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| 7α-hydroxycholesterol |
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| CHEBI:17500 |
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| 7alpha-hydroxycholesterol |
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| The 7α-hydroxy derivative of cholesterol. |
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This entity has been manually annotated by the ChEBI Team.
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CHEBI:20801, CHEBI:12263, CHEBI:2293, CHEBI:89281, CHEBI:13980, CHEBI:58167
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| No supplier information found for this compound. |
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Molfile
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SDF
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more structures >>
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0 0 0 0 0 0 0 0 0 0 0 0 -0.4350 -1.5780 -1.4930 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6770 -2.0040 1.3350 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3630 -3.2430 0.0760 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8430 -2.0270 0.4140 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2690 -2.6470 -1.1600 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1430 -0.4950 -1.9870 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0100 0.3530 0.8230 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0880 2.2100 -0.5380 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8480 2.3830 -0.3290 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1890 1.7810 -1.8690 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5260 -1.2970 -0.3130 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6690 -0.1700 -1.6840 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5760 1.5650 -0.1630 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4340 0.4390 1.2080 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9880 -1.1300 0.0800 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1310 -0.0040 -1.2910 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9820 1.7460 0.2990 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9250 0.8390 2.3500 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9810 -0.5910 2.2610 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6830 1.0160 2.5620 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5470 0.3190 -0.9910 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2140 0.7130 0.6120 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5120 -0.8950 0.3100 H 0 0 0 0 0 0 0 0 0 0 0 0 16 15 1 0 0 0 0 11 10 1 0 0 0 0 12 10 1 0 0 0 0 12 13 1 0 0 0 0 14 15 1 0 0 0 0 14 13 2 0 0 0 0 15 17 1 0 0 0 0 10 9 1 0 0 0 0 13 6 1 0 0 0 0 19 18 1 0 0 0 0 19 20 1 0 0 0 0 17 18 1 0 0 0 0 17 5 1 0 0 0 0 18 2 1 0 0 0 0 9 8 1 0 0 0 0 5 6 1 0 0 0 0 5 4 1 0 0 0 0 20 21 1 0 0 0 0 6 8 1 0 0 0 0 6 7 1 1 0 0 0 21 2 1 0 0 0 0 21 22 1 0 0 0 0 2 3 1 0 0 0 0 2 1 1 1 0 0 0 4 3 1 0 0 0 0 24 22 1 0 0 0 0 24 25 1 0 0 0 0 26 25 1 0 0 0 0 26 27 1 0 0 0 0 28 27 1 0 0 0 0 22 23 1 0 0 0 0 27 29 1 0 0 0 0 1 30 1 0 0 0 0 1 31 1 0 0 0 0 1 32 1 0 0 0 0 3 33 1 0 0 0 0 3 34 1 0 0 0 0 4 35 1 0 0 0 0 4 36 1 0 0 0 0 5 37 1 6 0 0 0 7 38 1 0 0 0 0 7 39 1 0 0 0 0 7 40 1 0 0 0 0 8 41 1 0 0 0 0 8 42 1 0 0 0 0 9 43 1 0 0 0 0 9 44 1 0 0 0 0 10 45 1 6 0 0 0 11 46 1 0 0 0 0 12 47 1 0 0 0 0 12 48 1 0 0 0 0 14 49 1 0 0 0 0 15 50 1 1 0 0 0 16 51 1 0 0 0 0 17 52 1 1 0 0 0 18 53 1 6 0 0 0 19 54 1 0 0 0 0 19 55 1 0 0 0 0 20 56 1 0 0 0 0 20 57 1 0 0 0 0 21 58 1 6 0 0 0 22 59 1 1 0 0 0 23 60 1 0 0 0 0 23 61 1 0 0 0 0 23 62 1 0 0 0 0 24 63 1 0 0 0 0 24 64 1 0 0 0 0 25 65 1 0 0 0 0 25 66 1 0 0 0 0 26 67 1 0 0 0 0 26 68 1 0 0 0 0 27 69 1 0 0 0 0 28 70 1 0 0 0 0 28 71 1 0 0 0 0 28 72 1 0 0 0 0 29 73 1 0 0 0 0 29 74 1 0 0 0 0 29 75 1 0 0 0 0 M END): 26 ms reading 75 atoms ModelSet: haveSymmetry:false haveUnitcells:false haveFractionalCoord:false 1 model in this collection. Use getProperty "modelInfo" or getProperty "auxiliaryInfo" to inspect them. Default Van der Waals type for model set to Babel 75 atoms created ModelSet: not autobonding; use forceAutobond=true to force automatic bond creation Script completed Jmol script terminated
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| 7α-Hydroxycholesterol is a precursor of bile acids, created by cholesterol 7α-hydroxylase (CYP7A1). Its formation is the rate-determining step in bile acid synthesis. |
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Read full article at Wikipedia
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InChI=1S/C27H46O2/c1- 17(2)7-6-8-18(3)21-9-10-22-25-23(12-14-27(21,22)5)26(4)13-11-20(28)15-19(26)16-24(25)29/h16-18,20-25,28-29H,6-15H2,1-5H3/t18-,20+,21-,22+,23+,24-,25+,26+,27-/m1/s1 |
| OYXZMSRRJOYLLO-RVOWOUOISA-N |
| [H][C@@]1(CC[C@@]2([H])[C@]3([H])[C@H](O)C=C4C[C@@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)[C@H](C)CCCC(C)C |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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Found in
blood
(UBERON:0000178).
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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Found in
cerebrospinal fluid
(UBERON:0001359).
See:
PubMed
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mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
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View more via ChEBI Ontology
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(3β,7α)-cholest-5-ene-3,7-diol
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ChemIDplus
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5-cholesten-3β,7α-diol
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MetaCyc
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7-alpha-hydroxycholesterol
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ChemIDplus
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7α-hydroxy-cholesterol
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LIPID MAPS
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7alpha-Hydroxycholesterol
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KEGG COMPOUND
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7α-hydroxycholesterol
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UniProt
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cholest-5-en-3β,7α-diol
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ChemIDplus
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Cholest-5-ene-3beta,7alpha-diol
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KEGG COMPOUND
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566-26-7
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CAS Registry Number
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ChemIDplus
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Lütjohann D, Stellaard F, Björkhem I (2020)
Levels of 7alpha-hydroxycholesterol and/or 7alpha-hydroxy-4-cholest-3-one are the optimal biochemical markers for the evaluation of treatment of cerebrotendinous xanthomatosis.
Journal of neurology 267, 572-573 [PubMed:31781930] | Hausmann J, Keune WJ, Hipgrave Ederveen AL, van Zeijl L, Joosten RP, Perrakis A (2016)
Structural snapshots of the catalytic cycle of the phosphodiesterase Autotaxin.
Journal of structural biology 195, 199-206 [PubMed:27268273]
[show Abstract]
Autotaxin (ATX) is a secreted phosphodiesterase that produces the signalling lipid lysophosphatidic acid (LPA). The bimetallic active site of ATX is structurally related to the alkaline phosphatase superfamily. Here, we present a new crystal structure of ATX in complex with orthovanadate (ATX-VO5), which binds the Oγ nucleophile of Thr209 and adopts a trigonal bipyramidal conformation, following the nucleophile attack onto the substrate. We have now a portfolio of ATX structures we discuss as intermediates of the catalytic mechanism: the new ATX-VO5 structure; a unique structure where the nucleophile Thr209 is phosphorylated (ATX-pThr). Comparing these to a complex with the LPA product (ATX-LPA) and with a complex with a phosphate ion (ATX-PO4), that represent the Michaelis complex of the reaction, we observe movements of Thr209, changes in the relative displacement of the zinc ions, and a water molecule that likely fulfils the second nucleophilic attack. We propose that ATX follows the associative two-step in-line displacement mechanism. | Keune WJ, Hausmann J, Bolier R, Tolenaars D, Kremer A, Heidebrecht T, Joosten RP, Sunkara M, Morris AJ, Matas-Rico E, Moolenaar WH, Oude Elferink RP, Perrakis A (2016)
Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling.
Nature communications 7, 11248 [PubMed:27075612]
[show Abstract]
Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function. We present crystal structures of rat ATX bound to 7α-hydroxycholesterol and the bile salt tauroursodeoxycholate (TUDCA), showing how the tunnel selectively binds steroids. A structure of ATX simultaneously harbouring TUDCA in the tunnel and LPA in the pocket, together with kinetic analysis, reveals that bile salts act as partial non-competitive inhibitors of ATX, thereby attenuating LPA receptor activation. This unexpected interplay between ATX-LPA signalling and select steroids, notably natural bile salts, provides a molecular basis for the emerging association of ATX with disorders associated with increased circulating levels of bile salts. Furthermore, our findings suggest potential clinical implications in the use of steroid drugs. | Kim SM, Kim BY, Lee SA, Eo SK, Yun Y, Kim CD, Kim K (2014)
27-Hydroxycholesterol and 7alpha-hydroxycholesterol trigger a sequence of events leading to migration of CCR5-expressing Th1 lymphocytes.
Toxicology and applied pharmacology 274, 462-470 [PubMed:24370436]
[show Abstract]
Th1 lymphocytes are predominant in atherosclerotic lesions. However, mechanisms involved in the Th1 predominance are unknown. We have investigated the possibility of Th1 lymphocyte recruitment in a cholesterol-rich milieu. A high cholesterol diet resulted in enhanced expression of CCR5 ligands, including CCL3 and CCL4, but not of proatherogenic CXCR3 ligands, in atherosclerotic arteries of ApoE(-/-) mice. 27-Hydroxycholesterol and 7α-hydroxycholesterol, cholesterol oxides (oxysterols) detected in abundance in atherosclerotic lesions, greatly induced the transcription of CCL3 and CCL4 genes in addition to enhancing secretion of corresponding proteins by THP-1 monocytic cells. However, an identical or even higher concentration of cholesterol, 7β-hydroxycholesterol, and 7-ketocholsterol did not influence expression of these chemokines. Conditioned media containing the CCR5 ligands secreted from THP-1 cells induced migration of Jurkat T cells expressing CCR5, a characteristic chemokine receptor of Th1 cells, but not of Jurkat T cells that do not express CCR5. The migration of CCR5-expressing Jurkat T cells was abrogated in the presence of a CCR5-neutralizing antibody. 27-Hydroxycholesterol and 7α-hydroxycholesterol enhanced phosphorylation of Akt. Pharmacological inhibitors of phosphoinositide-3-kinase/Akt pathways blocked transcription as well as secretion of CCL3 and CCL4 in conjunction with attenuated migration of CCR5-expressing Jurkat T cells. This is the first report on the involvement of cholesterol oxides in migration of distinct subtype of T cells. We propose that 27-hydroxycholesterol and 7α-hydroxycholesterol can trigger a sequence of events that leads to recruitment of Th1 lymphocytes and phosphoinositide-3-kinase/Akt pathways play a major role in the process. | Kitano S, Yoshida Y, Kawano K, Hibi N, Niki E (2007)
Oxidative status of human low density lipoprotein isolated by anion-exchange high-performance liquid chromatography--assessment by total hydroxyoctadecadienoic acid, 7-hydroxycholesterol, and 8-iso-prostaglandin F(2alpha).
Analytica chimica acta 585, 86-93 [PubMed:17386651]
[show Abstract]
This study aims to measure the oxidative status of LDL from human plasma (n=26) as assessed by biomarkers for lipid peroxidation, total hydroxyoctadecadienoic acid (tHODE), 7alpha- and 7beta-hydroxycholesterol (t7-OHCh), and 8-iso-prostaglandin F(2alpha) (t8-iso-PGF(2alpha)) after subfractionation of LDL with an anion-exchange HPLC (AE-HPLC). LDL was separated and quantified by AE-HPLC as LDL-1, LDL-2, and LDL-3 in the order of the anionic charge of the LDL particles. The concentrations of tHODE, t7-OHCh, and t8-iso-PGF(2alpha) in both plasma and LDL subfractions were assessed after reduction and saponification. In this method, the free and ester forms of hydroperoxides, ketones, and hydroxides of linoleic acid and cholesterol are measured as tHODE and t7-OHCh, respectively. It was found that tHODE significantly correlated with the proportion of LDL-2 and LDL-3 as well as with the concentration of malondialdehyde-modified LDL in plasma. Further, by the analyses of LDL subfractions, the concentrations of tHODE, t8-iso-PGF(2alpha), and t7-OHCh in LDL-3 were found to be significantly higher than those in LDL-1 and LDL-2. These results clearly indicate that the extent of oxidation increases in the order of LDL-1 | Ferderbar S, Pereira EC, Apolinário E, Bertolami MC, Faludi A, Monte O, Calliari LE, Sales JE, Gagliardi AR, Xavier HT, Abdalla DS (2007)
Cholesterol oxides as biomarkers of oxidative stress in type 1 and type 2 diabetes mellitus.
Diabetes/metabolism research and reviews 23, 35-42 [PubMed:16634125]
[show Abstract]
BackgroundOxidative stress plays an important role in the pathophysiology of diabetes mellitus. The aim of this study was to evaluate the formation of cholesterol oxides (ChOx) as biomarkers of oxidative stress in subjects with impaired glucose tolerance (IGT) and diabetes.MethodsBlood plasma levels of cholesterol oxidation products were determined in the following groups: type 1 diabetes mellitus (DM1), type 2 diabetes (DM2), impaired glucose tolerance (IGT), children without diabetes (C1) and adults without diabetes (C2). The serum levels of cholest-5-ene-3alpha,7alpha-diol (7alpha-hydroxycholesterol, 7alpha-OH), cholest-5-ene-3beta,7beta-diol (7beta-hydroxycholesterol, 7beta-OH), 3beta-hydroxycholest-5-7-one (7-ketocholesterol, 7-K), 5alpha-cholestane-3beta,5,6beta-triol (cholestanetriol), 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol (cholesterol-5alpha,6alpha-epoxide,), 5,6beta-epoxy-5beta-cholestan-3beta-ol (cholesterol-5beta,6beta-epoxide) and cholest-5-eno-3beta,25-diol (25-hydroxycholesterol, 25-OH) (trivial name and abbreviations indicated in parentheses) were quantified by gas chromatography using flame ionization detection.ResultsThe levels of total ChOx were elevated in the DM1 and DM2 groups compared to age-matched subjects without diabetes (p < 0.05). The concentrations of 7beta-hydroxycholesterol, cholesterol-alpha-epoxide and cholesterol-beta-epoxide were higher in the blood plasma of subjects in the DM2 group than in the blood plasma of subjects in the C2 and IGT groups (p < 0.05). Treatment of type 2 diabetic patients with oral hypoglycemic drugs associated with insulin resulted in lower concentrations of nitrotyrosine in the blood plasma without significant changes in the concentrations of glucose and glycated hemoglobin. Moreover, combination with statins in both treatments decreased the concentrations of ChOx.ConclusionsChOx are suitable biomarkers of oxidative stress and may be useful in clinical studies to follow drug effects on lipid oxidative modifications in diabetic patients. | Erridge C, Webb DJ, Spickett CM (2007)
25-Hydroxycholesterol, 7beta-hydroxycholesterol and 7-ketocholesterol upregulate interleukin-8 expression independently of Toll-like receptor 1, 2, 4 or 6 signalling in human macrophages.
Free radical research 41, 260-266 [PubMed:17364953]
[show Abstract]
Recent studies have shown that Toll-like receptor (TLR)- signalling contributes significantly to the inflammatory events of atherosclerosis. As products of cholesterol oxidation (oxysterols) accumulate within atherosclerotic plaque and have been proposed to contribute to inflammatory signalling in the diseased artery, we investigated the potential of 7-ketocholesterol (7-KC), 7beta-hydroxycholesterol (7beta-HC) and 25-hydroxycholesterol (25-HC) to stimulate inflammatory signalling via the lipid-recognising TLRs 1, 2, 4 and 6. Each oxysterol stimulated secretion of the inflammatory chemokine interleukin-8 (IL-8), but not IkappaBalpha degradation or tumour necrosis factor-alpha release from monocytic THP-1 cells. Transfection of TLR-deficient HEK-293 cells with TLRs 1, 2, 4 or 6 did not increase sensitivity to the tested oxysterols. Moreover, blockade of TLR2 or TLR4 with specific inhibitors did not reduce 25-hydroxycholesterol (25-HC) induced IL-8 release from THP-1 cells. We conclude that although the oxysterols examined in this study may contribute to increased expression of certain inflammatory genes, this occurs by mechanisms independent of TLR signalling. | Prunet C, Petit JM, Ecarnot-Laubriet A, Athias A, Miguet-Alfonsi C, Rohmer JF, Steinmetz E, Néel D, Gambert P, Lizard G (2006)
High circulating levels of 7beta- and 7alpha-hydroxycholesterol and presence of apoptotic and oxidative markers in arterial lesions of normocholesterolemic atherosclerotic patients undergoing endarterectomy.
Pathologie-biologie 54, 22-32 [PubMed:16376175]
[show Abstract]
In previous investigations, we found that 7beta-hydroxycholesterol had potent pro-apoptotic, and pro-oxidative properties. So, we asked whether the circulating level of this oxysterol was enhanced in atherosclerotic patients undergoing endarterectomy of the superficial femoral artery. To this end, 7beta-hydroxycholesterol serum concentrations were determined and compared with common lipid parameters in atherosclerotic patients, and in healthy subjects. 7alpha-hydroxycholesterol was simultaneously measured to evaluate the reliability of the method used for oxysterol analysis. On normal and atherosclerotic arterial fragments from patients, markers of oxidation (4-hydroxynonenal (4-HNE) adducts), and apoptosis (activated caspase-3; condensed/fragmented nuclei) were studied. Interestingly, high serum concentrations of 7beta- and 7alpha-hydroxycholesterol were found in normocholesterolemic atherosclerotic patients. However, in statin-treated patients, the circulating levels of 7beta- and 7alpha-hydroxycholesterol tend towards normal values. Therefore, 7beta- as well as 7alpha-hydroxycholesterol could be more appropriate markers of lipid metabolism disorders than cholesterol or LDL in normocholesterolemic patients with atherosclerosis of the lower limbs, and statins could normalize their serum concentrations. At the arterial level, apoptotic cells were mainly identified in low grade lesions and no statin effects were found on oxidation and apoptosis. | Maeda Y, Shinohara A, Koshimoto C, Chijiiwa K (2006)
Species differences among various rodents in the conversion of 7alpha-hydroxycholesterol in liver microsomes.
Steroids 71, 329-333 [PubMed:16455124]
[show Abstract]
Our previous study demonstrated that there are species differences among vertebrates in their conversion of 7alpha-hydroxycholesterol (7HC) to 7-ketocholesterol (7KC). To examine this further, we investigated the differences in the products of 7alpha-hydroxycholesterol in various species of male muroid rodents. Adult male Syrian hamsters (Mesocricetus auratus), dwarf hamsters (Phodopus rovolovskii), Djungarian hamsters (Phodopus sungorus), Chinese hamsters (Cricetulus griseus), rat-like hamsters (Tscherskia triton), and hispid cotton rats (Sigmodon hispidus) were used. Microsomal fractions were prepared from their livers, and the activities of the enzymes that participate in the dehydrogenation of 7alpha-hydroxycholesterol were determined by measuring the products using high-performance liquid chromatography. 7alpha-hydroxycholesterol was converted to both 7alpha-hydroxy-4-cholesten-3-one (7HCO) and 7-ketocholesterol in all of the hamsters tested. However, in the rat-like hamster and the hispid cotton rat, 7alpha-hydroxycholesterol was converted mostly to 7alpha-hydroxy-4-cholesten-3-one, as also observed in the rat (Rattus norvegicus). The results suggest that microsomal enzyme activity in the conversion of 7alpha-hydroxycholesterol to 7-ketocholesterol varies considerably, even within the subfamily Cricetinae and the family Muridae. | Leoni V, Lütjohann D, Masterman T (2005)
Levels of 7-oxocholesterol in cerebrospinal fluid are more than one thousand times lower than reported in multiple sclerosis.
Journal of lipid research 46, 191-195 [PubMed:15576852]
[show Abstract]
In a recent publication [Diestel, A., O. Aktas, D. Hackel, I. Hake, S. Meier, C. S. Raine, R. Nitsch, F. Zipp, and O. Ullrich. 2003. Activation of microglial poly (ADP-ribose)-polymerase-1 by cholesterol breakdown products during neuroinflammation: a link between demyelination and neuronal damage. J. Exp. Med. 198: 1729-1740], extremely high levels of 7-oxocholesterol were reported in cerebrospinal fluid (CSF) of 11 patients with multiple sclerosis (MS) [7.4 +/- 0.3 mg/l (mean +/- SEM)]. The corresponding level of 12 subjects with other kinds of neurological diseases was reported to be 0.5 +/- 0.1 mg/l. Such high levels of 7-oxocholesterol were found to cause neuronal damage of living brain tissues. Using a highly accurate method for an assay of 7-oxocholesterol based on isotope dilution-mass spectrometry and anaerobic conditions during workup, we found that the level of 7-oxocholesterol in CSF from 29 Swedish patients with MS was only 1.2 microg/l (median, ranging from 0.4 to 4.6 microg/l), less than 1/1,000 th of the previously reported level. The level of 7-oxocholesterol in CSF from 24 Swedish control patients was 0.9 microg/l (0.3-2.3 microg/l), slightly but significantly lower than the CSF level in MS patients (P=0.002). In vitro-induced lipid peroxidation of the endogenous cholesterol in CSF increased the level of 7-oxygenated cholesterol metabolites, particularly 7-oxocholesterol, up to approximately 0.3 mg/l. These results are discussed in relation to the fact that 7-oxygenated steroids are easily artificially formed by autoxidation of cholesterol during workup procedures and analysis of sterols and oxysterols from biological samples. | Nakamura K, Chijiiwa K, Kuroki S, Naito T, Mizuta A, Tanaka M (2003)
Serum 7alpha-hydroxycholesterol levels during liver regeneration after hepatectomy in humans.
Hepato-gastroenterology 50, 1593-1597 [PubMed:14571793]
[show Abstract]
Background/aimsChanges in bile acid synthesis during liver regeneration after hepatectomy is little known in humans. Since it has been reported that the serum 7 alpha-hydroxycholesterol levels reflect the hepatic bile acid synthesis and that the determination of bile acid synthesis is useful to assess the liver regeneration rate, we determined the serum 7 alpha-hydroxycholesterol level during liver regeneration after hepatectomy in clinical patients.MethodologyThe serum 7 alpha-hydroxycholesterol levels were determined by gas-liquid chromatography-mass spectrometry-selected ion monitoring method before and on days 1, 3, 5, 7, 14 and 21 after hepatectomy in twenty consecutive patients.ResultsThe 7 alpha-hydroxycholesterol levels became lower between days 1 and 7, were increased on day 14, and then decreased on day 21 after hepatectomy. The patients with preoperative external biliary drainage showed a higher serum 7 alpha-hydroxycholesterol level than those without biliary drainage before hepatectomy. The former showed lower serum 7 alpha-hydroxycholesterol levels than the latter throughout the 21 days after hepatectomy. In patients whose liver resection rate was more than 50%, the serum 7 alpha-hydroxycholesterol levels were kept lower until 21 days after hepatectomy compared with those whose liver was excised less than 50%.ConclusionsIt is concluded that the patients who had preoperative biliary drainage or major hepatic resection seem to have less hepatic reserve capacity for bile acid synthesis after hepatectomy. | Kuroki S, Naito T, Chijiiwa K, Tanaka M (1999)
Effects of cholestyramine on hepatic cholesterol 7alpha-hydroxylase and serum 7alpha-hydroxycholesterol in the hamster.
Lipids 34, 817-823 [PubMed:10529092]
[show Abstract]
Cholestyramine increases activities of hepatic cholesterol 7alpha-hydroxylase and serum levels of 7alpha-hydroxycholesterol. To examine if serum 7alpha-hydroxycholesterol levels parallel with enzyme activity, 0, 0.5, 1, 2, 4, and 10% of cholestyramine was administered to female golden Syrian hamsters for 28 d in the dose-dependent study, and 2% cholestyramine for 0, 1, 3, 7, 14, 21, and 28 d in the time-dependent study. In the dose-dependent study, hepatic and serum cholesterol levels were significantly decreased dose-dependently when more than 0.5% of cholestyramine was fed for 28 d. Cholestyramine increased the cholesterol 7alpha-hydroxylase activity in a dose-dependent manner, while the serum 7alpha-hydroxycholesterol level was essentially unchanged. No correlation was found between the serum level and the hepatic enzyme activity. In the time-dependent study, hepatic and serum cholesterol levels markedly decreased when 2% cholestyramine was fed for longer than 3 d. The serum triglyceride level increased significantly for the first 7 d and then decreased. Cholesterol 7alpha-hydroxylase activity increased significantly as early as day 1, reached maximum activity level on day 7, and then kept the significantly high values until day 28. The serum 7alpha-hydroxycholesterol level significantly increased for the first 7 d and decreased to the pretreatment level thereafter. 7Alpha-hydroxycholesterol levels significantly correlated with serum cholesterol and triglyceride levels. We conclude that the serum 7alpha-hydroxycholesterol level does not always reflect the activity of hepatic cholesterol 7alpha-hydroxylase, when cholesterol metabolism is severely disturbed by cholestyramine. | Saisho Y, Shimada C, Umeda T (1998)
Determination of 7alpha-hydroxycholesterol in dog plasma by high-performance liquid chromatography with fluorescence detection.
Analytical biochemistry 265, 361-367 [PubMed:9882415]
[show Abstract]
A new method was developed for the determination of 7alpha-hydroxycholesterol (7-HC) in dog plasma by means of high-performance liquid chromatography (HPLC) with fluorescence detection. 7-HC extracted with organic solvent from plasma was purified with Bond Elut 2OH and converted to a sensitive fluorescent derivative containing double coumarin groups at the C-3 and C-7 positions of the steroid nucleus with 7-methoxycoumarin-3-carbonyl azide. After removal of the excess reagent with Bond Elut NH2, the 7-HC derivative was separated by reverse-phase HPLC method. The detection limit of the authentic 7-HC-3,7-coumarin derivative was 4 pg (S/N = 5), approximately four times less than that of the 7-HC-3-anthroyl derivative yielded by reaction of 7-HC with 1-anthroylcyanide. The newly developed method was used to investigate the effects of consecutive oral administrations of cholestyramine (CA) on 7-HC levels in dog plasma. The plasma 7-HC levels of the CA-treated group were two times greater than those of the control group. | Song W, Chen J, Dean WL, Redinger RN, Prough RA (1998)
Purification and characterization of hamster liver microsomal 7alpha-hydroxycholesterol dehydrogenase. Similarity to type I 11beta-hydroxysteroid dehydrogenase.
The Journal of biological chemistry 273, 16223-16228 [PubMed:9632680]
[show Abstract]
While studying the bile acid synthetic pathway of hamsters, we discovered an NADP+-dependent liver microsomal 7alpha-hydroxycholesterol dehydrogenase (7alpha-HCD) activity that was not observed in rat liver microsomal fractions. The hamster liver microsomal 7alpha-HCD was purified to homogeneity using 2', 5'-ADP and cholic acid-agarose affinity chromatography. 7alpha-HCD displayed a molecular weight of approximately 34,000 on SDS-polyacrylamide gel electrophoresis; it is an intrinsic membrane protein of the hamster liver endoplasmic reticulum and exists as a multimeric aggregate in pure form. Partial N-terminal amino acid sequence analysis showed that 7alpha-HCD had high sequence similarity to human 11beta-hydroxysteroid dehydrogenase (11beta-HSD; 24/30 amino acid identity). The Km values for corticosterone and 7alpha-hydroxycholesterol were 1.2 and 1.9 microM, respectively, for purified 7alpha-HCD; both reactions displayed identical Vmax values (approximately 170 nmol/min/mg of protein). The IC50 of carbenoxolone, a competitive inhibitor of 11beta-HSD, was 75 nM for 7alpha-hydroxycholesterol dehydrogenation and 210 nM for corticosterone dehydrogenation. The tissue-specific expression in hamster was as follows: adrenal >/= liver > kidney > testis >> brain > lung. Microsomal 7alpha-HCD is uniquely expressed in hamster liver and to some extent in human liver but not in rat liver. Western blot analysis with two antibodies elicited against an N-terminal peptide of the human 11beta-HSD and purified hamster liver 7alpha-HCD, respectively, suggested the presence of multiple forms of 7alpha-HCD in hamster liver, most likely due to the existence of a family of 11beta-HSD proteins. Since 7-oxocholesterol is a potent inhibitor of cholesterol 7alpha-hydroxylase, alternative mechanisms for regulation of bile acid synthesis may exist in human and hamster liver due to production of this metabolite and its potential as an oxysterol. | Kuroki S, Okamoto S, Naito T, Oda H, Nagase S, Sakai H, Nawata H, Yamashita H, Chijiiwa K, Tanaka M (1995)
Serum 7 alpha-hydroxycholesterol as a new parameter of liver function in patients with chronic liver diseases.
Hepatology (Baltimore, Md.) 22, 1182-1187 [PubMed:7557870]
[show Abstract]
To examine bile acid synthesis in chronic liver diseases, serum total 7 alpha-hydroxycholesterol level was measured by gas-liquid chromatography-mass spectrometry in patients with cirrhosis (n = 23), patients with chronic hepatitis (n = 21), and control subjects (n = 18). The serum 7 alpha-hydroxycholesterol levels were significantly lower in patients with cirrhosis than the controls (78 +/- 59 pmol/mL vs. 237 +/- 97 pmol/mL; mean +/- SD). However, in patients with chronic hepatitis, the level was fully retained (262 +/- 102 pmol/mL). Serum 7 alpha-hydroxycholesterol levels of 17 patients with cirrhosis classified as Child B and C ranged from 33 to 69 pmol/mL, and all were less than the normal range (between 104 and 466 pmol/mL), however, those levels of some patients classified as Child A were within the normal range. Serum 7 alpha-hydroxycholesterol levels significantly correlated with serum albumin, cholinesterase, total bile acid, direct bilirubin, alkaline phosphatase, indocyanine green (ICG) retention rate, hepaplastin test, and lecithin-cholesterol acyltransferase activities. We conclude that bile acid synthesis is well preserved in patients with chronic hepatitis and that it is decreased in most patients with cirrhosis. Serum 7 alpha-hydroxycholesterol may be a new parameter of liver function testing to assess hepatic bile acid synthesis in patients with chronic liver diseases. | Hahn C, Reichel C, von Bergmann K (1995)
Serum concentration of 7 alpha-hydroxycholesterol as an indicator of bile acid synthesis in humans.
Journal of lipid research 36, 2059-2066 [PubMed:8558093]
[show Abstract]
The serum concentration of 7 alpha-hydroxycholesterol as an indicator of total bile acid synthesis was investigated under different experimental conditions in humans. 7 alpha-Hydroxycholesterol was measured by gas-liquid chromatography-mass spectrometry, using [2H7]7 alpha-hydroxycholesterol and/or 5 alpha-cholestane-3 beta, 6 beta-diol as internal standards, and bile acid synthesis was estimated by the fecal balance method. Intraindividual variation was small when the concentration of 7 alpha-hydroxycholesterol was determined twice in the same subject 2 days to 11 months apart (7.3 +/- 6.5%, n = 52). In patients with advanced cirrhosis of the liver (n = 22) 7 alpha-hydroxycholesterol was 3.4-fold lower (22 ng/ml +/- 8) compared to matched controls (75 ng/ml +/- 19). Administration of cholestyramine (4 g b.i.d.) for 14 days increased 7 alpha-hydroxycholesterol concentration in five healthy volunteers from 40 +/- 11 ng/ml to 181 +/- 95 ng/ml (P = 0.02) and fecal excretion of acidic sterols from 254 +/- 60 mg/d to 1336 +/- 344 mg/d (P < 0.01). Although a significant correlation was found between 7 alpha-hydroxycholesterol in serum and bile acid synthesis in patients with hypercholesterolemia (r = 0.847, P < 0.001, n = 17), it was impossible to accurately determine bile acid synthesis from the serum levels of 7 alpha-hydroxycholesterol. Thus, determination of 7 alpha-hydroxycholesterol concentrations in serum can be used to assess changes in bile acid synthesis rates over short and long term periods under various experimental conditions, but not to calculate bile acid synthesis correctly. |
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