Disease relevance of cholest-5-ene-3beta,7beta-diol

• Different apoptotic mechanisms are involved in the antiproliferative effects of 7beta-hydroxysitosterol and 7beta-hydroxycholesterol in human colon cancer cells [1].
• Foam cell death induced by 7beta-hydroxycholesterol is mediated by labile iron-driven oxidative injury: mechanisms underlying induction of ferritin in human atheroma [2].
• Among all COP compounds tested, plasma 7beta-hydroxycholesterol was associated with lung cancer risk [3].
• 7beta-hydroxycholesterol reduces the extent of reactive gliosis caused by iron deposition in the hippocampus but does not attenuate the iron-induced seizures in rats [4].
• In a logistic regression model, which included also the Model for End-Stage Liver Disease (MELD) score, 7beta-hydroxycholesterol plasma concentration was an independent predictor of IPGF with an odds ratio of 1.17 (95% CI, 1.02-1.33, P = 0.028) [5].

High impact information on cholest-5-ene-3beta,7beta-diol

• Our study aimed at comparing antiproliferative effects of 7beta-hydroxysitosterol (7beta-OHsito) versus 7beta-hydroxycholesterol (7beta-OHchol) on the human colon cancer cell line Caco-2 [1].
• This ceramide generation is not attributed to caspase activation since inhibition of 7beta-hydroxycholesterol- and 7-ketocholesterol-induced apoptosis by Z-VAD-fmk (100 microM), a broad spectrum caspase inhibitor, did not reduce C16 : 0 and C24 : 1 ceramide species accumulation [6].
• Human IMA VSMCs from diabetic patients showed resistance to apoptosis, measured as DNA fragmentation and caspase-3 activation, induced by C-reactive protein (CRP) and other stimuli, such as hydrogen peroxide and 7beta-hydroxycholesterol [7].
• Induction of adaptive response and enhancement of PC12 cell tolerance by 7-hydroxycholesterol and 15-deoxy-delta(12,14)-prostaglandin J2 through up-regulation of cellular glutathione via different mechanisms [8].
• The rate of production of 7beta-hydroxycholesterol by APP was approximately 200 times lower than by beta-amyloid [9].

Chemical compound and disease context of cholest-5-ene-3beta,7beta-diol

• In the present study, we investigated the cytotoxic effects of 7beta-hydroxycholesterol (7betaOH), 7-ketocholesterol (7keto), 25-hydroxycholesterol (25OH), and 27-hydroxycholesterol (27OH) on U937 monocytic cells, both individually and in atheroma-relevant mixtures mimicking the oxysterol composition reported in human atheroma lesions [10].
• In this study, we investigated the effect of 7beta-hydroxycholesterol (7beta-OHCH) and 7ketocholesterol (7k-CH) on the growth and MAP kinase activity in three in vitro biological models: rat astrocyte primary cultures, primary cultures treated by dibutyryl-cAMP (reactive cells), and the C6 glioma cell line [11].
• In this study, we explored the inhibitory effects of the liposome containing 7beta-hydroxycholesterol on the reactive astrocytosis caused by the injection of iron into the hippocampus of rats and furthermore evaluated the involvement of reactive astrocytosis in iron-induced epilepsy [4].

Biological context of cholest-5-ene-3beta,7beta-diol

• Like MPO/H(2)O(2)/nitrite-oxLDL, 7beta-hydroxycholesterol was cytotoxic toward endothelial cells through eliciting oxidative stress [12].
• In all cells, both 7beta-hydroxycholesterol and 7-ketocholesterol exhibited toxic effects characterized by a loss of cell adhesion and an increased permeability to propidium iodide [13].
• They also suggest that enhancement of O2*- production associated with lipid peroxidation during 7beta-hydroxycholesterol and 7-ketocholesterol-induced apoptosis could contribute to in vivo vascular injury, and that myelin figures could constitute suitable markers of oxysterol-induced cell death [14].
• Detection of lipid peroxidation in vivo: total hydroxyoctadecadienoic acid and 7-hydroxycholesterol as oxidative stress marker [15].
• A new method for the extraction and quantification of cholesterol, 7-ketocholesterol, cholestane-3beta-5alpha-6beta-triol, 25-hydroxycholesterol, 5,6alpha-epoxycholesterol, and 7beta-hydroxycholesterol by means of reversed-phase LC/atmospheric pressure chemical ionization mass spectrometry is presented [16].

Anatomical context of cholest-5-ene-3beta,7beta-diol

• In the present investigation, we studied the relationship between ferritin induction and occurrence of apoptosis in 7beta-hydroxycholesterol (7beta-OH)-treated monocytic cells and macrophages [2].
• Thus, 7beta-hydroxycholesterol and 7-ketocholesterol have dual cytotoxic effects on the cells of the vascular wall by their ability to induce apoptosis in endothelial and smooth muscle cells and necrosis in fibroblasts [13].
• 7beta-Hydroxycholesterol has been previously demonstrated to inhibit astrocytosis in injured cortex or spinal cord of rats [4].
• By electron and fluorescence microscopy, myelin figures evocating autophagic vacuoles were barely observed under treatment with 7beta-hydroxycholesterol and 7-ketocholesterol, and their formation occurring before the loss of mitochondrial potential was reduced by Vit E [14].
• We have investigated the effect of kaempferol and rutin, active components of red wine, in the apoptosis induced by 7beta-hydroxycholesterol in rat vascular smooth muscle cells [17].

Associations of cholest-5-ene-3beta,7beta-diol with other chemical compounds

• Cytotoxicity of myeloperoxidase/nitrite-oxidized low-density lipoprotein toward endothelial cells is due to a high 7beta-hydroxycholesterol to 7-ketocholesterol ratio [12].
• Thin-layer chromatography of oxidized LDL lipids confirmed the loss of esterified cholesterol, and revealed multiple new bands, some of which matched reference oxysterols including 7-ketocholesterol, 5,6-epoxycholesterol, and 7-hydroxycholesterol [18].
• The side-chain hydroxylated oxysterols 25-hydroxycholesterol and 27-hydroxycholesterol were more potent in inducing apoptosis than 7beta-hydroxycholesterol and cholesterol-5alpha,6alpha-epoxide, as determined by TUNEL staining [19].
• The results of this study indicated that the oxysterol level, especially 7beta-hydroxycholesterol and 7-ketocholestrol, in the liver was lowered by the administration of ketoconazole and BHT, and HMG-CoA reductase activity was increased in response to these agents [20].
• Irradiation of MC540-sensitized membranes in the presence of added iron and ascorbate resulted in a large burst of lipid peroxidation, as shown by thiobarbituric acid reactivity and appearance of 7-hydroperoxycholesterol and 7-hydroxycholesterol as major oxidation products [21].

Gene context of cholest-5-ene-3beta,7beta-diol

• 7beta-Hydroxycholesterol inhibited secretion of soluble APP from cultured rat hippocampal H19-7/IGF-IR neuronal cells and inhibited tumor necrosis factor-alpha-converting enzyme alpha-secretase activity but had no effect on beta-site APP-cleaving enzyme 1 activity [9].
• The mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 (but not JNK) were activated within 5 min after addition of 7beta-hydroxycholesterol [19].
• Enrichment of MPM from control mice with the major oxysterols found in E(0) MPM (7-ketocholesterol, beta-epoxycholesterol and 7beta-hydroxycholesterol) resulted in a dose-dependent increase (60-80%) in PKC activity, AA release, p47phox translocation, superoxide anion release and cell-mediated oxidation of LDL [22].
• The 7-hydroxycholesterol in SRM 909, most of which appeared to be already present in the serum rather than formed during saponification, may account for as much as 20% of the observed difference between the methods [23].
• Lung cancer risk adjusted for sports activity significantly increased by 26% (CI = 1.050-1.506, P = 0.01) per unit (1 nmol/mmol plasma cholesterol) of 7beta-hydroxycholesterol [3].

Analytical, diagnostic and therapeutic context of cholest-5-ene-3beta,7beta-diol

• CBX significantly decreased the ratio of 7beta-hydroxycholesterol to 7KC, supporting the evidence from cell culture experiments for 11beta-HSD1-dependent reduction of 7KC to 7beta-hydroxycholesterol [24].
• High preoperative recipient plasma 7beta-hydroxycholesterol is associated with initial poor graft function after liver transplantation [5].
• Limitations of the single-cell gel electrophoresis assay to monitor apoptosis in U937 and HepG2 cells exposed to 7beta-hydroxycholesterol [25].
• 7Alpha-hydroxycholesterol or 7beta-hydroxycholesterol were incubated with rabbit, guinea pig, rat, hamster, and chicken microsomal suspensions and then extracted and analyzed using high-performance liquid chromatography (HPLC) [26].
• The use of lipid-coated microbubbles as a delivery agent of 7beta-hydroxycholesterol in a radiofrequency lesion in the rat brain [27].

References