. This region in turn has been proposed to modulate the expression of hyperlipidemia in the commonest genetic form of dyslipidemia, familial combined hyperlipid...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1999-03-01 00:00:00
abstract::The measurement of apolipoprotein B (apoB) in purified lipoproteins by immunological assays is subject to criticism because of denatured epitopes or immunoreactivity differences between purified lipoproteins and standard. Chemical methods have therefore been developed, such as the selective precipitation of apoB follo...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1996-12-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.m100404-jlr200
更新日期:2002-09-01 00:00:00
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journal_title:Journal of lipid research
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doi:
更新日期:2001-07-01 00:00:00
abstract::A synthetic analog of glucocerebroside, N-hexyl-O-glucosyl sphingosine, was found to inhibit the glucosidase in rat spleen that hydrolyzes glucocerebroside. At a concentration of 1 micro m, the analog inhibited the enzyme by 48%. The mode of action appeared to be competitive, probably aided by tight binding of the ami...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1973-03-01 00:00:00
abstract::Geranylgeranoic acid (GGA) has been reported to induce autophagic cell death via upregulation of lipid-induced unfolded protein response in several human hepatoma-derived cell lines, and its 4,5-didehydro derivative has been developed as a preventive agent against second primary hepatoma in clinical trials. We have pr...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M090548
更新日期:2019-03-01 00:00:00
abstract::A new polarographic system for measurement of oxygen consumption in vitro has been constructed to minimize different types of errors. The system was built of polyamide-6, Monax glass, stainless steel, and rubber to diminish oxygen leakage and gas capacitance properties. With these materials the system was gas-tight. N...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1986-09-01 00:00:00
abstract::Lec9 Chinese hamster ovary cells were found previously to be defective in the synthesis of N-linked glycans. This appeared to be the result of a defect in the synthesis of oligosaccharide lipid and lipid phosphate (Rosenwald, Stanley, and Krag. 1989. Mol. Cell. Biol. 9: 914-924). In this study we analyzed the steady s...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::Genetic defects in SAR1B GTPase inhibit chylomicron (CM) trafficking to the Golgi and result in a huge intraenterocyte lipid accumulation with a failure to release CMs and liposoluble vitamins into the blood circulation. The central aim of this study is to test the hypothesis that SAR1B deletion (SAR1B-/- ) disturbs e...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.RA119000119
更新日期:2019-10-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M008359
更新日期:2010-09-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00