cholesterol-alpha-oxide has been researched along with cholestane-3-5-6-triol* in 14 studies
1 review(s) available for cholesterol-alpha-oxide and cholestane-3-5-6-triol
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Cholesterol epoxide hydrolase and cancer.
Cholesterol epoxide hydrolase (ChEH) catalyzes the hydration of cholesterol-5,6-epoxides (5,6-EC) into cholestane-3β,5α,6β-triol. ChEH is a hetero-oligomeric complex called the anti-estrogen binding site (AEBS) comprising 3β-hydroxysterol-Δ(8)-Δ(7)-isomerase (D8D7I) and 3β-hydroxysterol-Δ(7)-reductase (DHCR7). D8D7I and DHCR7 regulate cholesterol biosynthesis, fetal development and growth, tumor cell differentiation and death. The un-reactivity of 5,6-EC toward nucleophiles has recently been demonstrated indicating that 5,6-EC are not alkylating and carcinogenic agents as first postulated. Here we discuss recent advances in the molecular characterization of ChEH, its potential role in cancer progression and resistance as well as the interest of inhibiting ChEH and to accumulate 5,6-EC which may contribute to the anti-tumor and chemopreventive action of ChEH inhibitors used in the clinic such as tamoxifen. Topics: Animals; Antineoplastic Agents, Hormonal; Cholestanols; Cholesterol; Disease Progression; Drug Resistance, Neoplasm; Epoxide Hydrolases; Humans; Neoplasms; Tamoxifen | 2012 |
13 other study(ies) available for cholesterol-alpha-oxide and cholestane-3-5-6-triol
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Cholesterol oxides as biomarkers of oxidative stress in type 1 and type 2 diabetes mellitus.
Oxidative 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.. Blood 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.. The 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.. ChOx are suitable biomarkers of oxidative stress and may be useful in clinical studies to follow drug effects on lipid oxidative modifications in diabetic patients. Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Child; Cholestanols; Cholesterol; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Humans; Hydroxycholesterols; Hypoglycemic Agents; Insulin; Ketocholesterols; Male; Middle Aged; Oxidative Stress | 2007 |
Cholesterol-3-beta, 5-alpha, 6-beta-triol induced genotoxicity through reactive oxygen species formation.
The mutagenicity of oxysterols, cholesterol-3beta,5alpha,6beta-triol (alpha-Triol), 7-keto-cholesterol (7-Keto) and cholesterol-5alpha,6alpha-epoxide (alpha-Epox) were examined by the Ames method and chromosome aberration test in this study. Only alpha-Triol concentration-dependently caused an increase of bacterial revertants in the absence of metabolic activating enzymes (S9), but not 7-keto and alpha-Epox. The mutagenic effect of alpha-Triol was reduced by the addition of S9. On the other hand, although alpha-Triol significantly induced chromosome aberration in CHO-K1 cells with and without S9. However, the addition of S9 reduced the degree of abnormal structure chromosome compared to without S9 mix. Catalase and superoxide dismutase (SOD) inhibited alpha-Triol induced increase of revertants in Salmonella typhimurium and chromosome aberration frequency in CHO cells, suggesting that reactive oxygen species (ROS) might be involved in the genotoxic effect of alpha-Triol. Treatment with alpha-Triol increased the ROS production in CHO cells, which could be attenuated by catalase and SOD. Results in this study suggested, for the first time that alpha-Triol, causes genotoxic effect in an ROS-dependent manner. Topics: Animals; Catalase; CHO Cells; Cholestanols; Cholesterol; Chromosome Aberrations; Cricetinae; Cricetulus; DNA Damage; Ketocholesterols; Mutagenicity Tests; Reactive Oxygen Species; Salmonella; Superoxide Dismutase | 2005 |
Interactive effects of increased intake of saturated fat and cholesterol on atherosclerosis in the Japanese quail (Coturnix japonica).
Increasing the energy value of diets with dietary fat, particularly fats rich in saturated fatty acids, can result in the elevation of plasma total and lipoprotein cholesterol. In the present study, experimental diets were designed to examine the effects of increasing the energy content of diets with a saturated fat source and cholesterol in a non-purified diet on hyperlipoproteinaemia and aortic plaque composition in the atherosclerosis-susceptible Japanese quail (Coturnix japonica) model of human atherosclerosis. Commercial poultry diets containing two levels (i.e. 60 or 120 g/kg) of beef tallow as the primary source of saturated fat were balanced for endogenous cholesterol or supplemented with cholesterol (i.e. 0.5 or 5.0 g/kg) and fed to quail for 9 weeks to examine the effects on whole plasma, lipoprotein and aortic plaque lipid composition in relation to aortic plaque formation. Hypercholesterolaemia (P < 0.001) was confirmed in birds fed on high-cholesterol (HC) diets only. An interaction (P = 0.05) between dietary cholesterol and fat intake level was observed for plasma triacylglycerols (TG) and was specific to changes observed in VLDL composition. Diet-induced changes in lipoprotein total cholesterol, TG and phospholipid composition were greatest in the portomicron and VLDL fractions in birds fed on atherogenic diets. Hyperlipoproteinaemia induced by the 60 g/kg added beef tallow-HC diet resulted in significant (P < 0.001) aortic plaque deposition, which was further enhanced in birds fed on the 120 g/kg beef tallow-HC diet. Quail fed on 120 g/kg beef tallow-HC diets exhibited the most severe aortic plaque formation, with marked increases in aortic tissue cholesterol content and quantifiable amounts of several cholesterol oxides (5,6 alpha-epoxy-5 alpha-cholesterol, 7 beta-hydroxycholesterol, cholestanetriol, 7-ketocholesterol and 25-hydroxycholesterol). In summary, hyperlipoproteinaemia associated with HC diets with a greater proportion of energy from saturated fat produced a combined effect in altering plasma and lipoprotein lipid composition as well as aortic tissue cholesterol and cholesterol oxide content in the Japanese quail. Topics: Analysis of Variance; Animals; Aorta; Arteriosclerosis; Bird Diseases; Cholestanols; Cholesterol; Cholesterol, Dietary; Coturnix; Dietary Fats; Disease Models, Animal; Energy Intake; Hydroxycholesterols; Hypolipidemic Agents; Ketocholesterols; Lipids; Lipoproteins; Male; Regression Analysis | 1998 |
Inhibitory effect of cholesterol oxides on low density lipoprotein receptor gene expression.
The effects of the cholesterol oxides on low density lipoprotein receptor (LDLR) gene expression were investigated. Cultured rabbit aortic smooth muscle cells were incubated with 1, 2, and 5 micrograms/ml culture medium concentrations of pure cholesterol, 25-hydroxycholesterol (25-OH), 7-ketocholesterol (7-keto), cholestane-3 beta, 5 alpha, 6 beta-triol (triol) and cholesterol-5 alpha, 6 alpha-epoxide (epoxide) for 12 hours and with vehicle only as control. Total mRNAs were extracted and electrophoresed. Northern blot hybridization analyses were performed. The results showed mRNA expressions of LDLR gene were inhibited to 16.1 +/- 4.4%, 33.8 +/- 0.6%, 42.8 +/- 1.8% and 46.9 +/- 3.9% of control by 25-OH, 7-keto, epoxide and triol respectively. Pure cholesterol showed only minimal inhibition. The inhibitions were time dependent. Although cholesterol oxides have been shown to alter many membrane-related functions and the LDLR domain are located in the cell membrane. The findings of this study suggested that the cholesterol oxides exerted their repressive actions on LDLR function primarily by down-regulating LDLR gene expression rather than directly upon cell membrane. Topics: Animals; Blotting, Northern; Cells, Cultured; Cholestanols; Cholesterol; Gene Expression Regulation; Hydroxycholesterols; Ketocholesterols; Muscle, Smooth, Vascular; Rabbits; Receptors, Lipoprotein; RNA, Messenger | 1996 |
Oxysterols, cholesterol biosynthesis, and vascular endothelial cell monolayer barrier function.
A spectrum of cholesterol oxidation derivatives (oxysterols) is generated in food products exposed to heat or radiation in the presence of oxygen. One of these derivatives (cholestan-3 beta,5 alpha,6 beta-triol) was shown to compromise the selective barrier function of cultured vascular endothelial cell monolayers, an action that may initiate atherosclerotic lesion formation. This study sought to investigate the relationship of cholesterol synthesis inhibition by several naturally occurring oxysterols to depression of vascular endothelial cell monolayer barrier function, determined as an increase in albumin transfer across cultured endothelial monolayers. All oxysterols tested caused a variable time- and dose-dependent elevation in trans-endothelial albumin transfer, and they were also able to inhibit cholesterol biosynthesis to varying degrees. Pure cholesterol was without effect on both counts. The correlation between the increase in albumin transfer related to oxysterol exposure and the ability of oxysterols to suppress cholesterol biosynthesis was, however, poor. Moreover, mevinolin, a water-soluble competitive inhibitor of cholesterol synthesis, reduced the rate of cholesterol synthesis to 0.9% of control but did not significantly increase albumin transfer. Cholestan-3 beta,5 alpha,6 beta-triol caused a 660% elevation in albumin transfer while cholesterol synthesis remained at 11% of control. We conclude that changes in endothelial barrier function caused by exposure to the oxysterols examined, but not pure cholesterol, are probably related to factors other than the well-known action of cholesterol biosynthesis inhibition. These findings may have implications in the development of atherosclerosis. Topics: Animals; Biological Transport; Cell Membrane Permeability; Cholestanes; Cholestanols; Cholesterol; Dehydrocholesterols; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium; Hydroxycholesterols; Hypolipidemic Agents; In Vitro Techniques; Ketocholesterols; Lovastatin; Serum Albumin; Swine; Time Factors | 1991 |
Uptake, metabolism, and cytotoxicity of isomeric cholesterol-5,6-epoxides in rabbit aortic endothelial cells.
The isomeric cholesterol-5,6-epoxides represent two common cholesterol autoxidation products and along with their principal metabolic product, 3 beta,5 alpha,6 beta-cholestane triol, are purportedly angiotoxic. The uptake and cytotoxic action of these compounds was examined in cultured rabbit aortic endothelial cells emphasizing mechanisms of uptake and metabolic fate. The isomeric cholesterol epoxides are incorporated with equal facility and in a dose-dependent manner. The pattern of uptake, which is markedly influenced by media serum concentration and by temperature, suggests that these compounds are partly incorporated through association with serum lipoproteins. After incorporation, both epoxide isomers are rapidly converted to cholestane triol which readily exits the cells. Cholestane triol is further metabolized to an ester-type product representing up to 10% of the added cholesterol epoxides by 24 h of incubation. The order of cytotoxic potency of these cholesterol oxides is: cholestane triol greater than cholesterol-beta-epoxide greater than cholesterol-alpha-epoxide, with LD50 concentrations ranging from 23 to greater than 150 microM in confluent cells. Cholestane triol and cholesterol-beta-epoxide are twice as cytotoxic to subconfluent cells as compared to confluent cells, whereas cholesterol-alpha-epoxide is essentially equitoxic to confluent and subconfluent cells. Cholesterol epoxide cytotoxicity is significantly reduced by treatments in the absence of serum in accord with substantial reduction in uptake when incubations are performed in serum-free media. Our findings show that these cytotoxic cholesterol oxides are incorporated by endothelial cells through a combination of receptor-mediated and nonspecific or passive mechanisms; however, the efficacy of uptake and resulting toxicity is substantially influenced by serum lipoproteins. Topics: Animals; Aorta; Cell Survival; Cells, Cultured; Cholestanols; Cholesterol; Endothelium, Vascular; Hypolipidemic Agents; Isomerism; Kinetics; Rabbits; Temperature; Ultracentrifugation | 1991 |
Influence of cholesterol oxides on endocytosis of cultured endothelial and smooth muscle cells.
Human umbilical vein endothelial cells and rabbit aortic smooth muscle cells in culture were incubated for intervals up to 24 hrs with varying concentrations of cholesterol, 7-ketocholesterol, 25-hydroxycholesterol, cholestane-3 beta,5 alpha,6 beta-triol or cholesterol-5 alpha, 6 beta-epoxide. Endocytosis, as measured by uptake of horseradish peroxidase (HRP), was inhibited in a dose and time dependent manner in both endothelial and smooth muscle cell cultures by cholestane-3 beta,5 alpha,6 beta-triol and 25-hydroxycholesterol. Inhibition by 7-ketocholesterol in endothelial cells occurred only at higher concentrations, and cholesterol and cholesterol epoxide showed no significant inhibitory effects. The viability of the cells exposed to the cholesterol oxides at the concentrations that inhibited the uptake of HRP was not changed. Cholesterol oxides induce functional endothelial injury, not morphologically apparent, which may be involved in atherogenesis. Topics: Animals; Aorta; Cells, Cultured; Cholestanols; Cholesterol; Endocytosis; Endothelium, Vascular; Horseradish Peroxidase; Humans; Hydroxycholesterols; Hypolipidemic Agents; Ketocholesterols; Kinetics; Muscle, Smooth, Vascular; Rabbits; Umbilical Veins | 1990 |
Effect of cholesterol epoxides on the inhibition of intercellular communication and on mutation induction in Chinese hamster V79 cells.
Cholesterol, cholesterol-5 alpha, 6 alpha-epoxide, cholesterol-5 beta, 6 beta-epoxide and cholestane-3 beta,5 alpha,6 beta-triol were tested for their ability to induce mutations at the Na+/K+-ATPase loci of the Chinese hamster V79 cells. None of these compounds induced ouabain-resistant mutations compared to the background mutation frequency in the control cells. These compounds were further tested for their ability to inhibit intercellular communication, using the Chinese hamster V79 cell metabolic cooperation assay. The diastereomeric epoxides and cholestane-triol, but not cholesterol, were found to be inhibitors of intercellular communication in a manner similar to other known tumor promoters. Topics: Animals; Cell Communication; Cell Line; Cholestanols; Cholesterol; Cricetinae; Cricetulus; Depression, Chemical; Fibroblasts; Intercellular Junctions; Lung; Male; Methylnitronitrosoguanidine; Mutagenicity Tests; Sodium-Potassium-Exchanging ATPase | 1988 |
Assay of unesterified cholesterol-5,6-epoxide in human serum by isotope dilution mass spectrometry. Levels in the healthy state and in hyperlipoproteinemia.
Accurate methods based on isotope dilution-mass spectrometry were developed for assay of free cholesterol-5,6-epoxide (sum of 5 alpha,6 alpha- and 5 beta,6 beta-epimer) and cholestane-3 beta,5 alpha,6 beta-triol in human serum. In all serum samples tested, the level of cholesterol epoxides was well above the detection limit (about 10 ng/ml) whereas the level of cholestane-3 beta,5 alpha,6 beta-triol was below or near the detection limit in most cases. Immediate addition of antioxidant was found to be necessary in order to obtain reproducible results in the serum analyses, and prolonged storage of frozen samples had to be avoided. The level of cholesterol epoxide in healthy subjects 23-35 years of age ranged from 67 ng/ml to 293 ng/ml (mean 131 ng/ml, n = 9). There was a tendency to higher levels with increasing age, but there was no correlation to serum cholesterol. In marked contrast to results previously reported with a less accurate method, patients with various forms of hyperlipoproteinemia did not have increased levels of cholesterol epoxide. On the contrary, many of these patients had levels lower than normal. Topics: Cholestanols; Cholesterol; Gas Chromatography-Mass Spectrometry; Humans; Hyperlipoproteinemias; Hypolipidemic Agents; Mass Spectrometry; Reference Values; Triglycerides | 1988 |
Analysis of cholesterol, cholesterol-5,6-epoxides and cholestane-3 beta,5 alpha,6 beta-triol in nipple aspirates of human breast fluid by gas chromatography/mass spectrometry.
A method has been developed for the quantitative determination of cholesterol and three of its major oxidative metabolites (the 5 alpha,6 alpha-epoxide, the 3 beta,5 alpha,6 beta-triol, and the 5 beta,6 beta-epoxide) in a single sample of human breast fluid (2-50 microliters), using gas chromatography/mass spectrometry with selected ion monitoring. High specificity and reliable quantification is achieved by the use of the inverse stable isotope dilution method, employing deuterium-labeled variants of the compounds as internal standards. Topics: Adult; Aged; Body Fluids; Breast; Cholestanols; Cholesterol; Female; Gas Chromatography-Mass Spectrometry; Humans; Middle Aged; Nipples | 1987 |
Connective tissue responses to oxysterols.
We studied the effect of sterols and oxidized sterols on promoting tissue inflammation and necrosis, and on causing cell death in tissue culture. The cells studied were mouse fibroblasts and macrophages, and pig vascular smooth muscle. The lipid preparations were dibromide-purified cholesterol, air-oxidized cholesterol, 25-hydroxycholesterol, cholesterol-5alpha, 6 beta-epoxide and cholestane 3 beta, 5 alpha, 6 beta-triol. Of these, the triol was most active in its cytopathic effect on cells in culture, in size of granuloma formation and in producing necrosis. The epoxide, 25-hydroxycholesterol and air-oxidized cholesterol produced rather less effect on tissues and cultures than the triol, but more than purified cholesterol and the control. The results are considered in relation to the presence of oxysterols in stored foodstuffs and their possible presence over the surface of cholesterol crystals in the tissues. Topics: Animals; Cell Survival; Cells, Cultured; Cholestanols; Cholesterol; Connective Tissue Cells; Fibroblasts; Hydroxycholesterols; Hypolipidemic Agents; Macrophages; Mice; Muscle, Smooth, Vascular; Necrosis; Rats; Sterols; Swine | 1982 |
Cholesterol diet increases plasma and liver concentrations of cholesterol epoxides and cholestanetriol.
Cholesterol alpha-epoxide (5, 6 alpha-epoxy-5-alpha-cholestan-3 beta-ol), cholesterol beta-epoxide (5, 6 beta-epoxy-5 beta-cholestan-3 beta-ol), and cholestanetriol (5 alpha-cholestane-3 beta, 5, 6 beta-triol) were isolated from plasma and liver of rabbits by high performance liquid chromatography and identified by gas-chromatography-mass spectrometry. The 5, 6-oxygenated cholestanols in the plasma and liver of rabbits fed for two months on a diet supplemented with cholesterol wee elevated to 2-5 times and 5-8 times for normal level, respectively. Among the 5, 6-oxy-generated steroids, the beta-epoxide existed at the highest level in tissues of both control and cholesterol-fed rabbits. The ratios of the beta-epoxide to the alpha-epoxide were 2-3 in all the examined biological specimens just as the previously demonstrated ones in the vitro lipid peroxidation-mediated reaction of cholesterol. These results strongly suggest that the epoxidation of the cholesterol double bond in the animal may be mediated by lipid peroxidation. The elevated 5, 6-oxygenated cholestanol levels on long term cholesterol feeding will be discussed in relation to a possible physiological role of cholestanetriol in regulation of tissue cholesterol levels. Topics: Animals; Cholestanols; Cholesterol; Cholesterol, Dietary; Liver; Oxidation-Reduction; Rabbits | 1980 |
Evidence of epoxide hydrase activity in human intestinal microflora.
Cholesterol-5 alpha, 6 alpha-epoxide has been implicated as an etiologic agent in human colon cancer. The epoxide is metabolized by human intestinal microflora to a product which was characterized by thin-layer and gas-liquid chromatography as well as combined gas-liquid chromatography-mass spectrometry. Chromatographic properties are identical with authentic cholestan-3 beta, 5 alpha, 6 beta-triol, and these results suggest that microbial epoxide hydrase activity is present in the human colon. Topics: Cholestanols; Cholesterol; Chromatography, Thin Layer; Colon; Enterobacteriaceae; Epoxide Hydrolases; Feces; Gas Chromatography-Mass Spectrometry; Humans | 1978 |