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Sample records for cholesterol acyltransferase1 acat1

  1. Modulation Peroxisome Proliferators Activated Receptor alpha (PPAR α and Acyl Coenzyme A: Cholesterol Acyltransferase1 (ACAT1 Gene expression by Fatty Acids in Foam cell

    Directory of Open Access Journals (Sweden)

    Mojarrad Majed

    2009-09-01

    Full Text Available Abstract Background One of the most important factors in the initiation and progression of atherosclerosis is the default in macrophage cholesterol homeostasis. Many genes and transcription factors such as Peroxisome Proliferators Activated Receptors (PPARs and Acyl Coenzyme A: Cholesterol Acyltransferase1 (ACAT1 are involved in cholesterol homeostasis. Fatty Acids are important ligands of PPARα and the concentration of them can effect expression of ACAT1. So this study designed to clarified on the role of these genes and fatty acids on the lipid metabolism in foam cells. Methods This study examined effects of c9, t11-Conjugated Linoleic Acid(c9, t11-CLA, Alpha Linolenic Acid (LA, Eicosapentaenoic Acid (EPA on the PPARα and ACAT1 genes expression by using Real time PCR and cholesterol homeostasis in THP-1 macrophages derived foam cells. Results Incubation of c9, t11-CLA, LA cause a significant reduction in intracellular Total Cholesterol, Free Cholesterol, cellular and Estrified Cholesterol concentrations (P ≤ 0.05. CLA and LA had no significant effect on the mRNA levels of ACAT1, but EPA increased ACAT1 mRNA expression (P = 0.003. Treatment with EPA increased PPARα mRNA levels (P ≤ 0.001, although CLA, LA had no significant effect on PPARα mRNA expression. Conclusion In conclusion, it seems that different fatty acids have different effects on gene expression and lipid metabolism and for complete conception study of the genes involved in lipid metabolism in foam cell all at once maybe is benefit.

  2. Rosiglitazone inhibits expression of acyl-coenzyme A:cholesterol acyltransferase-1 in THP-1 macrophages induced by advanced glycation end-products

    Institute of Scientific and Technical Information of China (English)

    Yang Qihong; Xu Qiang; Zhang Hong; Si Liangyi

    2008-01-01

    Objective: To investigate the effects of rosiglitazone, a synthetic ligand of peroxisome proliferators-activated receptor gamma (PPARγ), on the expression of acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) in phorbol myristate acetate (PMA)-pretreated THP-1 cells after the inducement of advanced glycation end products (AGEs). Methods: After THP-1 cells were cultured in the presence of 0.1 umol/L PMA for 72 h to induce phagocytic differentiation, the obtained THP-1 macrophages were treated with rosiglitazone for 4 h at different concentrations (1,5 or 10 μmol/L) and then exposed to AGEs-modified bovine serum albumin (AGEs-BSA) for 24 h at a concentration of 200 mg/L. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis were performed to detect the mRNA and protein expressions of ACAT-1 respectively. Results: Administration of AGEs-BSA (200 mg/L) into the THP-1 macrophages resulted in up-regulation of ACAT-1 at mRNA and protein levels when compared with the expressions in macrophages incubated with serum-free RPM11640. Pretreatment of rosiglitazone inhibited significantly the increased expression of ACAT-1 induced by AGEs-BSA in a concentration-dependent manner. Conclusion: PPARγ activation by rosiglitazone down-regulates ACAT-1 expression induced by AGEs in THP-1 macrophages, which might provide a new way for treating atherogenesis in diabetic patients.

  3. Rimonabant is a dual inhibitor of acyl CoA:cholesterol acyltransferases 1 and 2.

    Science.gov (United States)

    Netherland, Courtney; Thewke, Douglas P

    2010-08-01

    Acyl coenzyme A:cholesterol acyltransferase (ACAT) catalyzes the intracellular synthesis of cholesteryl esters (CE). Both ACAT isoforms, ACAT1 and ACAT2, play key roles in the pathophysiology of atherosclerosis and ACAT inhibition retards atherosclerosis in animal models. Rimonabant, a type 1 cannabinoid receptor (CB1) antagonist, produces anti-atherosclerotic effects in humans and animals by mechanisms which are not completely understood. Rimonabant is structurally similar to two other cannabinoid receptor antagonists, AM251 and SR144528, recently identified as potent inhibitors of ACAT. Therefore, we examined the effects of Rimonabant on ACAT using both in vivo cell-based assays and in vitro cell-free assays. Rimonabant dose-dependently reduced ACAT activity in Raw 264.7 macrophages (IC(50)=2.9+/-0.38 microM) and isolated peritoneal macrophages. Rimonabant inhibited ACAT activity in intact CHO-ACAT1 and CHO-ACAT2 cells and in cell-free assays with approximately equal efficiency (IC(50)=1.5+/-1.2 microM and 2.2+/-1.1 microM for CHO-ACAT1 and CHO-ACAT2, respectively). Consistent with ACAT inhibition, Rimonabant treatment blocked ACAT-dependent processes in macrophages, oxysterol-induced apoptosis and acetylated-LDL induced foam cell formation. From these results we conclude that Rimonabant is an ACAT1/2 dual inhibitor and suggest that some of the atherosclerotic beneficial effects of Rimonabant are, at least partly, due to inhibition of ACAT. PMID:20609360

  4. Rimonabant is a dual inhibitor of acyl CoA:cholesterol acyltransferases 1 and 2

    OpenAIRE

    Netherland, Courtney; Thewke, Douglas P.

    2010-01-01

    Acyl-coenzymeA:cholesterol acyltransferase (ACAT) catalyzes the intracellular synthesis of cholesteryl esters (CE). Both ACAT isoforms, ACAT1 and ACAT2, play key roles in the pathophysiology of atherosclerosis and ACAT inhibition retards atherosclerosis in animal models. Rimonabant, a type 1 cannabinoid receptor (CB1) antagonist, produces anti-atherosclerotic effects in humans and animals by mechanisms which are not completely understood. Rimonabant is structurally similar to two other cannab...

  5. Cloning and functional analysis of human acyl coenzyme A: Cholesterol acyltransferase1 gene P1 promoter.

    Science.gov (United States)

    Ge, Jing; Cheng, Bei; Qi, Benling; Peng, Wen; Wen, Hui; Bai, Lijuan; Liu, Yun; Zhai, Wei

    2016-07-01

    Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1) catalyzes the conversion of free cholesterol (FC) to cholesterol ester. The human ACAT1 gene P1 promoter has been cloned. However, the activity and specificity of the ACAT1 gene P1 promoter in diverse cell types remains unclear. The P1 promoter fragment was digested with KpnI/XhoI from a P1 promoter cloning vector, and was subcloned into the multiple cloning site of the Firefly luciferase vector pGL3‑Enhancer to obtain the construct P1E‑1. According to the analysis of biological information, the P1E‑1 plasmid was used to generate deletions of the ACAT1 gene P1 promoter with varying 5' ends and an identical 3' end at +65 by polymerase chain reaction (PCR). All the 5'‑deletion constructs of the P1 promoter were identified by PCR, restriction enzyme digestion mapping and DNA sequencing. The transcriptional activity of each construct was detected after transient transfection into THP‑1, HepG2, HEK293 and Hela cells using DEAE‑dextran and Lipofectamine 2000 liposome transfection reagent. Results showed that the transcriptional activity of the ACAT1 gene P1 promoter and deletions of P1 promoter in THP‑1 and HepG2 cells was higher than that in HEK293 and HeLa cells. Moreover, the transcriptional activity of P1E‑9 was higher compared with those of other deletions in THP‑1, HepG2, HEK293 and HeLa cells. These findings indicate that the transcriptional activity of the P1 promoter and the effects of deletions vary with different cell lines. Thus, the P1 promoter may drive ACAT1 gene expression with cell‑type specificity. In addition, the core sequence of ACAT1 gene P1 promoter was suggested to be between -125 and +65 bp. PMID:27220725

  6. Enhancement of human ACAT1 gene expression to promote the macrophage-derived foam cell formation by dexamethasone

    Institute of Scientific and Technical Information of China (English)

    Li YANG; Ta Yuan CHANG; Bo Liang LI; Jin Bo YANG; Jia CHEN; Guang Yao YU; Pei ZHOU; Lei LEI; Zhen Zhen WANG; Catherine CY CHANG; XinYing YANG

    2004-01-01

    In macrophages, the accumulation of cholesteryl esters synthesized by the activated acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) results in the foam cell formation, a hallmark of early atherosclerotic lesions. In this study,with the treatment of a glucocorticoid hormone dexamethasone (Dex), lipid staining results clearly showed the large accumulation of lipid droplets containing cholesteryl esters in THP- 1-derived macrophages exposed to lower concentration of the oxidized low-density lipoprotein (ox-LDL). More notably, when treated together with specific anti-ACAT inhibitors, the abundant cholesteryl ester accumulation was markedly diminished in THP-l-derived macrophages, confirming that ACAT is the key enzyme responsible for intracellular cholesteryl ester synthesis. RT-PCR and Western blot results indicated that Dex caused up-regulation of human ACAT1 expression at both the mRNA and protein levels in THP-1 and THP- 1-derived macrophages. The luciferase activity assay demonstrated that Dex could enhance the activity of human ACAT1 gene P1 promoter, a major factor leading to the ACAT1 activation, in a cell-specific manner.Further experimental evidences showed that a glucocorticoid response element (GRE) located within human ACAT1gene P1 promoter to response to the elevation of human ACAT1 gene expression by Dex could be functionally bound with glucocorticoid receptor (GR) proteins. These data supported the hypothesis that the clinical treatment with Dex,which increased the incidence of atherosclerosis, may in part due to enhancing the ACAT1 expression to promote the accumulation of cholesteryl esters during the macrophage-derived foam cell formation, an early stage of atherosclerosis.

  7. Production of ACAT1 56-kDa isoform in human cells via trans-splicing involving the ampicillin resistance gene

    Institute of Scientific and Technical Information of China (English)

    Guang-Jing Hu; Jia Chen; Xiao-Nan Zhao; Jia-Jia Xu; Dong-Qing Guo; Ming Lu; Ming Zhu

    2013-01-01

    Trans-splicing,a process involving the cleavage and joining of two separate transcripts,can expand the transcriptome and proteome in eukaryotes.Chimeric RNAs generated by trans-splicing are increasingly described in literatures.The widespread presence of antibiotic resistance genes in natural environments and human intestines is becoming an important challenge for public health.Certain antibiotic resistance genes,such as ampicillin resistance gene (Amp),are frequently used in recombinant plasmids.Until now,trans-splicing involving recombinant plasmid-derived exogenous transcripts and endogenous cellular RNAs has not been reported.Acyl-CoA:cholesterol acyltransferase 1 (ACAT1) is a key enzyme involved in cellular cholesterol homeostasis.The 4.3-kb human ACAT1 chimeric mRNA can produce 50-kDa and 56-kDa isoforms with different enzymatic activities.Here,we show that human ACAT1 56-kDa isoform is produced from an mRNA species generated through the trans-splicing of an exogenous transcript encoded by the antisense strand of Ampr (asAmp) present in common Ampr-plasmids and the 4.3-kb endogenous ACAT1 chimeric mRNA,which is presumably processed through a prior event of interchromosomal trans-splicing.Strikingly,DNA fragments containing the asAmp with an upstream recombined cryptic promoter and the corresponding exogenous asAmp transcripts have been detected in human cells.Our findings shed lights on the mechanism of human ACAT1 56-kDa isoform production,reveal an exogenous-endogenous trans-splicing system,in which recombinant plasmid-derived exogenous transcripts are linked with endogenous cellular RNAs in human cells,and suggest that exogenous DNA might affect human gene expression at both DNA and RNA levels.

  8. 正常中国人及内源性高甘油三酯血症患者酰基辅酶A:胆固醇酰基转移酶基因多态性的研究%Analysis of acyl-coenzyme A:cholesterol acyltransferase 1 polymorphism in patients with endogenous hypertriglyceridemia in Chinese population

    Institute of Scientific and Technical Information of China (English)

    李琴; 白怀; 范平; 刘瑞; 刘宇; 刘秉文

    2008-01-01

    目的 研究酰基辅酶A:胆固醇酰基转移酶1(acyl-coenzyme A:cholesterol acyltransferase 1,ACAT1)基因rs1044925多态性是否与正常汉族中国人及内源性高甘油三酯血症(hypertriglyceridemia,HTG)患者血脂及载脂蛋白水平存在关联.方法 应用聚合酶链反应-限制性片段长度多态性分析法,对成都地区372名汉族人(267名正常人和105例内源性高甘油三酯血症患者)ACAT1基因rs1044925多态位点进行分析.结果 中国人ACAT1基因rs1044925多态位点C等位基因频率为0.137,显著低于中部和南部欧洲人的0.354(P<0.05);HTG组和对照组C等位基因频率分别为0.153和0.137,两者之间差异无统计学意义.对照组AA基因型携带者血清低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)和非高密度脂蛋白胆固醇(non-high density lipoprotein cholesterol,nHDL-C)水平均较C等位基因携带者(Ac和CC基因型者)显著升高[(3.25±0.68)mmol/L vs(3.03±0.87)mmol/L,P<0.05;(3.80±0.71)mmol/L vs(3.23±0.82)mmol/L,P<0.05],HTG组AA基因型携带者血清高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-c)水平较C等位基因携带者显著升高[(1.00±0.28)mmol/L vs(0.87±0.17)mmoL/L,P<0.05].结论 ACAT1 基因rs1044925多态性不仅与正常中国成都地区汉族人血清LDL-C、nHDL-C含量有关,而且还与内源性高甘油三酯血症患者血清HDL-C水平相关联.%Objective To investigate the polymorphism of acyl-coenzyme A:cholesterol acyltransfemse 1(ACAT1)gene and its relationship with endogenous hypertriglyceridemia(HTG)in Chinese population.Methods A total of three hundred and seventy-two subjects(105 endogenous hypertriglyceridemics and 267 healthy controls)from a population of Chinese Han nationality in Chengdu area were studied using PCR-restriction fragment length polymorphism (RFLP).Results The frequency of C allele in normal Chinese at rs1044925 locus was 0.137,which was lower thanthat reported in the

  9. ACAT1 deletion in murine macrophages associated with cytotoxicity and decreased expression of collagen type 3A1

    International Nuclear Information System (INIS)

    In contrast to some published studies of murine macrophages, we previously showed that ACAT inhibitors appeared to be anti-atherogenic in primary human macrophages in that they decreased foam cell formation without inducing cytotoxicity. Herein, we examined foam cell formation and cytotoxicity in murine ACAT1 knockout (KO) macrophages in an attempt to resolve the discrepancies. Elicited peritoneal macrophages from normal C57BL6 and ACAT1 KO mice were incubated with DMEM containing acetylated LDL (acLDL, 100 μg protein/ml) for 48 h. Cells became cholesterol enriched and there were no differences in the total cholesterol mass. Esterified cholesterol mass was lower in ACAT1 KO foam cells compared to normal macrophages (p 14C]adenine from macrophages, was approximately 2-fold greater in ACAT1 KO macrophages as compared to normal macrophages (p < 0.0001), and this was independent of cholesterol enrichment. cDNA microarray analysis showed that ACAT1 KO macrophages expressed substantially less collagen type 3A1 (26-fold), which was confirmed by RT-PCR. Total collagen content was also significantly reduced (57%) in lung homogenates isolated from ACAT1 KO mice (p < 0.02). Thus, ACAT1 KO macrophages show biochemical changes consistent with increased cytotoxicity and also a novel association with decreased expression of collagen type 3A1

  10. The optional long 5'-untranslated region of human ACAT1 mRNAs impairs the production of ACAT1 protein by promoting its mRNA decay

    Institute of Scientific and Technical Information of China (English)

    Xiaonan Zhao; Baoliang Song; Tayuan Chang; Boliang Li; Jia Chen; Lei Lei; Guangjing Hu; Ying Xiong; Jiajia Xu; Qin Li; Xinying Yang; Catherine C.Y.Chang

    2009-01-01

    We have previously reported that human ACAT1 mRNAs produce the 50 kDa protein using the AUG1397-1399 initiation codon,and also a minor 56 kDa isoform using the upstream in-frame GGC1274-1276initiation codon.The GGC1274-1276 codon is located at the optional long 5'-untranslated region(5'-UTR,nt 1-1396)of the mRNAs.The DNA sequences corresponding to this 5'-UTR are located in two different chromosomes,7 and 1.In the current work,we report that the optional long 5'-UTR significantly impairs the production of human ACAT1 protein initiated from the AUG1397-1399 codon,mainly by promoting its mRNA decay.The western blot analyses indicated that the optional long 5'-UTR potently impaired the production of different proteins initiated from the AUG1397-1399codon,meaning that this impairing effect was not influenced by the 3'-UTR or the coding sequence of ACAT1 mRNA.The results of reverse transcription-quantitative polymerase chain reaction demonstrated that this 5'-UTR dramatically reduced the contents of its linked mRNAs.Analyses of the protein to mRNA ratios showed that this 5'-UTR mainly decreased its mRNA stability rather than altering its translational efficiency.We next performed the plasmid transfection experiments and used actinomycin D to inhibit transcription.The results showed that this 5'-UTR promoted its mRNA decay.Additional transfection and nucleofection experiments using RNAs prepared in vitro illustrated that,in both the cytoplasm and the nucleus of cells,the optional long 5'-UTR-linked mRNAs decayed faster than those without the link.Overall,our study brings new insight to the regulation of the human ACAT1 gene expression at the post-transcription level.

  11. Biosynthesis of phosphatidylcholine by human lysophosphatidylcholine acyltransferase 1.

    Science.gov (United States)

    Harayama, Takeshi; Shindou, Hideo; Shimizu, Takao

    2009-09-01

    Pulmonary surfactant is a complex of phospholipids and proteins lining the alveolar walls of the lung. It reduces surface tension in the alveoli, and is critical for normal respiration. Pulmonary surfactant phospholipids consist mainly of phosphatidylcholine (PC) and phosphatidylglycerol (PG). Although the phospholipid composition of pulmonary surfactant is well known, the enzyme(s) involved in its biosynthesis have remained obscure. We previously reported the cloning of murine lysophosphatidylcholine acyltransferase 1 (mLPCAT1) as a potential biosynthetic enzyme of pulmonary surfactant phospholipids. mLPCAT1 exhibits lysophosphatidylcholine acyltransferase (LPCAT) and lysophosphatidylglycerol acyltransferase (LPGAT) activities, generating PC and PG, respectively. However, the enzymatic activity of human LPCAT1 (hLPCAT1) remains controversial. We report here that hLPCAT1 possesses LPCAT and LPGAT activities. The activity of hLPCAT1 was inhibited by N-ethylmaleimide, indicating the importance of some cysteine residue(s) for the catalysis. We found a conserved cysteine (Cys(211)) in hLPCAT1 that is crucial for its activity. Evolutionary analyses of the close homologs of LPCAT1 suggest that it appeared before the evolution of teleosts and indicate that LPCAT1 may have evolved along with the lung to facilitate respiration. hLPCAT1 mRNA is highly expressed in the human lung. We propose that hLPCAT1 is the biosynthetic enzyme of pulmonary surfactant phospholipids. PMID:19383981

  12. RNA secondary structures located in the interchromosomal region of human ACAT1 chimeric mRNA are re-quired to produce the 56-kDa isoform

    Institute of Scientific and Technical Information of China (English)

    Jia Chen; Ta-Yuan Chang; Bo-Liang Li; Xiao-Nan Zhao; Li Yang; Guang-Jing Hu; Ming Lu; Ying Xiong; Xin-Ying Yang; Catherine CY Chang; Bao-Liang Song

    2008-01-01

    We have previously reported that the human ACAT1 gene produces a chimeric mRNAthrough the interchromosomal processing of two discontinuous RNAs transcribed from chromosomes 1 and 7. The chimeric mRNA uses AUG1397-1399 and GGC1274-1276 as translation initiation codons to produce normal 50-kDa ACATI and a novel enzymatically active 56-kDa isoform,respectively,with the latter being authentically present in human cells,including human monocyte derived macrophages. In this work,we report that RNA secondary structures located in the vicinity,of the GGC1274-1276 codon are required for production of the 56-kDa isoform. The effects of the three predicted stem-loops (nt 1255-1268,1286-1342 and 1355-1384) were tested individually by transfecting expression plasmids into cells that contained the wild-type,deleted or mutant stem-loop sequences linked to a partial ACAT1 AUG open reading frame (ORF) or to theORFs of other genes. The expression patterns were monitored by western blot analyses. We found that the upstream stem-loop1255-1268 from chromosome 7 and downstream stem-loop1286-1342 from chromosome I were needed for production of the 56-kDa isoform,whereas the last stem-ioop1355-1384 from chromosome I was dispensable. The results of experi ments using both monocistronic and bicistronic vectors with a stable hairpin showed that translation initiation from the GGC1274-1276 codon was mediated by an internal ribosome entry site (IRES). Further experiments revealed that translation initiation from the GGC1274-1276 codon requires the upstream AU-constituted RNA secondary structure and the downstream GC-rich structure. This mechanistic work provides further support for the biological significance of the chimeric nature of the human ACATI transcript.

  13. Diacylglycerol acyltransferase-1 (DGAT1 inhibition perturbs postprandial gut hormone release.

    Directory of Open Access Journals (Sweden)

    Hua V Lin

    Full Text Available Diacylglycerol acyltransferase-1 (DGAT1 is a potential therapeutic target for treatment of obesity and related metabolic diseases. However, the degree of DGAT1 inhibition required for metabolic benefits is unclear. Here we show that partial DGAT1 deficiency in mice suppressed postprandial triglyceridemia, led to elevations in glucagon-like peptide-1 (GLP-1 and peptide YY (PYY only following meals with very high lipid content, and did not protect from diet-induced obesity. Maximal DGAT1 inhibition led to enhanced GLP-1 and PYY secretion following meals with physiologically relevant lipid content. Finally, combination of DGAT1 inhibition with dipeptidyl-peptidase-4 (DPP-4 inhibition led to further enhancements in active GLP-1 in mice and dogs. The current study suggests that targeting DGAT1 to enhance postprandial gut hormone secretion requires maximal inhibition, and suggests combination with DPP-4i as a potential strategy to develop DGAT1 inhibitors for treatment of metabolic diseases.

  14. Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol acyltransferase 1 (DGAT1) leading to a clinical candidate dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687).

    Science.gov (United States)

    Barlind, Jonas G; Bauer, Udo A; Birch, Alan M; Birtles, Susan; Buckett, Linda K; Butlin, Roger J; Davies, Robert D M; Eriksson, Jan W; Hammond, Clare D; Hovland, Ragnar; Johannesson, Petra; Johansson, Magnus J; Kemmitt, Paul D; Lindmark, Bo T; Morentin Gutierrez, Pablo; Noeske, Tobias A; Nordin, Andreas; O'Donnell, Charles J; Petersson, Annika U; Redzic, Alma; Turnbull, Andrew V; Vinblad, Johanna

    2012-12-13

    A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers. PMID:23116186

  15. Effects of the diacylglycerol o-acyltransferase 1 (DGAT1) K232A polymorphism on fatty acid, protein, and mineral composition of dairy cattle milk

    NARCIS (Netherlands)

    Bovenhuis, H.; Visker, M.H.P.W.; Poulsen, N.A.; Sehested, J.; Valenberg, van H.J.F.; Arendonk, van J.A.M.; Larsen, L.B.; Buitenhuis, A.J.

    2015-01-01

    Several studies have described associations between the diacylglycerol o-acyltransferase 1 (DGAT1) K232A polymorphism and routinely collected milk production traits but not much is known about effects of the DGAT1 polymorphism on detailed milk composition. The aim of this study was to estimate ef

  16. What's Cholesterol?

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    ... Skiing, Snowboarding, Skating Crushes What's a Booger? What's Cholesterol? KidsHealth > For Kids > What's Cholesterol? Print A A ... thing for food to be low in it? Cholesterol and Your Body Cholesterol (say: kuh-LES-tuh- ...

  17. About Cholesterol

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    ... High Blood Pressure Tools & Resources Stroke More About Cholesterol Updated:Aug 10,2016 It may surprise you ... our bodies to keep us healthy. What is cholesterol and where does it come from? Cholesterol is ...

  18. Cholesterol (image)

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    Cholesterol is a soft, waxy substance that is present in all parts of the body including the ... and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed ...

  19. Good vs. Bad Cholesterol

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    ... Pressure Tools & Resources Stroke More Good vs. Bad Cholesterol Updated:Mar 23,2016 Cholesterol can't dissolve ... test . View an animation of cholesterol . LDL (Bad) Cholesterol LDL cholesterol is considered the “bad” cholesterol because ...

  20. Membrane plasmalogen composition and cellular cholesterol regulation: a structure activity study

    Directory of Open Access Journals (Sweden)

    Su-Myat Khine K

    2010-06-01

    Full Text Available Abstract Background Disrupted cholesterol regulation leading to increased circulating and membrane cholesterol levels is implicated in many age-related chronic diseases such as cardiovascular disease (CVD, Alzheimer's disease (AD, and cancer. In vitro and ex vivo cellular plasmalogen deficiency models have been shown to exhibit impaired intra- and extra-cellular processing of cholesterol. Furthermore, depleted brain plasmalogens have been implicated in AD and serum plasmalogen deficiencies have been linked to AD, CVD, and cancer. Results Using plasmalogen deficient (NRel-4 and plasmalogen sufficient (HEK293 cells we investigated the effect of species-dependent plasmalogen restoration/augmentation on membrane cholesterol processing. The results of these studies indicate that the esterification of cholesterol is dependent upon the amount of polyunsaturated fatty acid (PUFA-containing ethanolamine plasmalogen (PlsEtn present in the membrane. We further elucidate that the concentration-dependent increase in esterified cholesterol observed with PUFA-PlsEtn was due to a concentration-dependent increase in sterol-O-acyltransferase-1 (SOAT1 levels, an observation not reproduced by 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA reductase inhibition. Conclusion The present study describes a novel mechanism of cholesterol regulation that is consistent with clinical and epidemiological studies of cholesterol, aging and disease. Specifically, the present study describes how selective membrane PUFA-PlsEtn enhancement can be achieved using 1-alkyl-2-PUFA glycerols and through this action reduce levels of total and free cholesterol in cells.

  1. Interactions of Several Lipid-Related Gene Polymorphisms and Cigarette Smoking on Blood Pressure Levels

    Directory of Open Access Journals (Sweden)

    Rui-Xing Yin, Dong-Feng Wu, Jin-Zhen Wu, Xiao-Li Cao, Lynn Htet Htet Aung, Lin Miao, Xing-Jiang Long, Wan-Ying Liu, Lin Zhang, Meng Li

    2012-01-01

    Full Text Available The interactions of single nucleotide polymorphisms (SNPs and cigarette smoking on blood pressure levels are limited. The present study was undertaken to detect nine lipid-related SNPs and their interactions with cigarette smoking on blood pressure levels. Genotyping of ATP-binding cassette transporter A1 (ABCA-1 V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1 rs1044925, low density lipoprotein receptor (LDL-R AvaⅡ, hepatic lipase gene (LIPC -250G>A, endothelial lipase gene (LIPG 584C>T, methylenetetrahydrofolate reductase (MTHFR 677C>T, proprotein convertase subtilisin-like kexin type 9 (PCSK9 E670G, peroxisome proliferator-activated receptor delta (PPARD +294T>C, and Scavenger receptor class B type 1 (SCARB1 rs5888 was performed in 935 nonsmokers and 845 smokers. The interactions were detected by factorial regression analysis. The frequencies of genotypes (ACAT-1 and LIPG, alleles (ABCA-1, and both genotypes and alleles (LDL-R, LIPC, PPARD and SCARB1 were different between nonsmokers and smokers (P < 0.05-0.001. The levels of pulse pressure (PP, ABCA-1, and systolic, diastolic blood pressure (SBP, DBP and PP (LIPC in nonsmokers were different among the genotypes (P < 0.01-0.001. The levels of SBP (ABCA-1, ACAT-1, LIPG and PCSK9, DBP (ACAT-1, LDL-R, LIPC, PCSK9 and PPARD, and PP (LIPC, LIPG, MTHFR and PCSK9 in smokers were different among the genotypes (P < 0.01-0.001. The SNPs of ABCA-1, ACAT-1 and PCSK9; ACAT-1, LDL-R, MTHFR and PCSK9; and ABCA-1, LIPC, PCSK9 and PPARD were shown interactions with cigarette smoking to influence SBP, DBP and PP levels (P < 0.05-0.001; respectively. The differences in blood pressure levels between the nonsmokers and smokers might partly result from different interactions of several SNPs and cigarette smoking.

  2. Cholesterol Test

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    ... seen when there is an existing problem like malnutrition , liver disease , or cancer . However there is no ... cholesterol levels include anabolic steroids, beta blockers , epinephrine, oral contraceptives, and vitamin D. ^ Back to top ... Health Professionals Get the Mobile App iTunes | Android | Kindle ...

  3. Cholesterol and Your Child

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    ... Tropical Delight: Melon Smoothie Pregnant? Your Baby's Growth Cholesterol and Your Child KidsHealth > For Parents > Cholesterol and ... child's risk of developing heart disease later. About Cholesterol Cholesterol is a waxy substance produced by the ...

  4. Women and Cholesterol

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    ... Blood Pressure Tools & Resources Stroke More Women and Cholesterol Updated:Apr 1,2016 The female sex hormone ... Glossary Related Sites Nutrition Center My Life Check Cholesterol • Home • About Cholesterol • Why Cholesterol Matters • Understand Your ...

  5. HDL Cholesterol Test

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    ... limited. Home Visit Global Sites Search Help? HDL Cholesterol Share this page: Was this page helpful? Also ... HDL; HDL-C Formal name: High-density Lipoprotein Cholesterol Related tests: Cholesterol ; LDL Cholesterol ; Triglycerides ; Lipid Profile ; ...

  6. LDL Cholesterol Test

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    ... limited. Home Visit Global Sites Search Help? LDL Cholesterol Share this page: Was this page helpful? Also ... LDL; LDL-C Formal name: Low-Density Lipoprotein Cholesterol Related tests: Cholesterol ; HDL Cholesterol ; Triglycerides ; Lipid Profile ; ...

  7. Cholesterol IQ Quiz

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    ... Pressure High Blood Pressure Tools & Resources Stroke More Cholesterol IQ Quiz Updated:Feb 2,2015 Begin the quiz Cholesterol • Home • About Cholesterol Introduction Good vs. Bad Cholesterol ...

  8. Effects of the diacylglycerol o-acyltransferase 1 (DGAT1) K232A polymorphism on fatty acid, protein, and mineral composition of dairy cattle milk.

    Science.gov (United States)

    Bovenhuis, H; Visker, M H P W; Poulsen, N A; Sehested, J; van Valenberg, H J F; van Arendonk, J A M; Larsen, L B; Buitenhuis, A J

    2016-04-01

    Several studies have described associations between the diacylglycerol o-acyltransferase 1 (DGAT1) K232A polymorphism and routinely collected milk production traits but not much is known about effects of the DGAT1 polymorphism on detailed milk composition. The aim of this study was to estimate effects of the DGAT1 polymorphism on milk fatty acid, protein, and mineral composition. We looked for effects that were significant and consistent in Danish Holstein Friesian (HF), Danish Jersey, and Dutch HF as these are likely to be true effects of the DGAT1 K232A polymorphism rather than being effects of linked loci. For fatty acid composition, significant and consistent effects of the DGAT1 polymorphism were detected on C14:0, C16:0, C15:0, C16:1, C18:1 cis-9, conjugated linoleic acid (CLA) cis-9,trans-11, C18:2 cis-9,cis-12, and C18:3 cis-9,cis-12,cis-15 content (percent by weight, wt/wt %). For C16:0, C16:1, and C18:1 cis-9, the DGAT1 polymorphism explained more than 10% of the phenotypic variation. Significant effects on milk protein composition in Dutch HF could not be confirmed in Danish Jersey or Danish HF. For mineral content, significant and consistent effects of the DGAT1 polymorphism on calcium, phosphorus, and zinc were detected. In the Dutch HF population, the contribution of the DGAT1 K232A polymorphism to phenotypic variance was 12.0% for calcium, 8.3% for phosphorus, and 6.1% for zinc. Different from effects on fatty acid composition, effects of the DGAT1 polymorphism on yields of long-chain fatty acids C18:1 cis-9, CLA cis-9,trans-11, C18:2 cis-9,cis-12, and C18:3 cis-9,cis-12,cis-15 were not significant. This indicates that effects of DGAT1 on these fatty acids are indirect, not direct, effects: DGAT1 affects de novo synthesis of fatty acids and, consequently, the contribution of the long-chain fatty acids to total fat is decreased. In addition, effects of the DGAT1 polymorphism on yields of Ca, P, and Zn were not significant, which indicates that effects

  9. Novel role of a triglyceride-synthesizing enzyme: DGAT1 at the crossroad between triglyceride and cholesterol metabolism

    Science.gov (United States)

    Sachdev, Vinay; Leopold, Christina; Bauer, Raimund; Patankar, Jay V.; Iqbal, Jahangir; Obrowsky, Sascha; Boverhof, Renze; Doktorova, Marcela; Scheicher, Bernhard; Goeritzer, Madeleine; Kolb, Dagmar; Turnbull, Andrew V.; Zimmer, Andreas; Hoefler, Gerald; Hussain, M. Mahmood; Groen, Albert K.; Kratky, Dagmar

    2016-01-01

    Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in triacylglycerol (TG) biosynthesis. Here we show that genetic deficiency and pharmacological inhibition of DGAT1 in mice alters cholesterol metabolism. Cholesterol absorption, as assessed by acute cholesterol uptake, was significantly decreased in the small intestine and liver upon DGAT1 deficiency/inhibition. Ablation of DGAT1 in the intestine (I-DGAT1−/−) alone is sufficient to cause these effects. Consequences of I-DGAT1 deficiency phenocopy findings in whole-body DGAT1−/− and DGAT1 inhibitor-treated mice. We show that deficiency/inhibition of DGAT1 affects cholesterol metabolism via reduced chylomicron size and increased trans-intestinal cholesterol excretion. These effects are independent of cholesterol uptake at the apical surface of enterocytes but mediated through altered dietary fatty acid metabolism. Our findings provide insight into a novel role of DGAT1 and identify a pathway by which intestinal DGAT1 deficiency affects whole-body cholesterol homeostasis in mice. Targeting intestinal DGAT1 may represent a novel approach for treating hypercholesterolemia. PMID:27344248

  10. Novel role of a triglyceride-synthesizing enzyme: DGAT1 at the crossroad between triglyceride and cholesterol metabolism.

    Science.gov (United States)

    Sachdev, Vinay; Leopold, Christina; Bauer, Raimund; Patankar, Jay V; Iqbal, Jahangir; Obrowsky, Sascha; Boverhof, Renze; Doktorova, Marcela; Scheicher, Bernhard; Goeritzer, Madeleine; Kolb, Dagmar; Turnbull, Andrew V; Zimmer, Andreas; Hoefler, Gerald; Hussain, M Mahmood; Groen, Albert K; Kratky, Dagmar

    2016-09-01

    Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in triacylglycerol (TG) biosynthesis. Here we show that genetic deficiency and pharmacological inhibition of DGAT1 in mice alters cholesterol metabolism. Cholesterol absorption, as assessed by acute cholesterol uptake, was significantly decreased in the small intestine and liver upon DGAT1 deficiency/inhibition. Ablation of DGAT1 in the intestine (I-DGAT1(-/-)) alone is sufficient to cause these effects. Consequences of I-DGAT1 deficiency phenocopy findings in whole-body DGAT1(-/-) and DGAT1 inhibitor-treated mice. We show that deficiency/inhibition of DGAT1 affects cholesterol metabolism via reduced chylomicron size and increased trans-intestinal cholesterol excretion. These effects are independent of cholesterol uptake at the apical surface of enterocytes but mediated through altered dietary fatty acid metabolism. Our findings provide insight into a novel role of DGAT1 and identify a pathway by which intestinal DGAT1 deficiency affects whole-body cholesterol homeostasis in mice. Targeting intestinal DGAT1 may represent a novel approach for treating hypercholesterolemia. PMID:27344248

  11. What Is Cholesterol?

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Cholesterol KidsHealth > For Teens > Cholesterol Print A A A ... High Cholesterol? en español ¿Qué es el colesterol? Cholesterol Is a Fat in the Blood Cholesterol (kuh- ...

  12. Cholesterol and lifestyle

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000099.htm Cholesterol and lifestyle To use the sharing features on ... Stroke Serious heart or blood vessel disease Your Cholesterol Numbers All men should have their blood cholesterol ...

  13. Cholesterol testing and results

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000386.htm Cholesterol testing and results To use the sharing features ... can tell you what your goal should be. Cholesterol Tests Some cholesterol is considered good and some ...

  14. Cholesterol Facts and Statistics

    Science.gov (United States)

    ... Blood Pressure Salt Million Hearts® WISEWOMAN Program High Cholesterol Facts Recommend on Facebook Tweet Share Compartir As ... the facts about high cholesterol [PDF-281K] . High Cholesterol in the United States 73.5 million adults ( ...

  15. Apolipoprotein A-I Helsinki promotes intracellular acyl-CoA cholesterol acyltransferase (ACAT) protein accumulation.

    Science.gov (United States)

    Toledo, Juan D; Garda, Horacio A; Cabaleiro, Laura V; Cuellar, Angela; Pellon-Maison, Magali; Gonzalez-Baro, Maria R; Gonzalez, Marina C

    2013-05-01

    Reverse cholesterol transport is a process of high antiatherogenic relevance in which apolipoprotein AI (apoA-I) plays an important role. The interaction of apoA-I with peripheral cells produces through mechanisms that are still poorly understood the mobilization of intracellular cholesterol depots toward plasma membrane. In macrophages, these mechanisms seem to be related to the modulation of the activity of acyl-CoA cholesterol acyltransferase (ACAT), the enzyme responsible for the intracellular cholesterol ester biosynthesis that is stored in lipid droplets. The activation of ACAT and the accumulation of lipid droplets play a key role in the transformation of macrophages into foam cells, leading to the formation of atheroma or atherosclerotic plaque. ApoA-I Helsinki (or ∆K107) is a natural apoA-I variant with a lysine deletion in the central protein region, carriers of which have increased atherosclerosis risk. We herein show that treatment of cultured RAW macrophages or CHOK1 cells with ∆K107, but not with wild-type apoA-I or a variant containing a similar deletion at the C-terminal region (∆K226), lead to a marked increase (more than 10 times) in the intracellular ACAT1 protein level as detected by western blot analysis. However, we could only detect a slight increase in cholesteryl ester produced by ∆K107 mainly when Chol loading was supplied by low-density lipoprotein (LDL). Although a similar choline-phospholipid efflux is evoked by these apoA-I variants, the change in phosphatidylcholine/sphyngomyelin distribution produced by wild-type apoA-I is not observed with either ∆K107 or ∆K226. PMID:23456478

  16. Reverse cholesterol transport revisited

    Institute of Scientific and Technical Information of China (English)

    Astrid; E; van; der; Velde

    2010-01-01

    Reverse cholesterol transport was originally described as the high-density lipoprotein-mediated cholesterol flux from the periphery via the hepatobiliary tract to the intestinal lumen, leading to fecal excretion. Since the introduction of reverse cholesterol transport in the 1970s, this pathway has been intensively investigated. In this topic highlight, the classical reverse cholesterol transport concepts are discussed and the subject reverse cholesterol transport is revisited.

  17. Cholesterol - drug treatment

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

  18. Get Your Cholesterol Checked

    Science.gov (United States)

    ... You also get cholesterol by eating foods like egg yolks, fatty meats, and regular cheese. If you have too much cholesterol in your body, it can build up inside your blood vessels and make it hard for blood to ...

  19. Common Misconceptions about Cholesterol

    Science.gov (United States)

    ... your doctor recommends. Learn more about eating a healthy diet. Thin people don't have to worry about high cholesterol. A person with any body type can have high cholesterol. Overweight people are more likely to have ... heart-healthy. Have your cholesterol checked regularly regardless of your ...

  20. Home-Use Tests - Cholesterol

    Science.gov (United States)

    ... Medical Procedures In Vitro Diagnostics Home Use Tests Cholesterol Share Tweet Linkedin Pin it More sharing options ... a home-use test kit to measure total cholesterol. What cholesterol is: Cholesterol is a fat (lipid) ...

  1. National Cholesterol Education Month

    Centers for Disease Control (CDC) Podcasts

    2009-09-01

    Do you know your cholesterol numbers? Your doctor can do a simple test to check your cholesterol levels and help you make choices that lower your risk for heart disease and stroke.  Created: 9/1/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/9/2009.

  2. Bile acid sequestrants for cholesterol

    Science.gov (United States)

    ... ency/patientinstructions/000787.htm Bile acid sequestrants for cholesterol To use the sharing features on this page, ... are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can stick ...

  3. What Causes High Blood Cholesterol?

    Science.gov (United States)

    ... the NHLBI on Twitter. What Causes High Blood Cholesterol? Many factors can affect the cholesterol levels in your blood. You can control some ... but not others. Factors You Can Control Diet Cholesterol is found in foods that come from animal ...

  4. Lifestyle Changes and Cholesterol

    Science.gov (United States)

    ... Pressure High Blood Pressure Tools & Resources Stroke More Lifestyle Changes and Cholesterol Updated:Oct 26,2015 As ... disease and stroke, your doctor may suggest some lifestyle changes. Regardless of whether your plan includes drug ...

  5. HDL cholesterol: atherosclerosis and beyond

    OpenAIRE

    Stroes, E. S. G.; Hovingh, G. K.; Kuivenhoven, J. A.; Bochem, A.E.

    2013-01-01

    Cardiovascular disease (CVD) is the leading cause of death in the Western world. Myocardial infarction and stroke are the result of a compromised blood flow which may result from cholesterol accumulation in the vessel wall due to high plasma levels of LDL cholesterol. High plasma levels of HDL cholesterol, however, are inversely associated with CVD. This is commonly ascribed to a concept called "reverse cholesterol transport" a mechanism by which the HDL particle takes up cholesterol from the...

  6. Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation.

    Science.gov (United States)

    Lee, H J; Ryu, J M; Jung, Y H; Lee, K H; Kim, D I; Han, H J

    2016-01-01

    Oxygen signaling is critical for stem cell regulation, and oxidative stress-induced stem cell apoptosis decreases the efficiency of stem cell therapy. Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. Our study investigated the role of O-GlcNAcylation via glucosamine in the protection of hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs). Hypoxia increased mESCs apoptosis in a time-dependent manner. Moreover, hypoxia also slightly increased the O-GlcNAc level. Glucosamine treatment further enhanced the O-GlcNAc level and prevented hypoxia-induced mESC apoptosis, which was suppressed by O-GlcNAc transferase inhibitors. In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). In addition, glucosamine-increased O-GlcNAcylation of Sp1, which subsequently leads to Sp1 nuclear translocation and GPAT1 expression. Silencing of GPAT1 by gpat1 siRNA transfection reduced glucosamine-mediated anti-apoptosis in mESCs and reduced mammalian target of rapamycin (mTOR) phosphorylation. Indeed, LPA prevented mESCs from undergoing hypoxia-induced apoptosis and increased phosphorylation of mTOR and its substrates (S6K1 and 4EBP1). Moreover, mTOR inactivation by rapamycin (mTOR inhibitor) increased pro-apoptotic proteins expressions and mESC apoptosis. Furthermore, transplantation of non-targeting siRNA and glucosamine-treated mESCs increased cell survival and inhibited flap necrosis in mouse skin flap model. Conversely, silencing of GPAT1 expression reversed those glucosamine effects. In conclusion, enhancing O-GlcNAcylation of Sp1 by glucosamine stimulates GPAT1 expression, which leads to inhibition of hypoxia-induced mESC apoptosis via mTOR activation. PMID:27010859

  7. Regulation of cholesterol homeostasis

    NARCIS (Netherlands)

    van der Wulp, Mariette Y. M.; Verkade, Henkjan J.; Groen, Albert K.

    2013-01-01

    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-codin

  8. Characterization of placental cholesterol transport

    DEFF Research Database (Denmark)

    Lindegaard, Marie L; Wassif, Christopher A; Vaisman, Boris;

    2008-01-01

    cholesterol, in utero treatment with TO901317 resulted in increased cholesterol content in Dhcr7(-/-) embryos. Our data support the hypothesis that Abca1, and possibly Sr-b1, contributes to transport maternal cholesterol to the developing fetus. Furthermore, we show, as a proof of principle, that modulating......Patients with Smith-Lemli-Opitz syndrome (SLOS) are born with multiple congenital abnormalities. Postnatal cholesterol supplementation is provided; however, it cannot correct developmental malformations due to in utero cholesterol deficit. Increased transport of cholesterol from maternal to fetal...... embryonic days 13.5 and 18.5 in placental tissue; whereas, Sr-b1 expression decreased. To examine the functional role of Abca1, Abcg1 and Sr-b1 we measured the maternal-fetal transfer of (14)C-cholesterol in corresponding mutant embryos. Disruption of either Abca1 or Sr-b1 decreased cholesterol transfer by...

  9. What Your Cholesterol Levels Mean

    Science.gov (United States)

    ... Blood Pressure Tools & Resources Stroke More What Your Cholesterol Levels Mean Updated:Aug 9,2016 How’s your ... the Terms and Conditions and Privacy Policy Interactive Cholesterol Guide Find videos, trackers and more with our ...

  10. Effects of dietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones.

    OpenAIRE

    Kern, F

    1994-01-01

    We examined changes in cholesterol and bile acid metabolism produced by dietary cholesterol in gallstone subjects and matched controls. Healthy women were recruited and, after confirming the presence or absence of radiolucent gallstones, they were studied on regular diets and again on the same diet supplemented with five eggs daily for 15-18 d. Studies included plasma lipids, lipoproteins and apolipoproteins, dietary records, cholesterol absorption, cholesterol synthesis, plasma clearance of ...

  11. Lysosomes, cholesterol and atherosclerosis

    OpenAIRE

    Jerome, W. Gray

    2010-01-01

    Cholesterol-engorged macrophage foam cells are a critical component of the atherosclerotic lesion. Reducing the sterol deposits in lesions reduces clinical events. Sterol accumulations within lysosomes have proven to be particularly hard to mobilize out of foam cells. Moreover, excess sterol accumulation in lysosomes has untoward effects, including a complete disruption of lysosome function. Recently, we demonstrated that treatment of sterol-engorged macrophages in culture with triglyceride-c...

  12. Importance of macrophage cholesterol content on the flux of cholesterol mass

    OpenAIRE

    Sankaranarayanan, Sandhya; de la Llera-Moya, Margarita; Drazul-Schrader, Denise; Asztalos, Bela F.; Weibel, Ginny L.; Rothblat, George H.

    2010-01-01

    Net flux of cholesterol represents the difference between efflux and influx and can result in net cell-cholesterol accumulation, net cell-cholesterol depletion, or no change in cellular cholesterol content. We measured radiolabeled cell-cholesterol efflux and cell-cholesterol mass using cholesterol-normal and -enriched J774 and elicited mouse peritoneal macrophage cells. Net cell-cholesterol effluxes were observed when cholesterol-enriched J774 cells were incubated with 3.5% apolipoprotein (a...

  13. Cholesterol Embolism: An Overlooked Diagnosis

    Directory of Open Access Journals (Sweden)

    Sinem Nihal ESATOĞLU

    2012-01-01

    Full Text Available Acute renal failure following angiography is usually due to radiocontrast nephropathy; however, cholesterol embolism should be kept in mind when making the differential diagnosis. Cholesterol embolism is a multisystem disease, usually seen in elderly men who have severe atherosclerosis. In this case report, we describe a patient with cholesterol embolism who had a typical clinical history of progressive renal failure. We hope that this case report will emphasize the importance of this overlooked syndrome.

  14. Reducing Cholesterol Intake: Are the recommendations valid?

    OpenAIRE

    Chan, Joanna K.; McDonald, Bruce E.

    1991-01-01

    The authors question dietary recommendations for the general public calling for reduced cholesterol intake. Metabolic studies have shown that dietary cholesterol normally induces only small increases in blood cholesterol level. There is evidence that only a portion of the population responds to a change in cholesterol intake; hence lowering dietary cholesterol will be effective for only some.

  15. Inhibition of pancreatic cholesterol esterase reduces cholesterol absorption in the hamster

    OpenAIRE

    Heidrich, John E.; Contos, Linda M; Hunsaker, Lucy A; Deck, Lorraine M.; Vander Jagt, David L.

    2004-01-01

    Background Pancreatic cholesterol esterase has three proposed functions in the intestine: 1) to control the bioavailability of cholesterol from dietary cholesterol esters; 2) to contribute to incorporation of cholesterol into mixed micelles; and 3) to aid in transport of free cholesterol to the enterocyte. Inhibitors of cholesterol esterase are anticipated to limit the absorption of dietary cholesterol. Results The selective and potent cholesterol esterase inhibitor 6-chloro-3-(1-ethyl-2-cycl...

  16. Epigenetic Regulation of Cholesterol Homeostasis

    Directory of Open Access Journals (Sweden)

    Steve eMeaney

    2014-09-01

    Full Text Available Although best known as a risk factor for cardiovascular disease, cholesterol is a vital component of all mammalian cells. In addition to key structural roles, cholesterol is a vital biochemical precursor for numerous biologically important compounds including oxysterols and bile acids, as well as acting as an activator of critical morphogenic systems (e.g. the Hedgehog system. A variety of sophisticated regulatory mechanisms interact to coordinate the overall level of cholesterol in cells, tissues and the entire organism. Accumulating evidence indicates that in additional to the more ‘traditional’ regulatory schemes, cholesterol homeostasis is also under the control of epigenetic mechanisms such as histone acetylation and DNA methylation. The available evidence supporting a role for these mechanisms in the control of cholesterol synthesis, elimination, transport and storage are the focus of this review.

  17. Understand Your Risk for High Cholesterol

    Science.gov (United States)

    ... Resources Stroke More Understand Your Risk for High Cholesterol Updated:Apr 1,2016 LDL (bad) cholesterol is ... content was last reviewed on 04/21/2014. Cholesterol Guidelines: Putting the pieces together Myth vs. Truth – ...

  18. Overview of Cholesterol and Lipid Disorders

    Science.gov (United States)

    ... Medical Dictionary Additional Content Medical News Overview of Cholesterol and Lipid Disorders By Anne Carol Goldberg, MD ... Version. DOCTORS: Click here for the Professional Version Cholesterol Disorders Overview of Cholesterol and Lipid Disorders Dyslipidemia ...

  19. Cholesterol - what to ask your doctor

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000211.htm Cholesterol - what to ask your doctor To use the ... this page, please enable JavaScript. Your body needs cholesterol to work properly. When you have extra cholesterol ...

  20. A relation between high-density-lipoprotein cholesterol and bile cholesterol saturation.

    OpenAIRE

    Thornton, J R; Heaton, K. W.; Macfarlane, D G

    1981-01-01

    The association of cholesterol gall stones with coronary artery disease is controversial. To investigate this possible relation at the biochemical level, bile cholesterol saturation and the plasma concentrations of triglycerides, total cholesterol, and high-density-lipoprotein cholesterol (HDL cholesterol) were measured in 25 healthy, middle-aged women. Bile cholesterol saturation index was negatively correlated with HDL cholesterol. It was positively correlated with plasma triglycerides and ...

  1. Imaging appearances of cholesterol pneumonia

    International Nuclear Information System (INIS)

    Objection: To analyze the imaging appearances of cholesterol pneumonia. Methods We retrospectively analyzed the X-ray and CT findings of 3 patients with cholesterol pneumonia confirmed pathologically and reviewed correlative literature. Results: Lesions similar to mass were found in X-ray and CT imaging of three cases. Two of them appeared cavity with fluid-level and one showed multiple ring enhancement after CT contrast. The course of disease was very. long and it had no respond to antibiotic therapy. Amounts of foam cells rich in cholesterol crystal were detected in pathological examination. Conclusions: Cholesterol pneumonia is a rare chronic pulmonary idiopathic disease, and the radiological findings can do some help to its diagnosis. (authors)

  2. Cholesterol's location in lipid bilayers.

    Science.gov (United States)

    Marquardt, Drew; Kučerka, Norbert; Wassall, Stephen R; Harroun, Thad A; Katsaras, John

    2016-09-01

    It is well known that cholesterol modifies the physical properties of lipid bilayers. For example, the much studied liquid-ordered Lo phase contains rapidly diffusing lipids with their acyl chains in the all trans configuration, similar to gel phase bilayers. Moreover, the Lo phase is commonly associated with cholesterol-enriched lipid rafts, which are thought to serve as platforms for signaling proteins in the plasma membrane. Cholesterol's location in lipid bilayers has been studied extensively, and it has been shown - at least in some bilayers - to align differently from its canonical upright orientation, where its hydroxyl group is in the vicinity of the lipid-water interface. In this article we review recent works describing cholesterol's location in different model membrane systems with emphasis on results obtained from scattering, spectroscopic and molecular dynamics studies. PMID:27056099

  3. Cholesterol confusion and statin controversy.

    Science.gov (United States)

    DuBroff, Robert; de Lorgeril, Michel

    2015-07-26

    The role of blood cholesterol levels in coronary heart disease (CHD) and the true effect of cholesterol-lowering statin drugs are debatable. In particular, whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently, the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes, cancer, and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary, we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD. PMID:26225201

  4. to HDL-cholesterol functionality

    Directory of Open Access Journals (Sweden)

    Malara Marzena

    2016-05-01

    Full Text Available The purpose of this study was to analyse the scientific evidence concerning the effects of two enzymes – paraoxonase 1 and myeloperoxidase – on the functions of HDL-cholesterol. It is well documented that disturbed circulating lipoproteins (a high total and high LDL-cholesterol, and low HDL-cholesterol bring about atherosclerosis and an increased risk of cardiovascular disease (CVD which is recognised as the main cause of death all around the world. In consequence, numerous studies have focused on procedures which will improve the plasma lipoproteins profile by decreasing the total cholesterol and the LDL-cholesterol (LDL-C and increasing the HDL-cholesterol (HDL-C. However, the anti-atherogenic role of HDL-C has been challenged in studies showing that genetically elevated HDL-cholesterol does not offer protection against CVD. Moreover, it has been found that raising the circulating HDL-cholesterol fails to reduce atherosclerosis. The doubts concerning the protective role of HDL-C have been supported by in vitro studies which indicate that the HDL-C from patients with atherosclerosis does not have a protective action, but does stimulate inflammation and free radical synthesis. The above data suggests that HDL-C, commonly recognised as protective against atherosclerosis, in some circumstances becomes pro-atherogenic, and is thus dysfunctional. Our review focuses on two enzymes – paraoxonase 1 (PON1 and myeloperoxidase (MPO – which markedly affect the properties of HDL-C and contribute to its anti – or pro-atherogenic activity. Moreover, the effects of the diet and physical activity on PON1 and MPO are summarised with respect to the HDL-C functionality.

  5. Cholesterol Worships a New Idol

    Institute of Scientific and Technical Information of China (English)

    Ira G. Schulman

    2009-01-01

    The growing worldwide epidemic of cardiovascular disease suggests that new therapeutic strategies are needed to complement statins in the lowering of cholesterol levels. In a recent paper in Science, Tontonoz and colleagues have identified Idol as a protein that can control cholesterol levels by regulating the stability of the low-density lipoprotein receptor; inhibiting the activity of Idol could provide novel approaches for the treatment of cardiovascular disease.

  6. Cholesterol and benign prostate disease.

    Science.gov (United States)

    Freeman, Michael R; Solomon, Keith R

    2011-01-01

    The origins of benign prostatic diseases, such as benign prostatic hyperplasia (BPH) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), are poorly understood. Patients suffering from benign prostatic symptoms report a substantially reduced quality of life, and the relationship between benign prostate conditions and prostate cancer is uncertain. Epidemiologic data for BPH and CP/CPPS are limited, however an apparent association between BPH symptoms and cardiovascular disease (CVD) has been consistently reported. The prostate synthesizes and stores large amounts of cholesterol and prostate tissues may be particularly sensitive to perturbations in cholesterol metabolism. Hypercholesterolemia, a major risk factor for CVD, is also a risk factor for BPH. Animal model and clinical trial findings suggest that agents that inhibit cholesterol absorption from the intestine, such as the class of compounds known as polyene macrolides, can reduce prostate gland size and improve lower urinary tract symptoms (LUTS). Observational studies indicate that cholesterol-lowering drugs reduce the risk of aggressive prostate cancer, while prostate cancer cell growth and survival pathways depend in part on cholesterol-sensitive biochemical mechanisms. Here we review the evidence that cholesterol metabolism plays a role in the incidence of benign prostate disease and we highlight possible therapeutic approaches based on this concept. PMID:21862201

  7. Formation of Cholesterol Bilayer Domains Precedes Formation of Cholesterol Crystals in Cholesterol/Dimyristoylphosphatidylcholine Membranes: EPR and DSC Studies

    OpenAIRE

    Mainali, Laxman; Raguz, Marija; Subczynski, Witold K.

    2013-01-01

    Saturation-recovery EPR along with DSC were used to determine the cholesterol content at which pure cholesterol bilayer domains (CBDs) and cholesterol crystals begin to form in dimyristoylphosphatidylcholine (DMPC) membranes. To preserve compositional homogeneity throughout the membrane suspension, lipid multilamellar dispersions were prepared using a rapid solvent exchange method. The cholesterol content increased from 0 to 75 mol%. With spin-labeled cholesterol analogs it was shown that the...

  8. Phosphatidylcholine: Greasing the Cholesterol Transport Machinery

    Science.gov (United States)

    Lagace, Thomas A.

    2015-01-01

    Negative feedback regulation of cholesterol metabolism in mammalian cells ensures a proper balance of cholesterol with other membrane lipids, principal among these being the major phospholipid phosphatidylcholine (PC). Processes such as cholesterol biosynthesis and efflux, cholesteryl ester storage in lipid droplets, and uptake of plasma lipoproteins are tuned to the cholesterol/PC ratio. Cholesterol-loaded macrophages in atherosclerotic lesions display increased PC biosynthesis that buffers against elevated cholesterol levels and may also facilitate cholesterol trafficking to enhance cholesterol sensing and efflux. These same mechanisms could play a generic role in homeostatic responses to acute changes in membrane free cholesterol levels. Here, I discuss the established and emerging roles of PC metabolism in promoting intracellular cholesterol trafficking and membrane lipid homeostasis. PMID:27081313

  9. Cholesterol confusion and statin controversy

    Institute of Scientific and Technical Information of China (English)

    Robert; Du; Broff; Michel; de; Lorgeril

    2015-01-01

    The role of blood cholesterol levels in coronary heart disease(CHD) and the true effect of cholesterollowering statin drugs are debatable. In particular,whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently,the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes,cancer,and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary,we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD.

  10. Effect of cholesterol oxidation products on cholesterol metabolism in the laying hen.

    Science.gov (United States)

    Naber, E C; Allred, J B; Winget, C J; Stock, A E

    1985-04-01

    Two experiments were conducted to determine the effect of purified cholesterol and oxidized cholesterol in the diet of the laying hen on egg production characteristics, in vitro - in ovo utilization of acetate for cholesterol biosynthesis, and the activity of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in biosynthesis of cholesterol. Previous work has demonstrated inhibition of cholesterol synthesis by cholesterol oxides in tissue culture cells but not in hepatic tissues of animals through dietary administration. Feeding .5% of either purified or oxidized cholesterol had no effect on egg production, egg weight, body weight, or diet consumption. In both experiments egg yolk cholesterol was significantly increased by both cholesterol sources, but eggs from hens fed oxidized cholesterol had lower cholesterol contents than those from hens fed purified cholesterol. Relative utilization of acetate for cholesterol biosynthesis was significantly reduced by feeding both cholesterol sources. Hepatic enzyme activity measured by production of mevalonic acid was significantly inhibited by feeding purified cholesterol. A further significant reduction in enzyme activity was observed when oxidized cholesterol was fed, indicating that dietary cholesterol oxides are much more potent than purified cholesterol in limiting the activity of the enzyme. PMID:4001052

  11. Polarizable multipolar electrostatics for cholesterol

    Science.gov (United States)

    Fletcher, Timothy L.; Popelier, Paul L. A.

    2016-08-01

    FFLUX is a novel force field under development for biomolecular modelling, and is based on topological atoms and the machine learning method kriging. Successful kriging models have been obtained for realistic electrostatics of amino acids, small peptides, and some carbohydrates but here, for the first time, we construct kriging models for a sizeable ligand of great importance, which is cholesterol. Cholesterol's mean total (internal) electrostatic energy prediction error amounts to 3.9 kJ mol-1, which pleasingly falls below the threshold of 1 kcal mol-1 often cited for accurate biomolecular modelling. We present a detailed analysis of the error distributions.

  12. [Attitude of blood donors towards cholesterol measurement].

    Science.gov (United States)

    Flesland, O; Botten, G; Solheim, B G; Orjasaeter, H

    1992-05-20

    In analyses of cost-effectiveness it is customary to count knowledge of having a high serum cholesterol level as a negative factor. There is little support for this practice in the literature. We have studied the attitude of 305 Norwegian blood donors towards cholesterol testing. 63% stated that they were interested in their serum cholesterol level, and 40% said they knew their own serum cholesterol level. The attitude towards cholesterol testing was clearly positive, both among men and among women, regardless of age. Only one donor stated that she did not want to have her serum cholesterol tested in conjunction with blood donation. PMID:1509430

  13. The ABC of cholesterol transport

    NARCIS (Netherlands)

    Plösch, Torsten

    2004-01-01

    Cholesterol fulfills an indispensable role in mammalian physiology. It is an important constituent of all cell membranes. Furthermore, it is the precursor of steroid hormones, which regulate a variety of physiological functions, and of bile salts, which are necessary for the generation of bile flow

  14. Membrane Cholesterol Modulates Superwarfarin Toxicity.

    Science.gov (United States)

    Marangoni, M Natalia; Martynowycz, Michael W; Kuzmenko, Ivan; Braun, David; Polak, Paul E; Weinberg, Guy; Rubinstein, Israel; Gidalevitz, David; Feinstein, Douglas L

    2016-04-26

    Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions with amphiphilic membranes and modulation of biological responses. We find that superwarfarins brodifacoum and difenacoum increase lactate production and cell death in neuroblastoma cells. In contrast, neither causes changes in glioma cells that have higher cholesterol content. After choleterol depletion, lactate production was increased and cell viability was reduced. Drug-membrane interactions were examined by surface X-ray scattering using Langmuir monolayers of dipalmitoylphosphatidylcholine and/or cholesterol. Specular X-ray reflectivity data revealed that superwarfarins, but not warfarin, intercalate between dipalmitoylphosphatidylcholine molecules, whereas grazing incidence X-ray diffraction demonstrated changes in lateral crystalline order of the film. Neither agent showed significant interactions with monolayers containing >20% cholesterol. These findings demonstrate an affinity of superwarfarins to biomembranes and suggest that cellular responses to these agents are regulated by cholesterol content. PMID:27119638

  15. Membrane Cholesterol Modulates Superwarfarin Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Marangoni, M. Natalia; Martynowycz, Michael W.; Kuzmenko, Ivan; Braun, David; Polak, Paul E.; Weinberg, Guy; Rubinstein, Israel; Gidalevitz, David; Feinstein, Douglas L.

    2016-04-26

    Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions with amphiphilic membranes and modulation of biological responses. We find that superwarfarins brodifacoum and difenacoum increase lactate production and cell death in neuroblastoma cells. In contrast, neither causes changes in glioma cells that have higher cholesterol content. After choleterol depletion, lactate production was increased and cell viability was reduced. Drug-membrane interactions were examined by surface X-ray scattering using Langmuir monolayers of dipalmitoylphosphatidylcholine and/or cholesterol. Specular X-ray reflectivity data revealed that superwarfarins, but not warfarin, intercalate between dipalmitoylphosphatidylcholine molecules, whereas grazing incidence X-ray diffraction demonstrated changes in lateral crystalline order of the film. Neither agent showed significant interactions with monolayers containing >20% cholesterol. These findings demonstrate an affinity of superwarfarins to biomembranes and suggest that cellular responses to these agents are regulated by cholesterol content.

  16. Active membrane cholesterol as a physiological effector.

    Science.gov (United States)

    Lange, Yvonne; Steck, Theodore L

    2016-09-01

    Sterols associate preferentially with plasma membrane sphingolipids and saturated phospholipids to form stoichiometric complexes. Cholesterol in molar excess of the capacity of these polar bilayer lipids has a high accessibility and fugacity; we call this fraction active cholesterol. This review first considers how active cholesterol serves as an upstream regulator of cellular sterol homeostasis. The mechanism appears to utilize the redistribution of active cholesterol down its diffusional gradient to the endoplasmic reticulum and mitochondria, where it binds multiple effectors and directs their feedback activity. We have also reviewed a broad literature in search of a role for active cholesterol (as opposed to bulk cholesterol or lipid domains such as rafts) in the activity of diverse membrane proteins. Several systems provide such evidence, implicating, in particular, caveolin-1, various kinds of ABC-type cholesterol transporters, solute transporters, receptors and ion channels. We suggest that this larger role for active cholesterol warrants close attention and can be tested easily. PMID:26874289

  17. Do You Know Your Cholesterol Levels?

    Science.gov (United States)

    ... The Health Information Center Do You Know Your Cholesterol Levels? Print-friendly Version (PDF, 6.1 MB) ... Eat Smart Did you know that high blood cholesterol is a serious problem among Latinos? About one ...

  18. Cerebral cholesterol granuloma in homozygous familial hypercholesterolemia

    OpenAIRE

    Francis, Gordon A; Johnson, Royce L.; Findlay, J. Max; Wang, Jian; Hegele, Robert A.

    2005-01-01

    Familial hypercholesterolemia (FH) is characterized by the accumulation of excess cholesterol in tissues including the artery wall and tendons. We describe a patient with homozygous FH who presented with asymptomatic cholesterol granuloma of the brain. The patient's plasma low-density lipoprotein cholesterol level was remarkably responsive to combination hypolipidemic therapy with statin plus ezetimibe. This case illustrates another potential complication of whole-body cholesterol excess and ...

  19. Quercetin regulates hepatic cholesterol metabolism by promoting cholesterol-to-bile acid conversion and cholesterol efflux in rats.

    Science.gov (United States)

    Zhang, Min; Xie, Zongkai; Gao, Weina; Pu, Lingling; Wei, Jingyu; Guo, Changjiang

    2016-03-01

    Quercetin, a common member of the flavonoid family, is widely present in plant kingdom. Despite that quercetin is implicated in regulating cholesterol metabolism, the molecular mechanism is poorly understood. We hypothesized that quercetin regulates cholesterol homeostasis through regulating the key enzymes involved in hepatic cholesterol metabolism. To test this hypothesis, we compared the profile of key enzymes and transcription factors involved in the hepatic cholesterol metabolism in rats with or without quercetin supplementation. Twenty male Wistar rats were randomly divided into control and quercetin-supplemented groups. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids in feces and bile were measured. Hepatic enzymatic activities were determined by activity assay kit and high-performance liquid chromatography-based analyses. The messenger RNA (mRNA) and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. The results showed that the activity of hepatic cholesterol 7α-hydroxylase, a critical enzyme in the conversion of cholesterol to bile acids, was significantly elevated by quercetin. The expression of cholesterol 7α-hydroxylase, as well as liver X receptor α, an important transcription factor, was also increased at both mRNA and protein levels by quercetin. However, quercetin exposure had no impact on the activity of hepatic HMG-CoA reductase, a rate-limiting enzyme in the biosynthesis of cholesterol. We also found that quercetin treatment significantly increased ATP binding cassette transporter G1 mRNA and protein expression in the liver, suggesting that quercetin may increase hepatic cholesterol efflux. Collectively, the results presented here indicate that quercetin regulates hepatic cholesterol metabolism mainly through the pathways that promote cholesterol-to-bile acid conversion and

  20. High Cholesterol: Medicines to Help You

    Science.gov (United States)

    ... risks of taking these medicines. Talk to your doctor or pharmacist about all of the risks of taking your ... 20 should have their cholesterol checked by a doctor. Most people do not show ... Good vs. Bad Cholesterol Not all cholesterol in your blood ...

  1. Isolation of Cholesterol from an Egg Yolk

    Science.gov (United States)

    Taber, Douglass F.; Li, Rui; Anson, Cory M.

    2011-01-01

    A simple procedure for the isolation of the cholesterol, by hydrolysis and extraction followed by column chromatography, is described. The cholesterol can be further purified by complexation with oxalic acid. It can also be oxidized and conjugated to cholestenone. The source of the cholesterol is one egg yolk, which contains about 200 mg of…

  2. Intestinal cholesterol secretion : future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  3. Remnant cholesterol and ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G

    2014-01-01

    PURPOSE OF REVIEW: To review recent advances in the field of remnant cholesterol as a contributor to the development of ischemic heart disease (IHD). RECENT FINDINGS: Epidemiologic, mechanistic, and genetic studies all support a role for elevated remnant cholesterol (=cholesterol in triglyceride...

  4. Study on Cholesterol Renewal of Fatty Livers by Means of Tritiated Cholesterol

    International Nuclear Information System (INIS)

    It is known that ingestion by rats of a diet rich in cholesterol (2%) results in the formation of cholesterol-fatty liver. In the experiment, animals so fed for periods of one to three months were made to ingest the same diet in which the cholesterol had been replaced by tritiated cholesterol of known specific radioactivity. The rats were sacrificed after various ingestion periods up to a maximum of 51 d. Examination of the specific radioactivities of liver and serum cholesterol, free and esterified, gave the same values. Hence, the cholesterol of cholesterol-fatty livers is entirely renewed and does not represent an inert mass in the liver. (author)

  5. Non-cholesterol sterols and cholesterol metabolism in sitosterolemia.

    Science.gov (United States)

    Othman, Rgia A; Myrie, Semone B; Jones, Peter J H

    2013-12-01

    Sitosterolemia (STSL) is a rare autosomal recessive disease, manifested by extremely elevated plant sterols (PS) in plasma and tissue, leading to xanthoma and premature atherosclerotic disease. Therapeutic approaches include limiting PS intake, interrupting enterohepatic circulation of bile acid using bile acid binding resins such as cholestyramine, and/or ileal bypass, and inhibiting intestinal sterol absorption by ezetimibe (EZE). The objective of this review is to evaluate sterol metabolism in STSL and the impact of the currently available treatments on sterol trafficking in this disease. The role of PS in initiation of xanthomas and premature atherosclerosis is also discussed. Blocking sterols absorption with EZE has revolutionized STSL patient treatment as it reduces circulating levels of non-cholesterol sterols in STSL. However, none of the available treatments including EZE have normalized plasma PS concentrations. Future studies are needed to: (i) explore where cholesterol and non-cholesterol sterols accumulate, (ii) assess to what extent these sterols in tissues can be mobilized after blocking their absorption, and (iii) define the factors governing sterol flux. PMID:24267242

  6. Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

    KAUST Repository

    Mandal, Pritam

    2016-06-01

    Cholesterol is crucial to the mechanical properties of cell membranes that are important to cells’ behavior. Its depletion from the cell membranes could be dramatic. Among cyclodextrins (CDs), methyl beta cyclodextrin (MβCD) is the most efficient to deplete cholesterol (Chol) from biomembranes. Here, we focus on the depletion of cholesterol from a C16 ceramide/cholesterol (C16-Cer/Chol) mixed monolayer using MβCD. While the removal of cholesterol by MβCD depends on the cholesterol concentration in most mixed lipid monolayers, it does not depend very much on the concentration of cholesterol in C16-Cer/Chol monolayers. The surface pressure decay during depletion were described by a stretched exponential that suggested that the cholesterol molecules are unable to diffuse laterally and behave like static traps for the MβCD molecules. Cholesterol depletion causes morphology changes of domains but these disrupted monolayers domains seem to reform even when cholesterol level was low.

  7. How cholesterol homeostasis is regulated by plasma membrane cholesterol in excess of phospholipids

    OpenAIRE

    Lange, Yvonne; Ye, Jin; Steck, Theodore L.

    2004-01-01

    How do cells sense and control their cholesterol levels? Whereas most of the cell cholesterol is located in the plasma membrane, the effectors of its abundance are regulated by a small pool of cholesterol in the endoplasmic reticulum (ER). The size of the ER compartment responds rapidly and dramatically to small changes in plasma membrane cholesterol around the normal level. Consequently, increasing plasma membrane cholesterol in vivo from just below to just above the basal level evoked an ac...

  8. Endogenous cholesterol synthesis, fecal steroid excretion and serum lanosterol in subjects with high or low response of serum cholesterol to dietary cholesterol

    OpenAIRE

    A. C. Beynen; Katan, M B; Gent, van, H.

    1986-01-01

    In this study we addressed the question whether hypo- and hyper-responders to dietary cholesterol differ with regard to the flexibility of endogenous cholesterol synthesis after changes in cholesterol intake. Whole-body cholesterol synthesis was measured as faecal excretion of neutral steroids and bile acids minus cholesterol intake. In addition, we determined serum concentrations of lanosterol, a precursor of cholesterol and a possible indicator of cholesterol biosynthetic activity. The stud...

  9. Epididymis cholesterol homeostasis and sperm fertilizing ability

    Institute of Scientific and Technical Information of China (English)

    Fabrice Saez; Aurélia Ouvrier; Jo(e)l R Drevet

    2011-01-01

    Cholesterol, being the starting point of steroid hormone synthesis, is a long known modulator of both female and male reproductive physiology especially at the level of the gonads and the impact cholesterol has on gametogenesis. Less is known about the effects cholesterol homeostasis may have on postgonadic reproductive functions. Lately, several data have been reported showing how imbalanced cholesterol levels may particularly affect the post-testicular events of sperm maturation that lead to fully fertile male gametes. This review will focus on that aspect and essentially centers on how cholesterol is important for the physiology of the mammalian epididymis and spermatozoa.

  10. Peptide mediators of cholesterol efflux

    Science.gov (United States)

    Bielicki, John K.; Johansson, Jan

    2013-04-09

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  11. Trapping crystal nucleation of cholesterol monohydrate

    DEFF Research Database (Denmark)

    Solomonov, I.; Weygand, M.J.; Kjær, K.; Rapaport, H.; Leiserowitz, L.

    2005-01-01

    Crystalline nucleation of cholesterol at the air-water interface has been studied via grazing incidence x-ray diffraction using synchrotron radiation. The various stages of cholesterol molecular assembly from monolayer to three bilayers incorporating interleaving hydrogen-bonded water layers in a...... least initially, an intralayer cholesterol rearrangement in a single-crystal-to-single-crystal transition. The preferred nucleation of the monoclinic phase of cholesterol . H2O followed by transformation to the stable monohydrate phase may be associated with an energetically more stable cholesterol...... bilayer arrangement of the former and a more favorable hydrogen-bonding arrangement of the latter. The relevance of this nucleation process of cholesterol monohydrate to pathological crystallization of cholesterol from cell biomembranes is discussed....

  12. The Role of Cholesterol in Cancer.

    Science.gov (United States)

    Kuzu, Omer F; Noory, Mohammad A; Robertson, Gavin P

    2016-04-15

    The roles played by cholesterol in cancer development and the potential of therapeutically targeting cholesterol homeostasis is a controversial area in the cancer community. Several epidemiologic studies report an association between cancer and serum cholesterol levels or statin use, while others suggest that there is not one. Furthermore, the Cancer Genome Atlas (TCGA) project using next-generation sequencing has profiled the mutational status and expression levels of all the genes in diverse cancers, including those involved in cholesterol metabolism, providing correlative support for a role of the cholesterol pathway in cancer development. Finally, preclinical studies tend to more consistently support the role of cholesterol in cancer, with several demonstrating that cholesterol homeostasis genes can modulate development. Because of space limitations, this review provides selected examples of the epidemiologic, TCGA, and preclinical data, focusing on alterations in cholesterol homeostasis and its consequent effect on patient survival. In melanoma, this focused analysis demonstrated that enhanced expression of cholesterol synthesis genes was associated with decreased patient survival. Collectively, the studies in melanoma and other cancer types suggested a potential role of disrupted cholesterol homeostasis in cancer development but additional studies are needed to link population-based epidemiological data, the TCGA database results, and preclinical mechanistic evidence to concretely resolve this controversy. Cancer Res; 76(8); 2063-70. ©2016 AACR. PMID:27197250

  13. The phase behavior of hydrated cholesterol.

    Science.gov (United States)

    Loomis, C R; Shipley, G G; Small, D M

    1979-05-01

    The thermotropic phase behavior of cholesterol monohydrate in water was investigated by differential scanning calorimetry, polarizing light microscopy, and x-ray diffraction. In contrast to anhydrous cholesterol which undergoes a polymorphic crystalline transition at 39 degrees C and a crystalline to liquid transition at 151 degrees C, the closed system of cholesterol monohydrate and water exhibited three reversible endothermic transitions at 86, 123, and 157 degrees C. At 86 degrees C, cholesterol monohydrate loses its water of hydration, forming the high temperature polymorph of anhydrous cholesterol. At least 24 hours were required for re-hydration of cholesterol and the rate of hydration was dependent on the polymorphic crystalline form of anhydrous cholesterol. At 123 degrees C, anhydrous crystalline cholesterol in the presence of excess water undergoes a sharp transition to a birefringent liquid crystalline phase of smectic texture. The x-ray diffraction pattern obtained from this phase contained two sharp low-angle reflections at 37.4 and 18.7 A and a diffuse wide-angle reflection centered at 5.7 A, indicating a layered smectic type of liquid crystalline structure with each layer being two cholesterol molecules thick. The liquid crystalline phase is stable over the temperature range of 123 to 157 degrees C before melting to a liquid dispersed in water. The observation of a smectic liquid crystalline phase for hydrated cholesterol correlates with its high surface activity and helps to explain its ability to exist in high concentrations in biological membranes. PMID:458269

  14. Biliary cholesterol secretion: More than a simple ABC

    Institute of Scientific and Technical Information of China (English)

    Arne; Dikkers; Uwe; JF; Tietge

    2010-01-01

    Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the f inal step for the elimination of cholesterol originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the main pathophys...

  15. CHOLESTEROL ASSIMILATION BY COMMERCIAL YOGHURT STARTER CULTURES

    OpenAIRE

    Małgorzata Ziarno; Ewa Sękul; Alvaro Aguado Lafraya

    2007-01-01

    The ability to in vitro cholesterol level reduction in laboratory media has been shown for numerous strains of lactic acid bacteria, but not for all strains of lactic bacteria used in the dairy industry. The aim of this work was the determination of the ability of selected thermophilic lactic acid bacteria to cholesterol assimilation during 24 h culture in MRS broth. Commercial starter cultures showed various ability to cholesterol assimilation from laboratory medium. In case of starter cultu...

  16. Structure of cholesterol/ceramide monolayer mixtures

    DEFF Research Database (Denmark)

    Scheffer, L.; Solomonov, I.; Weygand, M.J.; Kjær, K.; Leiserowitz, L.; Addadi, L.

    2005-01-01

    The structure of monolayers of cholesterol/ ceramide mixtures was investigated using grazing incidence x-ray diffraction, immunofluorescence, and atomic force microscopy techniques. Grazing incidence x-ray diffraction measurements showed the existence of a crystalline mixed phase of the two...... was determined and modeled. Immunolabeling was performed with an antibody specific to the cholesterol monohydrate crystalline arrangement. The antibody recognizes crystalline cholesterol monolayers, but does not interact with crystalline ceramide. Immunofluorescence and atomic force microscopy data...

  17. Structure of Cholesterol in Lipid Rafts

    Science.gov (United States)

    Toppozini, Laura; Meinhardt, Sebastian; Armstrong, Clare L.; Yamani, Zahra; Kučerka, Norbert; Schmid, Friederike; Rheinstädter, Maikel C.

    2014-11-01

    Rafts, or functional domains, are transient nano-or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking, and lipid or protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules, we observe raftlike structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to ordering of the cholesterol molecules in the raftlike structures were observed and indexed by two different structures: a monoclinic structure of ordered cholesterol pairs of alternating direction in equilibrium with cholesterol plaques, i.e., triclinic cholesterol bilayers.

  18. Lysobisphosphatidic acid controls endosomal cholesterol levels.

    Science.gov (United States)

    Chevallier, Julien; Chamoun, Zeina; Jiang, Guowei; Prestwich, Glenn; Sakai, Naomi; Matile, Stefan; Parton, Robert G; Gruenberg, Jean

    2008-10-10

    Most cell types acquire cholesterol by endocytosis of circulating low density lipoprotein, but little is known about the mechanisms of intra-endosomal cholesterol transport and about the primary cause of its aberrant accumulation in the cholesterol storage disorder Niemann-Pick type C (NPC). Here we report that lysobisphosphatidic acid (LBPA), an unconventional phospholipid that is only detected in late endosomes, regulates endosomal cholesterol levels under the control of Alix/AlP1, which is an LBPA-interacting protein involved in sorting into multivesicular endosomes. We find that Alix down-expression decreases both LBPA levels and the lumenal vesicle content of late endosomes. Cellular cholesterol levels are also decreased, presumably because the storage capacity of endosomes is affected and thus cholesterol clearance accelerated. Both lumenal membranes and cholesterol can be restored in Alix knockdown cells by exogenously added LBPA. Conversely, we also find that LBPA becomes limiting upon pathological cholesterol accumulation in NPC cells, because the addition of exogenous LBPA, but not of LBPA isoforms or analogues, partially reverts the NPC phenotype. We conclude that LBPA controls the cholesterol capacity of endosomes. PMID:18644787

  19. Potential of BODIPY-cholesterol for analysis of cholesterol transport and diffusion in living cells

    DEFF Research Database (Denmark)

    Wüstner, Daniel; Lund, Frederik Wendelboe; Röhrl, Clemens;

    2016-01-01

    Cholesterol is an abundant and important lipid component of cellular membranes. Analysis of cholesterol transport and diffusion in living cells is hampered by the technical challenge of designing suitable cholesterol probes which can be detected for example by optical microscopy. One strategy is to...... use intrinsically fluorescent sterols, as dehydroergosterol (DHE), having minimal chemical alteration compared to cholesterol but giving low fluorescence signals in the UV region of the spectrum. Alternatively, one can use dye-tagged cholesterol analogs and in particular BODIPY-cholesterol (BChol......), whose synthesis and initial characterization was pioneered by Robert Bittman. Here, we give a general overview of the properties and applications but also limitations of BODIPY-tagged cholesterol probes for analyzing intracellular cholesterol trafficking. We describe our own experiences and...

  20. Oxidised LDL, HDL cholesterol, LDL cholesterol levels in patients of coronary artery disease

    OpenAIRE

    Ghosh, Joya; T K Mishra; Rao, Y. N.; Aggarwal, S. K.

    2006-01-01

    Coronary artery disease is a major cause of morbidity and has various risk factors. Lipid profile i.e. low HDL-cholesterol, high LDL cholesterol, high total cholesterol, high triglycerides playing important role in its causation. Recently interest has been shown in the oxidized fraction of LDL as one of the risk factors. In the present study 60 age and sex matched normal healthy individuals were taken as controls and 60 patients of CAD were taken. Cholesterol was measured by enzymatic method,...

  1. Mast Cells and HDL Studies on Cholesterol Efflux and Reverse Cholesterol Transport

    OpenAIRE

    Kareinen, Ilona

    2015-01-01

    Atherosclerosis is an inflammatory disease characterized by the accumulation of cholesterol in the arterial intima and consequently the formation of atherosclerotic plaques. Formation of these plaques is initiated by the appearance of macrophage foam cell in the arterial intima. Foam cells are formed as excessive cholesterol accumulates in the cytosol of macrophages and finally the net influx exceeds the efflux of cholesterol. Excessive accumulation of chemically modified cholesterol in foam ...

  2. Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes

    OpenAIRE

    Storey, Stephen M.; McIntosh, Avery L.; Huang, Huan; Landrock, Kerstin K.; Martin, Gregory G.; Landrock, Danilo; Payne, H. Ross; Atshaves, Barbara P.; Kier, Ann B.; Schroeder, Friedhelm

    2012-01-01

    A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-af...

  3. Dietary cholesterol and fats at a young age : do they influence cholesterol metabolism in adult life?

    NARCIS (Netherlands)

    Temmerman, A M; Vonk, R J; Niezen-Koning, K; Berger, R.; Fernandes, J

    1989-01-01

    The effects of dietary cholesterol and fats on cholesterol metabolism later in life were studied in Mongolian gerbils. Three groups were given a basic diet with soybean oil, palm kernel oil amounting to 8.75% (w/w), or the basic diet only. In three other groups, cholesterol (0.05%) was added to the

  4. From blood to gut : Direct secretion of cholesterol via transintestinal cholesterol efflux

    NARCIS (Netherlands)

    Vrins, Carlos L. J.

    2010-01-01

    The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol lowering therapies By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body For a long time this removal via

  5. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W; Wolters, Justina C; Kuivenhoven, Jan Albert; Tietge, Uwe J.F.; Brufau Dones, Gemma; Groen, Albert K

    2016-01-01

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins we

  6. Inherited Cholesterol Disorder Significantly Boosts Heart Risks

    Science.gov (United States)

    ... leaves her cholesterol untreated, her risk of coronary heart disease death or nonfatal heart attack would be comparable to ... Recent Health News Related MedlinePlus Health Topics Cholesterol Heart Diseases--Prevention ... Us Get email updates Subscribe to RSS Follow us ...

  7. Computational model for monitoring cholesterol metabolism.

    Science.gov (United States)

    Selvakumar, R; Rashith Muhammad, M; Poornima Devi, G

    2014-12-01

    A non-deterministic finite automaton is designed to observe the cholesterol metabolism with the states of acceptance and rejection. The acceptance state of the automaton depicts the normal level of metabolism and production of good cholesterol as an end product. The rejection state of this machine shows the inhibition of enzymatic activity in cholesterol synthesis and removal of free fatty acids. The deficiency in human cholesterol metabolism pathway results in abnormal accumulation of cholesterol in plasma, arterial tissues leading to diseases such as hypercholesterolemia, atherosclerosis respectively and formation of gallstones. The designed machine can be used to monitor the cholesterol metabolism at molecular level through regulation of enzymes involved in the biosynthesis and metabolism of cholesterol for the treatment of diseases incident due to the respective metabolic disorder. In addition, an algorithm for this machine has been developed to compare the programmed string with the given string. This study demonstrates the construction of a machine that is used for the development of molecular targeted therapy for the disorders in cholesterol metabolism. PMID:26396654

  8. Cholesterol modulates bitter taste receptor function.

    Science.gov (United States)

    Pydi, Sai Prasad; Jafurulla, Md; Wai, Lisa; Bhullar, Rajinder P; Chelikani, Prashen; Chattopadhyay, Amitabha

    2016-09-01

    Bitter taste perception in humans is believed to act as a defense mechanism against ingestion of potential toxic substances. Bitter taste is perceived by 25 distinct bitter taste receptors (T2Rs) which belong to the family of G protein-coupled receptors (GPCRs). In the overall context of the role of membrane lipids in GPCR function, we show here that T2R4, a representative member of the bitter taste receptor family, displays cholesterol sensitivity in its signaling function. In order to gain further insight into cholesterol sensitivity of T2R4, we mutated two residues Tyr114(3.59) and Lys117(3.62) present in the cholesterol recognition amino acid consensus (CRAC) motif in T2R4 with alanines. We carried out functional characterization of the mutants by calcium mobilization, followed by cholesterol depletion and replenishment. CRAC motifs in GPCRs have previously been implicated in preferential cholesterol association. Our analysis shows that the CRAC motif represents an intrinsic feature of bitter taste receptors and is conserved in 22 out of 25 human T2Rs. We further demonstrate that Lys117, an important CRAC residue, is crucial in the reported cholesterol sensitivity of T2R4. Interestingly, cholesterol sensitivity of T2R4 was observed at quinine concentrations in the lower mM range. To the best of our knowledge, our results represent the first report addressing the molecular basis of cholesterol sensitivity in the function of taste receptors. PMID:27288892

  9. Biliary cholesterol excretion: A novel mechanism that regulates dietary cholesterol absorption

    OpenAIRE

    Sehayek, Ephraim; Ono, Jennie G.; Shefer, Sarah; Nguyen, Lien B.; Wang, Nan; Batta, Ashok K.; Salen, Gerald; Smith, Jonathan D.; Tall, Alan R.; Breslow, Jan L.

    1998-01-01

    The regulation of dietary cholesterol absorption was examined in C57BL/6 and transgenic mice with liver overexpression of the scavenger receptor BI (SR-BI Tg). In C57BL/6 animals, feeding 0.02 to 1% (wt/wt) dietary cholesterol resulted in a dose-dependent decrease in the percentage of dietary cholesterol absorbed. A plot of total daily mass of dietary cholesterol absorbed versus the percentage by weight of cholesterol in the diet yielded a curve suggesting a saturable process with a Km of 0.4...

  10. The Structure of Cholesterol in Lipid Rafts

    CERN Document Server

    Toppozini, Laura; Armstrong, Clare L; Yamani, Zahra; Kucerka, Norbert; Schmid, Friederike; Rheinstaedter, Maikel C

    2014-01-01

    Rafts, or functional domains, are transient nano- or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking and lipid/protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short-lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules we observe raft-like structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to orderin...

  11. Trapping crystal nucleation of cholesterol monohydrate

    DEFF Research Database (Denmark)

    Solomonov, I.; Weygand, M.J.; Kjær, K.;

    2005-01-01

    Crystalline nucleation of cholesterol at the air-water interface has been studied via grazing incidence x-ray diffraction using synchrotron radiation. The various stages of cholesterol molecular assembly from monolayer to three bilayers incorporating interleaving hydrogen-bonded water layers in a...... monoclinic cholesterol . H2O phase, has been monitored and their structures characterized to near atomic resolution. Crystallographic evidence is presented that this multilayer phase is similar to that of a reported metastable cholesterol phase of undetermined structure obtained from bile before...... transformation to the triclinic phase of cholesterol . H2O, the thermodynamically stable macroscopic form. According to grazing incidence x-ray diffraction measurements and crystallographic data, a transformation from the monoclinic film structure to a multilayer of the stable monohydrate phase involves, at...

  12. Major Risk Factors for Heart Disease: High Blood Cholesterol

    Science.gov (United States)

    ... Major Risk Factors for Heart Disease High Blood Cholesterol High blood cholesterol is another major risk factor for heart disease ... can do something about. The higher your blood cholesterol level, the greater your risk for developing heart ...

  13. High Blood Cholesterol: What You Need to Know

    Science.gov (United States)

    ... Audiences Contact The Health Information Center High Blood Cholesterol: What You Need To Know Table of Contents ... Lifestyle Changes (TLC) Drug Treatment Resources Why Is Cholesterol Important? Your blood cholesterol level has a lot ...

  14. Endogenous cholesterol synthesis, fecal steroid excretion and serum lanosterol in subjects with high or low response of serum cholesterol to dietary cholesterol

    NARCIS (Netherlands)

    Beynen, A.C.; Katan, M.B.; Gent, van C.M.

    1986-01-01

    In this study we addressed the question whether hypo- and hyper-responders to dietary cholesterol differ with regard to the flexibility of endogenous cholesterol synthesis after changes in cholesterol intake. Whole-body cholesterol synthesis was measured as faecal excretion of neutral steroids and b

  15. The Structural Basis of Cholesterol Accessibility in Membranes

    OpenAIRE

    Olsen, Brett N.; Bielska, Agata A.; Lee, Tiffany; Daily, Michael D.; Covey, Douglas F.; Schlesinger, Paul H.; Baker, Nathan A.; Ory, Daniel S.

    2013-01-01

    Although the majority of free cellular cholesterol is present in the plasma membrane, cholesterol homeostasis is principally regulated through sterol-sensing proteins that reside in the cholesterol-poor endoplasmic reticulum (ER). In response to acute cholesterol loading or depletion, there is rapid equilibration between the ER and plasma membrane cholesterol pools, suggesting a biophysical model in which the availability of plasma membrane cholesterol for trafficking to internal membranes mo...

  16. Perturbed cholesterol homeostasis in aging spinal cord.

    Science.gov (United States)

    Parkinson, Gemma M; Dayas, Christopher V; Smith, Doug W

    2016-09-01

    The spinal cord is vital for the processing of sensorimotor information and for its propagation to and from both the brain and the periphery. Spinal cord function is affected by aging, however, the mechanisms involved are not well-understood. To characterize molecular mechanisms of spinal cord aging, microarray analyses of gene expression were performed on cervical spinal cords of aging rats. Of the metabolic and signaling pathways affected, cholesterol-associated pathways were the most comprehensively altered, including significant downregulation of cholesterol synthesis-related genes and upregulation of cholesterol transport and metabolism genes. Paradoxically, a significant increase in total cholesterol content was observed-likely associated with cholesterol ester accumulation. To investigate potential mechanisms for the perturbed cholesterol homeostasis, we quantified the expression of myelin and neuroinflammation-associated genes and proteins. Although there was minimal change in myelin-related expression, there was an increase in phagocytic microglial and astrogliosis markers, particularly in the white matter. Together, these results suggest that perturbed cholesterol homeostasis, possibly as a result of increased inflammatory activation in spinal cord white matter, may contribute to impaired spinal cord function with aging. PMID:27459933

  17. Brain cholesterol in normal and pathological aging

    Directory of Open Access Journals (Sweden)

    Vanmierlo Tim

    2011-07-01

    Full Text Available Aberrations in cerebral cholesterol homeostasis can lead to severe neurological diseases. Recent findings strengthen the link between brain cholesterol metabolism and factors involved in synaptic plasticity, a process essential for learning and memory functions, as well as regeneration, which are affected in Alzheimer’s Disease (AD. Cholesterol homeostasis within the brain is independent of that in the rest of the body and needs to be strictly regulated for optimal brain functioning. In contrast with what was initially assumed brain cholesterol homeostasis can be modulated by extra-cerebral factors. We have found that enhancement of the cholesterol-turnover in the brain by administration of the synthetic activator of liver x receptos (LXRs, T0901317, leads to restoration of memory functions in an AD mouse-model.Memory in C57Bl6NCrl mice was not further improved by the same treatment. Moreover, it was found that in contrast with cholesterol, the structurally very similar dietary derived plant sterols can enter the brain. Plant sterols may be natural activators of LXRs. Evidence is provided suggesting that brassicasterol may be a novel additional biomarker in cerebrospinal fluid of AD patients. Insight into the regulation of cerebral cholesterol homeostasis will provide possibilities to modulate the key steps involved and may lead to the development of therapies for the prevention as well as treatment of neurodegenerative diseases such as AD.

  18. Cholesterol esterase activity of human intestinal mucosa

    International Nuclear Information System (INIS)

    It has been suggested that cholesterol absorption in humans is dependent on bile acid pool composition and that expansion of the cholic acid pool size is followed by an increase of the absorption values. Similar observations were reported in rats. In the present study, therefore, the authors investigated some general properties of human intestinal cholesterol esterase, with particular emphasis on the effect of bile acids on this enzymatic activity. Twenty-nine segments of small intestine were taken during operations; the enzymatic activity was studied by using mucosal homogenate as a source of enzyme and oleic acid, cholesterol, and 14C-labeled cholesterol as substrates. The time-activity relationship was linear within the first two hours; optimal pH for esterification ranged between 5 and 6.2. There was little difference between the esterifying activity of the jejunal and ileal mucosa. Esterification of cholesterol was observed with all the investigated fatty acids but was maximal with oleic acid. Bile acids did not affect cholesterol esterase activity when present in the incubation mixture at 0.1 and 1.0 mM; the enzymatic activity, however, was significantly inhibited when bile acids were added at 20 mM. In conclusion, this study has shown that the human intestinal mucosa possesses a cholesterol esterase activity; at variance with the rat, however, the human enzyme does not seem to be stimulated by trihydroxy bile acids

  19. Tissue storage and control of cholesterol metabolism in man on high cholesterol diets.

    Science.gov (United States)

    Quintão, E C; Brumer, S; Stechhahn, K

    1977-03-01

    The possibility of accumulation of tissue cholesterol in human beings submitted to high cholesterol feeding was investigated in liver biopsies and through fecal sterol balance studies. Feeding to 10 individuals 3.1 to 3.4 g/day of cholesterol for 3 weeks raised the mean serum level from 293 to 349 mg/100 ml, namely 19%, whereas the liver cholesterol content was 417 mg/100 g of wet weight. In 10 control cases eating 0.1--0.4 g/day of cholesterol serum cholesterol remained stable throughout the experimental period and the liver cholesterol content was 256 mg/100 g. Difference of liver colesterol level between the two groups was 62%. In 7 patients submitted to two periods of balance investigation on a cholesterol-free synthetic formula diet respectively prior to (PI) and after (PIII) eating the high cholesterol solid food from 4 to 15 weeks (PII), fecal steroid excretion in PIII exceeded PI in 3 patients. Such data are a direct evidence for the existence of an efficient system to release acutely stored cholesterol. In one patient bile acid excretion accounted for the difference between PIII and PI. PMID:849375

  20. Diet serum cholesterol and coronary diseases

    Directory of Open Access Journals (Sweden)

    Narindar Nath

    1961-07-01

    Full Text Available The probable sequence of events leading to atherosclerotic disease of the coronary artery and heart attack are briefly described. Blood cholesterol as a casual agent in atherosclerosis and how blood cholesterol can be modified are discussed. The effects of various dietary components particularly quality and quantity of fat and protein on the blood cholesterol concentration are discussed and it is emphasized that more work needs to be done to ascertain the role of individual components of the diet and their relative importance in atherogenesis.

  1. The role of cholesterol in membrane fusion.

    Science.gov (United States)

    Yang, Sung-Tae; Kreutzberger, Alex J B; Lee, Jinwoo; Kiessling, Volker; Tamm, Lukas K

    2016-09-01

    Cholesterol modulates the bilayer structure of biological membranes in multiple ways. It changes the fluidity, thickness, compressibility, water penetration and intrinsic curvature of lipid bilayers. In multi-component lipid mixtures, cholesterol induces phase separations, partitions selectively between different coexisting lipid phases, and causes integral membrane proteins to respond by changing conformation or redistribution in the membrane. But, which of these often overlapping properties are important for membrane fusion?-Here we review a range of recent experiments that elucidate the multiple roles that cholesterol plays in SNARE-mediated and viral envelope glycoprotein-mediated membrane fusion. PMID:27179407

  2. Triglycerides, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol in rats exposed to premium motor spirit fumes

    Directory of Open Access Journals (Sweden)

    Ogbevire L Aberare

    2011-01-01

    Full Text Available Background: Deliberate and regular exposure to premium motor spirit fumes is common and could be a risk factor for liver disease in those who are occupationally exposed. A possible association between premium motor spirit fumes and plasma levels of triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol using a rodent model could provide new insights in the pathology of diseases where cellular dysfunction is an established risk factor. Aim: The aim of this study was to evaluate the possible effect of premium motor spirit fumes on lipids and lipoproteins in workers occupationally exposed to premium motor spirit fumes using rodent model. Materials and Methods: Twenty-five Wister albino rats (of both sexes were used for this study between the 4 th of August and 7 th of September, 2010. The rats were divided into five groups of five rats each. Group 1 rats were not exposed to premium motor spirit fumes (control group, group 2 rats were exposed for 1 hour daily, group 3 for 3 hours daily, group 4 for 5 hours daily and group 5 for 7 hours daily. The experiment lasted for a period of 4 weeks. Blood samples obtained from all the groups after 4 weeks of exposure were used for the estimation of plasma levels of triglyceride, total cholesterol, high density lipoprotein- cholesterol and low density lipoprotein- cholesterol. Result: Results showed significant increase in means of plasma total cholesterol and low density lipoprotein levels (P<0.05. The mean triglyceride and total body weight were significantly lower (P<0.05 in the exposed group when compared with the unexposed. The plasma level of high density lipoprotein, the ratio of low density lipoprotein to high density lipoprotein and the ratio of total cholesterol to high density lipoprotein did not differ significantly in exposed subjects when compared with the control group. Conclusion: These results showed that frequent exposure to petrol fumes

  3. HDL: More Than Just Cholesterol

    Directory of Open Access Journals (Sweden)

    Anna Meilina

    2010-12-01

    Full Text Available BACKGROUND: Plasma concentration of high density lipoprotein cholesterol (HDL-C are strongly, consistenly, and independently inversely associated with risk of atheroschlerotic cardiovascular disease (CVD. However, the last decade has seen several observations that do not follow this simple script. CONTENT: A proteomic analysis of HDL has given us an intriguing glimpse into novel components of HDL. HDL isolated from normal humans contains several classes of proteins, including not only apolipoproteins, but also complement regulatory proteins, endopeptidase inhibitors, hemopexin, and acute phase response proteins. These observations raise the possibility of unsuspected roles for HDL. HDL delivery of complement proteins would implicate HDL in innate immunity. Serine proteinase inhibitors would enable HDL to modulate proteolysis of the vessel wall. HDL from patients with coronary artery disease was enriched in apoE, apoC-IV, apoA-IV, Paraoxonase (PON, and complement factor C3. Highlighted additional mechanisms through which HDL protects the vessel wall are: HDL improves vascular function, decreases vascular inflammation, detoxifies radicals, and limits thrombosis. SUMMARY: Both inter- and intra-organ desynchrony may be involved in the pathogenesis of cardiometabolic disease attributable to effects in brain and multiple metabolic tissues including heart, liver, fat, muscle, pancreas, and gut. Efforts to dissect the molecular mediators that coordinate circadian, metabolic, and cardiovascular systems may ultimately lead to both improved therapeutics and preventive interventions. KEYWORDS: HDL, Apo–A1, RCT, inflammation, HDL dysfunction, HDL proteome, HDL & Apo-A1 mimetics.

  4. What Do My Cholesterol Levels Mean?

    Science.gov (United States)

    ... goes beyond cholesterol levels alone and considers overall risk assessment and reduction. It's still important to know your numbers, but work with your healthcare provider to treat your risk. What numbers do ...

  5. How to Get Your Cholesterol Tested

    Science.gov (United States)

    ... six years as part of a cardiovascular risk assessment. You may need to have your cholesterol and other risk factors assessed more often if your risk is elevated. Your healthcare provider will talk with you about what your ...

  6. Cholesterol oxidation products and their biological importance.

    Science.gov (United States)

    Kulig, Waldemar; Cwiklik, Lukasz; Jurkiewicz, Piotr; Rog, Tomasz; Vattulainen, Ilpo

    2016-09-01

    The main biological cause of oxysterols is the oxidation of cholesterol. They differ from cholesterol by the presence of additional polar groups that are typically hydroxyl, keto, hydroperoxy, epoxy, or carboxyl moieties. Under typical conditions, oxysterol concentration is maintained at a very low and precisely regulated level, with an excess of cholesterol. Like cholesterol, many oxysterols are hydrophobic and hence confined to cell membranes. However, small chemical differences between the sterols can significantly affect how they interact with other membrane components, and this in turn can have a substantial effect on membrane properties. In this spirit, this review describes the biological importance and the roles of oxysterols in the human body. We focus primarily on the effect of oxysterols on lipid membranes, but we also consider other issues such as enzymatic and nonenzymatic synthesis processes of oxysterols as well as pathological conditions induced by oxysterols. PMID:26956952

  7. Structure of cholesterol/ceramide monolayer mixtures

    DEFF Research Database (Denmark)

    Scheffer, L.; Solomonov, I.; Weygand, M.J.;

    2005-01-01

    The structure of monolayers of cholesterol/ ceramide mixtures was investigated using grazing incidence x-ray diffraction, immunofluorescence, and atomic force microscopy techniques. Grazing incidence x-ray diffraction measurements showed the existence of a crystalline mixed phase of the two...... components within a range of compositions of cholesterol/ ceramide between 100: 0 and 67: 33. The mixed phase coexists with the ceramide crystalline phase in the range of compositions between 50: 50 and 30: 70; between 30: 70 and 0: 100 only the highly crystalline phase of ceramide was detected. The latter...... was determined and modeled. Immunolabeling was performed with an antibody specific to the cholesterol monohydrate crystalline arrangement. The antibody recognizes crystalline cholesterol monolayers, but does not interact with crystalline ceramide. Immunofluorescence and atomic force microscopy data...

  8. Evaluation of LDL-Cholesterol / HDL-Cholesterol Ratio as Predictor of Dyslipidemia in Subclinical Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Smita S. Kottagi

    2014-01-01

    Full Text Available Background: Subclinical hypothyroidism is defined as a serum TSH concentration above the upper limit of the reference range when serum T3 and T4 concentrations are within reference ranges. Subclinical thyroid disease is a laboratory diagnosis. Patients with subclinical disease have few or no definitive clinical signs or symptoms of thyroid dysfunction. It has been associated with higher levels of some cardiovascular risk factors. Despite some conflicting results, many studies have found that subjects with subclinical hypothyroidism have total cholesterol and low density lipoprotein cholesterol levels higher than euthyroid subjects. The association between subclinical hypothyroidism and dyslipidemia is well known. Aims and Objectives: This study is an attempt to find the importance of Low Density Lipoprotein – Cholesterol / Higher Density Lipoprotein - Cholesterol (LDL-C/HDL-C ratio rather than measurement of individual lipid profile parameters in bringing to light the dyslipidemic state associated with subclinical hypothyroidism. Materials and Methods: We studied 30 subclinical hypothyroid cases with age above 35 yrs and 30 age matched euthyroid controls. Serum T3, T4, TSH were estimated by ELISA method, serum total cholesterol, HDL Cholesterol by enzymatic CHOD-PAP method, and LDL cholesterol using Friedewald formula. Results: We found the significant increase in the serum levels of TSH (p < 0.001, Total cholesterol (p<0.001, LDL cholesterol (p<0.001, and LDL-C/HDL-C (p<0.001, Systolic blood pressure and diastolic blood pressure (p<0.001. There was no significant change in the levels of serum T3, T4, HDL- cholesterol. Conclusion: Increased levels of total cholesterol, LDL cholesterol and increased LDL-C/HDL-C ratio are seen in patients with subclinical hypothyroidism. LDL-C/HDLC ratio is a better indicator for dyslipidemia in subclinical hypothyroid cases.

  9. From blood to gut: Direct secretion of cholesterol via transintestinal cholesterol efflux

    Institute of Scientific and Technical Information of China (English)

    Carlos; LJ; Vrins

    2010-01-01

    The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol-lowering therapies. By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body. For a long time this removal via the hepatobiliary secretion was considered to be the sole route involved in the RCT. However, observations from early studies in animals and humans already pointed towards the possibility of another route. In t...

  10. A new framework for reverse cholesterol transport: Non-biliary contributions to reverse cholesterol transport

    Institute of Scientific and Technical Information of China (English)

    Ryan; E; Temel; J; Mark; Brown

    2010-01-01

    Reduction of low-density lipoprotein-cholesterol through statin therapy has only modestly decreased coronary heart disease (CHD)-associated mortality in developed countries, which has prompted the search for alternative therapeutic strategies for CHD. Major efforts are now focused on therapies that augment high-density lipoprotein (HDL)-mediated reverse cholesterol transport (RCT), and ultimately increase the fecal disposal of cholesterol. The process of RCT has long been thought to simply involve HDL-media...

  11. Dietary Phospholipids and Intestinal Cholesterol Absorption

    OpenAIRE

    Sally Tandy; Chung, Rosanna W. S.; Elaine Wat; Alvin Kamili; Cohn, Jeffrey S.

    2010-01-01

    Experiments carried out with cultured cells and in experimental animals have consistently shown that phospholipids (PLs) can inhibit intestinal cholesterol absorption. Limited evidence from clinical studies suggests that dietary PL supplementation has a similar effect in man. A number of biological mechanisms have been proposed in order to explain how PL in the gut lumen is able to affect cholesterol uptake by the gut mucosa. Further research is however required to establish whether the abili...

  12. Statin-induced chronic cholesterol depletion inhibits Leishmania donovani infection: Relevance of optimum host membrane cholesterol.

    Science.gov (United States)

    Kumar, G Aditya; Roy, Saptarshi; Jafurulla, Md; Mandal, Chitra; Chattopadhyay, Amitabha

    2016-09-01

    Leishmania are obligate intracellular protozoan parasites that invade and survive within host macrophages leading to leishmaniasis, a major cause of mortality and morbidity worldwide, particularly among economically weaker sections in tropical and subtropical regions. Visceral leishmaniasis is a potent disease caused by Leishmania donovani. The detailed mechanism of internalization of Leishmania is poorly understood. A basic step in the entry of Leishmania involves interaction of the parasite with the host plasma membrane. In this work, we have explored the effect of chronic metabolic cholesterol depletion using lovastatin on the entry and survival of Leishmania donovani in host macrophages. We show here that chronic cholesterol depletion of host macrophages results in reduction in the attachment of Leishmania promastigotes, along with a concomitant reduction in the intracellular amastigote load. These results assume further relevance since chronic cholesterol depletion is believed to mimic physiological cholesterol modulation. Interestingly, the reduction in the ability of Leishmania to enter host macrophages could be reversed upon metabolic replenishment of cholesterol. Importantly, enrichment of host membrane cholesterol resulted in reduction in the entry and survival of Leishmania in host macrophages. As a control, the binding of Escherichia coli to host macrophages remained invariant under these conditions, thereby implying specificity of cholesterol requirement for effective leishmanial infection. To the best of our knowledge, these results constitute the first comprehensive demonstration that an optimum content of host membrane cholesterol is necessary for leishmanial infection. Our results assume relevance in the context of developing novel therapeutic strategies targeting cholesterol-mediated leishmanial infection. PMID:27319380

  13. Cholesterol content in meat of some Cyprinidae

    Directory of Open Access Journals (Sweden)

    Živković Dragić L.

    2002-01-01

    Full Text Available The aim of this paper was to examine cholesterol content in meat of five Cyprinidae species: white bream (Bllica bjoerkna L, carp bream (Abramis brama L, baltic vimba (Vimba vimba carinata Pallas, zope (Abramis balerus L and crucian carp (Carassius carassius gibelio Bloch from the river Danube. Cholesterol content was examined in the function of season factor and individual weight. Cholesterol concentration in meat of white bream carp bream, baltic vimba, zope and crucian carp is on average level below 20 mg/100 g of meat, which makes meat of these fish species nutritively very valuable. Cholesterol content is variable during the season. Its concentration in meat and in lipids is lowest during spring, during summer it increases and during autumn decreases, except in meat of white bream. Body weight has influence on cholesterol content when its concentration is expressed as % of cholesterol in lipids. Its content in lipids decreases with increasing of individual weight, except in meat of carp bream.

  14. CHOLESTEROL ASSIMILATION BY COMMERCIAL YOGHURT STARTER CULTURES

    Directory of Open Access Journals (Sweden)

    Małgorzata Ziarno

    2007-03-01

    Full Text Available The ability to in vitro cholesterol level reduction in laboratory media has been shown for numerous strains of lactic acid bacteria, but not for all strains of lactic bacteria used in the dairy industry. The aim of this work was the determination of the ability of selected thermophilic lactic acid bacteria to cholesterol assimilation during 24 h culture in MRS broth. Commercial starter cultures showed various ability to cholesterol assimilation from laboratory medium. In case of starter cultures used for production of traditional yoghurt, consisting of Streptococcus salivarius subsp. thermophilus and Lactobacillus delbrueckii subsp. bulgaricus, the quantity of assimilated cholesterol did not exceed 27% of its initial contents (0.7 g in 1 dm3. Starter cultures used for bioyoghurt production, containing also probiotic strains (came from Lactobacillus acidophilus species or Bifidobacterium genus assimilated from almost 18% to over 38% of cholesterol. For one monoculture of Lb. acidophilus, cholesterol assimilation ability of 49-55% was observed, despite that the number of bacterial cells in this culture was not different from number of bacteria in other cultures.

  15. Cholesterol suppresses antimicrobial effect of statins

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Haeri

    2015-12-01

    Full Text Available Objective(s:Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in microbial metabolism is not clearly understood. It is possible that statins inhibit synthesis or utilization of some sterol precursor necessary for bacterial membrane integrity. Accordingly, this study was designed in order to examine if statins inhibit the production of a compound, which can be used in the membrane, and whether cholesterol would replace it and rescue bacteria from toxic effects of statins. Materials and Methods: To examine the possibility we assessed antibacterial effect of statins with different classes; lovastatin, simvastatin, and atorvastatin, alone and in combination with cholesterol on two Gram-positive (Staphylococcus aureus and Enterococcus faecalis and two Gram-negative (Pseudomonas aeruginosa and Escherichia coli bacteria using gel diffusion assay. Results: Our results showed that all of the statins except for lovastatin had significant antibacterial property in S. aureus, E. coli, and Enter. faecalis. Surprisingly, cholesterol nullified the antimicrobial action of effective statins in statin-sensitive bacteria. Conclusion: It is concluded that statins may deprive bacteria from a metabolite responsible for membrane stability, which is effectively substituted by cholesterol.

  16. Dietary cholesterol modulates pathogen blocking by Wolbachia.

    Directory of Open Access Journals (Sweden)

    Eric P Caragata

    Full Text Available The bacterial endosymbiont Wolbachia pipientis protects its hosts from a range of pathogens by limiting their ability to form infections inside the insect. This "pathogen blocking" could be explained by innate immune priming by the symbiont, competition for host-derived resources between pathogens and Wolbachia, or the direct modification of the cell or cellular environment by Wolbachia. Recent comparative work in Drosophila and the mosquito Aedes aegypti has shown that an immune response is not required for pathogen blocking, implying that there must be an additional component to the mechanism. Here we have examined the involvement of cholesterol in pathogen blocking using a system of dietary manipulation in Drosophila melanogaster in combination with challenge by Drosophila C virus (DCV, a common fly pathogen. We observed that flies reared on cholesterol-enriched diets infected with the Wolbachia strains wMelPop and wMelCS exhibited reduced pathogen blocking, with viral-induced mortality occurring 2-5 days earlier than flies reared on Standard diet. This shift toward greater virulence in the presence of cholesterol also corresponded to higher viral copy numbers in the host. Interestingly, an increase in dietary cholesterol did not have an effect on Wolbachia density except in one case, but this did not directly affect the strength of pathogen blocking. Our results indicate that host cholesterol levels are involved with the ability of Wolbachia-infected flies to resist DCV infections, suggesting that cholesterol contributes to the underlying mechanism of pathogen blocking.

  17. Dairy products and plasma cholesterol levels

    Directory of Open Access Journals (Sweden)

    Lena Ohlsson

    2010-08-01

    Full Text Available Cholesterol synthesized in the body or ingested is an essential lipid component for human survival from our earliest life. Newborns ingest about 3–4 times the amount per body weight through mother's milk compared to the dietary intake of adults. A birth level of 1.7 mmol/L plasma total cholesterol will increase to 4–4.5 mmol/L during the nursing period and continue to increase from adulthood around 40% throughout life. Coronary artery disease and other metabolic disorders are strongly associated with low-density lipoprotein (LDL and high-density lipoprotein (HDL cholesterol as well as triacylglycerol concentration. Milk fat contains a broad range of fatty acids and some have a negative impact on the cholesterol rich lipoproteins. The saturated fatty acids (SFAs, such as palmitic acid (C16:0, myristic acid (C14:0, and lauric acid (C12:0, increase total plasma cholesterol, especially LDL, and constitute 11.3 g/L of bovine milk, which is 44.8% of total fatty acid in milk fat. Replacement of dairy SFA and trans-fatty acids with polyunsaturated fatty acids decreases plasma cholesterol, especially LDL cholesterol, and is associated with a reduced risk of cardiovascular disease. Available data shows different effects on lipoproteins for different dairy products and there is uncertainty as to the impact a reasonable intake amount of dairy items has on cardiovascular risk. The aim of this review is to elucidate the effect of milk components and dairy products on total cholesterol, LDL, HDL, and the LDL/HDL quotients. Based on eight recent randomized controlled trials of parallel or cross-over design and recent reviews it can be concluded that replacement of saturated fat mainly (but not exclusively derived from high-fat dairy products with low-fat dairy products lowers LDL/HDL cholesterol and total/HDL cholesterol ratios. Whey, dairy fractions enriched in polar lipids, and techniques such as fermentation, or fortification of cows feeding can be used

  18. Chromatographic separation of cholesterol in foods.

    Science.gov (United States)

    Fenton, M

    1992-10-30

    Based on the current literature and on experience gained in the laboratory, a simplified procedure using direct saponification (0.4 M potassium hydroxide in ethanol and heating at 60 degrees C for 1 h) is the most appropriate method for the determination of total cholesterol in foods. Extraction of the unsaponifiable matter with hexane is efficient and no extra clean-up is required before quantification. An internal standard, 5 alpha-cholestane or epicoprostanol, should be added to the sample prior to saponification and, together with reference standards, carried through the entire procedure to ensure accurate results. A significant improvement in cholesterol methodology has been achieved by decreasing the sample size and performing all the sample preparation steps in a single tube. The method has the advantages of elimination of an initial solvent extraction for total lipids and errors resulting from multiple extractions, transfers, filtration and wash steps after saponification. The resulting hexane extract, which contains a variety of sterols and fat soluble vitamins, requires an efficient capillary column for complete resolution of cholesterol from the other compounds present. The development of fused-silica capillary columns using cross-linked and bonded liquid phases has provided high thermal stability, inertness and separation efficiency and, together with automated cold on-column gas chromatographic injection systems, has resulted in reproducible cholesterol determinations in either underivatized or derivatized form. If free cholesterol and its esters need to be determined separately, they are initially extracted with other lipids with chloroform-methanol followed by their separation by column or thin-layer chromatography and subsequently analysed by gas or liquid chromatography. Although capillary gas chromatography offers superior efficiency in separation, the inherent benefits of liquid chromatography makes it a potential alternative. Isotope dilution

  19. Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

    Science.gov (United States)

    Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

    2016-03-01

    This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. PMID:26710098

  20. Cholesterol efflux analyses using stable isotopes and mass spectrometry

    OpenAIRE

    Robert J Brown; Shao, Fei; Baldán, Ángel; Albert, Carolyn J.; Ford, David A.

    2012-01-01

    Cholesterol efflux from macrophages and the vascular wall is the initial step of the cardiovascular protective reverse cholesterol transport process. This study demonstrates a mass spectrometry based assay to measure the cellular and media content of [d7]-cholesterol and unlabeled cholesterol that can be used to measure cholesterol efflux from cell lines. Using a triple quadrupole ESI-MS instrument in direct infusion mode, product ion scanning for m/z 83, neutral loss (NL) 375.5 scanning and ...

  1. Cholesterol and ocular pathologies: focus on the role of cholesterol-24S-hydroxylase in cholesterol homeostasis

    Directory of Open Access Journals (Sweden)

    Fourgeux Cynthia

    2015-03-01

    Full Text Available The retina is responsible for coding the light stimulus into a nervous signal that is transferred to the brain via the optic nerve. The retina is formed by the association of the neurosensory retina and the retinal pigment epithelium that is supported by Bruch’s membrane. Both the physical and metabolic associations between these partners are crucial for the functioning of the retina, by means of nutrient intake and removal of the cell and metabolic debris from the retina. Dysequilibrium are involved in the aging processes and pathologies such as age-related macular degeneration, the leading cause of visual loss after the age of 50 years in Western countries. The retina is composed of several populations of cells including glia that is involved in cholesterol biosynthesis. Cholesterol is the main sterol in the retina. It is present as free form in cells and as esters in Bruch’s membrane. Accumulation of cholesteryl esters has been associated with aging of the retina and impairment of the retinal function. Under dietary influence and in situ synthesized, the metabolism of cholesterol is regulated by cell interactions, including neurons and glia via cholesterol-24S-hydroxylase. Several pathophysiological associations with cholesterol and its metabolism can be suggested, especially in relation to glaucoma and age-related macular degeneration.

  2. Emerging roles of the intestine in control of cholesterol metabolism

    Institute of Scientific and Technical Information of China (English)

    Janine K Kruit; Albert K Groen; Theo J van Berkel; Folkert Kuipers

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis,clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor to high density lipoprotein (HDL; good cholesterol) formation. The liver has a central position in the classical definition of the reverse cholesterol transport pathway by taking up peripheryderived cholesterol from lipoprotein particles followed by conversion into bile acids or its direct secretion into bile for eventual removal via the feces. During the past couple of years, however, an additional important role of the intestine in maintenance of cholesterol homeostasis and regulation of plasma cholesterol levels has become apparent. Firstly, molecular mechanisms of cholesterol absorption have been elucidated and novel pharmacological compounds have been identified that interfere with the process and positively impact plasma cholesterol levels. Secondly, it is now evident that the intestine itself contributes to fecal neutral sterol loss as a cholesterol-secreting organ. Finally, very recent work has unequivocally demonstrated that the intestine contributes significantly to plasma HDL cholesterol levels.Thus, the intestine is a potential target for novel antiatherosclerotic treatment strategies that, in addition to interference with cholesterol absorption, modulate direct cholesterol excretion and plasma HDL cholesterol levels.

  3. A novel alkyne cholesterol to trace cellular cholesterol metabolism and localization.

    Science.gov (United States)

    Hofmann, Kristina; Thiele, Christoph; Schött, Hans-Frieder; Gaebler, Anne; Schoene, Mario; Kiver, Yuriy; Friedrichs, Silvia; Lütjohann, Dieter; Kuerschner, Lars

    2014-03-01

    Cholesterol is an important lipid of mammalian cells and plays a fundamental role in many biological processes. Its concentration in the various cellular membranes differs and is tightly regulated. Here, we present a novel alkyne cholesterol analog suitable for tracing both cholesterol metabolism and localization. This probe can be detected by click chemistry employing various reporter azides. Alkyne cholesterol is accepted by cellular enzymes from different biological species (Brevibacterium, yeast, rat, human) and these enzymes include cholesterol oxidases, hydroxylases, and acyl transferases that generate the expected metabolites in in vitro and in vivo assays. Using fluorescence microscopy, we studied the distribution of cholesterol at subcellular resolution, detecting the lipid in the Golgi and at the plasma membrane, but also in the endoplasmic reticulum and mitochondria. In summary, alkyne cholesterol represents a versatile, sensitive, and easy-to-use tool for tracking cellular cholesterol metabolism and localization as it allows for manifold detection methods including mass spectrometry, thin-layer chromatography/fluorography, and fluorescence microscopy. PMID:24334219

  4. Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis

    OpenAIRE

    Sonawane Nitin D; Previs Stephen F; Jiang Dechen; Ruddy Jennifer; Manson Mary E; West Richard H; Fang Danjun; Burgess James D; Kelley Thomas J

    2010-01-01

    Abstract Background Previous observations demonstrate that Cftr-null cells and tissues exhibit alterations in cholesterol processing including perinuclear cholesterol accumulation, increased de novo synthesis, and an increase in plasma membrane cholesterol accessibility compared to wild type controls. The hypothesis of this study is that membrane cholesterol accessibility correlates with CFTR genotype and is in part influenced by de novo cholesterol synthesis. Methods Electrochemical detectio...

  5. Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

    DEFF Research Database (Denmark)

    Varbo, Anette; Tybjærg-Hansen, Anne; Nordestgaard, Børge G;

    2013-01-01

    Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown....

  6. Lipoproteins, cholesterol homeostasis and cardiac health

    Directory of Open Access Journals (Sweden)

    Tyler F. Daniels, Karen M. Killinger, Jennifer J. Michal, Raymond W. Wright Jr., Zhihua Jiang

    2009-01-01

    Full Text Available Cholesterol is an essential substance involved in many functions, such as maintaining cell membranes, manufacturing vitamin D on surface of the skin, producing hormones, and possibly helping cell connections in the brain. When cholesterol levels rise in the blood, they can, however, have dangerous consequences. In particular, cholesterol has generated considerable notoriety for its causative role in atherosclerosis, the leading cause of death in developed countries around the world. Homeostasis of cholesterol is centered on the metabolism of lipoproteins, which mediate transport of the lipid to and from tissues. As a synopsis of the major events and proteins that manage lipoprotein homeostasis, this review contributes to the substantial attention that has recently been directed to this area. Despite intense scrutiny, the majority of phenotypic variation in total cholesterol and related traits eludes explanation by current genetic knowledge. This is somewhat disappointing considering heritability estimates have established these traits as highly genetic. Thus, the continued search for candidate genes, mutations, and mechanisms is vital to our understanding of heart disease at the molecular level. Furthermore, as marker development continues to predict risk of vascular illness, this knowledge has the potential to revolutionize treatment of this leading human disease.

  7. Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

    Science.gov (United States)

    Alsop, Richard; Barrett, Matthew; Zheng, Sonbo; Dies, Hannah; Rheinstadter, Maikel

    2014-03-01

    Aspirin (ASA) is often prescribed for patients with high levels of cholesterol for the secondary prevention of myocardial events, a regimen known as the Low-Dose Aspirin Therapy. We have recently shown that Aspirin partitions in lipid bilayers. However, a direct interplay between ASA and cholesterol has not been investigated. Cholesterol is known to insert itself into the membrane in a dispersed state at moderate concentrations (under ~37.5%) and decrease fluidity of membranes. We prepared model lipid membranes containing varying amounts of both ASA and cholesterol molecules. The structure of the bilayers as a function of ASA and cholesterol concentration was determined using high-resolution X-ray diffraction. At cholesterol levels of more than 40mol%, immiscible cholesterol plaques formed. Adding ASA to the membranes was found to dissolve the cholesterol plaques, leading to a fluid lipid bilayer structure. We present first direct evidence for an interaction between ASA and cholesterol on the level of the cell membrane.

  8. Ordering effects of cholesterol and its analogues

    DEFF Research Database (Denmark)

    Róg, Tomasz; Pasenkiewicz-Gierula, Marta; Vattulainen, Ilpo;

    2009-01-01

    Without any exaggeration, cholesterol is one of the most important lipid species in eukaryotic cells. Its effects on cellular membranes and functions range from purely mechanistic to complex metabolic ones, besides which it is also a precursor of the sex hormones (steroids) and several vitamins. In...... this review, we discuss the biophysical effects of cholesterol on the lipid bilayer, in particular the ordering and condensing effects, concentrating on the molecular level or inter-atomic interactions perspective, starting from two-component systems and proceeding to many-component ones e.g., modeling...... lipid rafts. Particular attention is paid to the roles of the methyl groups in the cholesterol ring system, and their possible biological function. Although our main research methodology is computer modeling, in this review we make extensive comparisons between experiments and different modeling...

  9. CHOBIMALT: A Cholesterol-Based Detergent†

    Science.gov (United States)

    Howell, Stanley C.; Mittal, Ritesh; Huang, Lijun; Travis, Benjamin; Breyer, Richard M.; Sanders, Charles R.

    2010-01-01

    Cholesterol and its hemisuccinate and sulfate derivatives are widely used in studies of purified membrane proteins, but are difficult to solubilize in aqueous solution, even in the presence of detergent micelles. Other cholesterol derivatives do not form conventional micelles and lead to viscous solutions. To address these problems a cholesterol-based detergent, CHOBIMALT, has been synthesized and characterized. At concentrations above 3–4μM, CHOBIMALT forms micelles without the need for elevated temperatures or sonic disruption. Diffusion and fluorescence measurements indicated that CHOBIMALT micelles are large (210 ± 30 kDa). The ability to solubilize a functional membrane protein was explored using a G-protein coupled receptor, the human kappa opioid receptor type 1 (hKOR1). While CHOBIMALT alone was not found to be effective as a surfactant for membrane extraction, when added to classical detergent micelles CHOBIMALT was observed to dramatically enhance the thermal stability of solubilized hKOR1. PMID:20919740

  10. Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis

    Directory of Open Access Journals (Sweden)

    Sonawane Nitin D

    2010-05-01

    Full Text Available Abstract Background Previous observations demonstrate that Cftr-null cells and tissues exhibit alterations in cholesterol processing including perinuclear cholesterol accumulation, increased de novo synthesis, and an increase in plasma membrane cholesterol accessibility compared to wild type controls. The hypothesis of this study is that membrane cholesterol accessibility correlates with CFTR genotype and is in part influenced by de novo cholesterol synthesis. Methods Electrochemical detection of cholesterol at the plasma membrane is achieved with capillary microelectrodes with a modified platinum coil that accepts covalent attachment of cholesterol oxidase. Modified electrodes absent cholesterol oxidase serves as a baseline control. Cholesterol synthesis is determined by deuterium incorporation into lipids over time. Incorporation into cholesterol specifically is determined by mass spectrometry analysis. All mice used in the study are on a C57Bl/6 background and are between 6 and 8 weeks of age. Results Membrane cholesterol measurements are elevated in both R117H and ΔF508 mouse nasal epithelium compared to age-matched sibling wt controls demonstrating a genotype correlation to membrane cholesterol detection. Expression of wt CFTR in CF epithelial cells reverts membrane cholesterol to WT levels further demonstrating the impact of CFTR on these processes. In wt epithelial cell, the addition of the CFTR inhibitors, Gly H101 or CFTRinh-172, for 24 h surprisingly results in an initial drop in membrane cholesterol measurement followed by a rebound at 72 h suggesting a feedback mechanism may be driving the increase in membrane cholesterol. De novo cholesterol synthesis contributes to membrane cholesterol accessibility. Conclusions The data in this study suggest that CFTR influences cholesterol trafficking to the plasma membrane, which when depleted, leads to an increase in de novo cholesterol synthesis to restore membrane content.

  11. The cholesterol system of the swine

    International Nuclear Information System (INIS)

    The purpose of this work was to characterize the dynamic system of adult female Large White swine. The content of this system and its relationships with both the external environment and between the different parts of the system were explained. The analysis of these results in terms of compared physiology showed that the structure of the cholesterol system was the same in man and in the swine. Consequently, the swine constitutes a good biological tool to study human cholesterol indirectly and to foresee the changes that might be induced in various physio-pathological cases. (author)

  12. Electron Transfer Pathways in Cholesterol Synthesis.

    Science.gov (United States)

    Porter, Todd D

    2015-10-01

    Cholesterol synthesis in the endoplasmic reticulum requires electron input at multiple steps and utilizes both NADH and NADPH as the electron source. Four enzymes catalyzing five steps in the pathway require electron input: squalene monooxygenase, lanosterol demethylase, sterol 4α-methyl oxidase, and sterol C5-desaturase. The electron-donor proteins for these enzymes include cytochrome P450 reductase and the cytochrome b5 pathway. Here I review the evidence for electron donor protein requirements with these enzymes, the evidence for additional electron donor pathways, and the effect of deletion of these redox enzymes on cholesterol and lipid metabolism. PMID:26344922

  13. Analysis of Cholesterol Trafficking with Fluorescent Probes

    DEFF Research Database (Denmark)

    Maxfield, Frederick R.; Wustner, Daniel

    2012-01-01

    processes are not well understood. Fluorescence microscopy is a valuable tool for studying intracellular transport processes, but this method can be challenging for lipid molecules because addition of a fluorophore may alter the properties of the molecule greatly. We discuss the use of fluorescent molecules...... that can bind to cholesterol to reveal its distribution in cells. We also discuss the use of intrinsically fluorescent sterols that closely mimic cholesterol, as well as some minimally modified fluorophore-labeled sterols. Methods for imaging these sterols by conventional fluorescence microscopy and by...

  14. From blood to gut: Direct secretion of cholesterol via transintestinal cholesterol efflux

    Directory of Open Access Journals (Sweden)

    Carlos LJ Vrins

    2010-12-01

    Full Text Available The reverse cholesterol transport pathway (RCT is the focus of many cholesterol-lowering therapies. By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body. For a long time this removal via the hepatobiliary secretion was considered to be the sole route involved in the RCT. However, observations from early studies in animals and humans already pointed towards the possibility of another route. In the last few years it has become evident that a non-biliary cholesterol secretion pathway exists in which the intestine plays a central role. This transintestinal cholesterol efflux (TICE pathway contributes significantly to the total fecal neutral sterol excretion. Moreover, recent studies have shown that TICE is also sensitive to stimulation. As a consequence, the direct role of cholesterol secretion from blood via TICE makes the intestine a suitable and approachable target for cholesterol removal from the body and possibly reduction of atherosclerosis. In this review, the discovery and recent findings contributing to understanding the mechanism of TICE will be discussed.

  15. Effect of Processing Methods on Cholesterol Contents and Cholesterol Oxides Formation in Some Dairy Products

    International Nuclear Information System (INIS)

    The effects of pasteurization, boiling, microwaving, processing and storage of milk and some locally produced dairy products on cholesterol contents and cholesterol oxides formation were studied and evaluated. The 7-ketocholesterol were not detected (ND) in all raw milk samples. On the contrary, heating of milk led to formation of cholesterol oxidation products (COPs), mostly, 7- ketocholesterol in different quantities. No significant effect of heating of milk on cholesterol level was observed with the exception of the ultra-high temperature (UHT) milk prepared from milk powder heated at 140 + - 1.0 degree C for 4 sec showed the highest value of 7-ketocholesterol (80.97 mgg-1), followed by microwave heated milk for 5 min (31.29 mgg-1), whereas the lowest value was in milk pasteurized at 85 + - 1.0 degree C for 16 sec (3.125 mgg-1). Commercial storage showed no significant effect on cholesterol and 7-ketocholestrol but lowered cholesterol concentration and increased 7-ketocholestrol level of UHT reconstituted milk. Cholesterol content of both yogurt and labaneh strained by centrifugal separator showed significant decrease while 7-ketochostrol level was increased significantly with refrigerated storage. The findings are discussed in the context with the results of previous similar studies. (author)

  16. Cholesterol homeostasis: How do cells sense sterol excess?

    Science.gov (United States)

    Howe, Vicky; Sharpe, Laura J; Alexopoulos, Stephanie J; Kunze, Sarah V; Chua, Ngee Kiat; Li, Dianfan; Brown, Andrew J

    2016-09-01

    Cholesterol is vital in mammals, but toxic in excess. Consequently, elaborate molecular mechanisms have evolved to maintain this sterol within narrow limits. How cells sense excess cholesterol is an intriguing area of research. Cells sense cholesterol, and other related sterols such as oxysterols or cholesterol synthesis intermediates, and respond to changing levels through several elegant mechanisms of feedback regulation. Cholesterol sensing involves both direct binding of sterols to the homeostatic machinery located in the endoplasmic reticulum (ER), and indirect effects elicited by sterol-dependent alteration of the physical properties of membranes. Here, we examine the mechanisms employed by cells to maintain cholesterol homeostasis. PMID:26993747

  17. Cholesterol versus cholesterol sulfate: effects on properties of phospholipid bilayers containing docosahexaenoic acid.

    Science.gov (United States)

    Schofield, M; Jenski, L J; Dumaual, A C; Stillwell, W

    1998-09-01

    The important omega-3 fatty acid docosahexaenoic acid (DHA) is present at high concentration in some membranes that also contain the unusual sterol cholesterol sulfate (CS). The association between these lipids and their effect on membrane structure is presented here. Differential scanning calorimetry (DSC), MC540 fluorescence, erythritol permeability, pressure/area isotherms on lipid monolayers and molecular modeling are used to compare the effect of CS and cholesterol on model phospholipid membranes. By DSC, CS decreases the main phase transition temperature and broadens the transitions of dipalmitolyphosphatidylcholine (DPPC), 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (18:0,18:1 PC) and 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (18:0,22:6 PC) to a much larger extent than does cholesterol. In addition CS produces a three-component transition in 18:0,18:1 PC bilayers that is not seen with cholesterol. In a mixed phospholipid bilayer composed of 18:0,18:1 PC/18:0,22:6 PC (1:1, mol/mol), CS at 2.5 membrane mol% or more induces lateral phase separation while cholesterol does not. CS decreases lipid packing density and increases permeability of 18:0,18:1 PC and 18:0,22:6 PC bilayers to a much larger extent than cholesterol. CS disrupts oleic acid-containing bilayers more than those containing DHA. Molecular modeling confirms that the anionic sulfate moiety on CS renders this sterol more polar than cholesterol with the consequence that CS likely resides higher (extends further into the aqueous environment) in the bilayer. CS can therefore be preferentially accommodated into DHA-enriched bilayers where its tetracyclic ring system may fit into the delta 4 pocket of DHA, a location excluded to cholesterol. It is proposed that CS may in part replace the membrane function of cholesterol in DHA-rich membranes. PMID:9807808

  18. Potential of BODIPY-cholesterol for analysis of cholesterol transport and diffusion in living cells

    DEFF Research Database (Denmark)

    Wüstner, Daniel; Lund, Frederik Wendelboe; Röhrl, Clemens; Stangl, Herbert

    2016-01-01

    Cholesterol is an abundant and important lipid component of cellular membranes. Analysis of cholesterol transport and diffusion in living cells is hampered by the technical challenge of designing suitable cholesterol probes which can be detected for example by optical microscopy. One strategy is to...... collaborative efforts with Bob Bittman for studying diffusion in the plasma membrane (PM) and uptake of BChol in a quantitative manner. For that purpose, we used a variety of fluorescence approaches including fluorescence correlation spectroscopy and its imaging variants, fluorescence recovery after...

  19. Biliary cholesterol secretion: More than a simple ABC

    Directory of Open Access Journals (Sweden)

    Arne Dikkers, Uwe JF Tietge

    2010-12-01

    Full Text Available Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the final step for the elimination of cholesterol originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the main pathophysiological determinant of cholesterol gallstone formation. This review summarizes current knowledge on the origins of cholesterol secreted into the bile as well as the relevant processes and transporters involved. Next to the established ATP-binding cassette (ABC transporters mediating the biliary secretion of bile acids (ABCB11, phospholipids (ABCB4 and cholesterol (ABCG5/G8, special attention is given to emerging proteins that modulate or mediate biliary cholesterol secretion. In this regard, the potential impact of the phosphatidylserine flippase ATPase class I type 8B member 1, the Niemann Pick C1-like protein 1 that mediates cholesterol absorption and the high density lipoprotein cholesterol uptake receptor, scavenger receptor class B type I, is discussed.

  20. Effects of apolipoproteins on the kinetics of cholesterol exchange

    Energy Technology Data Exchange (ETDEWEB)

    Letizia, J.Y.; Phillips, M.C. (Medical College of Pennsylvania, Philadelphia (USA))

    1991-01-22

    The effects of apolipoproteins on the kinetics of cholesterol exchange have been investigated by monitoring the transfer of ({sup 14}C)cholesterol from donor phospholipid/cholesterol complexes containing human apolipoproteins A, B, or C. Negatively charged discoidal and vesicular particles containing purified apolipoproteins complexed with lipid and a trace of ({sup 14}C)cholesterol were incubated with a 10-fold excess of neutral, acceptor, small unilamellar vesicles. The donor and acceptor particles were separated by chromatogrphy of DEAE-Sepharose, and the rate of movement of labeled cholesterol was analyzed as a first-order exchange process. The kinetics of exchange of cholesterol from both vesicular and discoidal complexes that contain apoproteins are consistent with an aqueous diffusion mechanism, as has been established previously for PC/cholesterol SUV. Apolipoproteins A-I, A-II, reduced and carboxymethylated A-11, and B-100 present in SUV at the same lipid/protein (w/w) ratio all enhance the rate of cholesterol exchange to about the same degree. Cholesterol molecules exchange more rapidly from discoidal complexes. Generally, as the diameter of apoprotein/phospholipid/cholesterol discs decreases, t{sub 1/2} for cholesterol exchange decreases. Since small bilayer discs have a relatively high ratio of boundary to face surface area, cholesterol molecules desorb more rapidly than from larger discs. The modulation of lipid packing by the apoprotein molecules present at the surface of lipoprotein particles affects the rate of cholesterol exchange from such particles.

  1. The Success Story of LDL Cholesterol Lowering.

    Science.gov (United States)

    Pedersen, Terje R

    2016-02-19

    We can look back at >100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein-cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence. PMID:26892969

  2. [Giant cholesterol cysts of the petrous apex].

    Science.gov (United States)

    Pellet, W; Valenzuela, S; Malca, S; Cannoni, M; Perez-Castillo, A M

    1992-01-01

    In connection with their two own cases, the authors deal about the giant cholesterol cysts of the petrous apex. The lesions which are to be differentiated from epidermoid cysts are cholesterol granulomas. Their petrous apex location explains their characteristic large appearance. As each cholesterol granuloma, they occur when a bony cell is obstructed. This chronic obstruction induces mucosal edema then bleedings which lead to the formation and, by the lack of drainage, to the accumulation of cholesterol crystals. These crystals initiate a non specific reaction to foreign bodies, a granuloma, which also can bleed. Thus, a continuous cycle perpetuates the growth of the lesion. This lesion, when it is localized in the petrous apex, can reach a big size before the appearance of some signs. Usually, these are otologic (sensorineural hearing loss, tinnitus, vertigo) and/or cranial nerve palsies (V, VI, VII). C.T. scan (well defined, sharply marginated bony expansible lesion with isodense to the brain central part) and M.R.I. (central region of increased intensity on both T1 and T2 weighted images and peripheral rim of markedly decreased signal intensity in all instances) features are characteristic enough to allow diagnose with other petrous apex lesions (cholesteatoma, mucocele, epithelial cyst, histiocytosis X, ...). Surgical treatment must try to evacuate and to aerate the cavity or perhaps to obliterate it with fatty pieces in order to prevent the recurrence. PMID:1299772

  3. Mitochondria, cholesterol and cancer cell metabolism.

    Science.gov (United States)

    Ribas, Vicent; García-Ruiz, Carmen; Fernández-Checa, José C

    2016-12-01

    Given the role of mitochondria in oxygen consumption, metabolism and cell death regulation, alterations in mitochondrial function or dysregulation of cell death pathways contribute to the genesis and progression of cancer. Cancer cells exhibit an array of metabolic transformations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which ensure cancer progression. Cholesterol metabolism is disturbed in cancer cells and supports uncontrolled cell growth. In particular, the accumulation of cholesterol in mitochondria emerges as a molecular component that orchestrates some of these metabolic alterations in cancer cells by impairing mitochondrial function. As a consequence, mitochondrial cholesterol loading in cancer cells may contribute, in part, to the Warburg effect stimulating aerobic glycolysis to meet the energetic demand of proliferating cells, while protecting cancer cells against mitochondrial apoptosis due to changes in mitochondrial membrane dynamics. Further understanding the complexity in the metabolic alterations of cancer cells, mediated largely through alterations in mitochondrial function, may pave the way to identify more efficient strategies for cancer treatment involving the use of small molecules targeting mitochondria, cholesterol homeostasis/trafficking and specific metabolic pathways. PMID:27455839

  4. Practical radiochromatographic assay for cholesterol epoxide hydrase

    International Nuclear Information System (INIS)

    A method for the assay of cholesterol epoxide hydrase activity is described. The assay involves the thin-layer chromatographic separation and quantitation of radiolabeled cholestan-3β,5α,6α-epoxide and its major hydration product, cholestan-3β,5α,6β-triol. Radiochromatographic scanning is employed to quantitate the reaction. The procedure is sensitive, rapid, and nondestructive

  5. Weight Loss Surgery May Boost Good Cholesterol in Obese Boys

    Science.gov (United States)

    ... or federal policy. More Health News on: Cholesterol Obesity in Children Weight Loss Surgery Recent Health News Related MedlinePlus Health Topics Cholesterol Obesity in Children Weight Loss Surgery About MedlinePlus Site Map FAQs ...

  6. Cholesterol-induced protein sorting: an analysis of energetic feasibility

    DEFF Research Database (Denmark)

    Lundbaek, J A; Andersen, O S; Werge, T;

    2003-01-01

    thickness. In this model, Golgi proteins with short TMDs would be excluded from cholesterol-enriched domains (lipid rafts) that are incorporated into transport vesicles destined for the plasma membrane. Although attractive, this model remains unproven. We therefore evaluated the energetic feasibility of a...... cholesterol-dependent sorting process using the theory of elastic liquid crystal deformations. We show that the distribution of proteins between cholesterol-enriched and cholesterol-poor bilayer domains can be regulated by cholesterol-induced changes in the bilayer physical properties. Changes in bilayer...... thickness per se, however, have only a modest effect on sorting; the major effect arises because cholesterol changes also the bilayer material properties, which augments the energetic penalty for incorporating short TMDs into cholesterol-enriched domains. We conclude that cholesterol-induced changes in the...

  7. Plasma Ubiquinone, Alpha-Tocopherol and Cholesterol in Man

    DEFF Research Database (Denmark)

    Karlsson, Jan; Diamant, Bertil; Edlund, Per Olof;

    1992-01-01

    Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle......Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle...

  8. Trans Fat Now Listed With Saturated Fat and Cholesterol

    Science.gov (United States)

    ... Trans Fat Now Listed With Saturated Fat and Cholesterol Share Tweet Linkedin Pin it More sharing options ... I Do About Saturated Fat, Trans Fat, and Cholesterol? When comparing foods, look at the Nutrition Facts ...

  9. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne;

    2011-01-01

    Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population....

  10. Talk with Your Health Care Provider about High Cholesterol

    Science.gov (United States)

    ... you do? Always ask your provider what your cholesterol numbers are and write them down. Discuss these ... provider may prescribe medicine to help lower your cholesterol. y y Take your medicine every day, or ...

  11. Hearing Outcomes after Surgical Drainage of Petrous Apex Cholesterol Granuloma

    OpenAIRE

    Rihani, Jordan; Kutz, J. Walter; Isaacson, Brandon

    2014-01-01

    Objective This study aims to assess the hearing outcomes of patients undergoing surgical management of petrous apex cholesterol granuloma and to discuss the role of otic capsule–sparing approaches in drainage of petrous apex cholesterol granulomas.

  12. Enzymatic Quantification of Cholesterol and Cholesterol Esters from Silicone Hydrogel Contact Lenses

    OpenAIRE

    Pucker, Andrew D.; Thangavelu, Mirunalni; Nichols, Jason J.

    2010-01-01

    There is significant interest in lipid deposition associated with current silicone hydrogel contact lens materials. This work describes the application of a cholesterol assay used to examine this question.

  13. Fluorimetric determination of cholesterol in hypercholesterolemia serum

    Science.gov (United States)

    Lan, Xiufeng; Liu, Jiangang; Liu, Ying; Luo, Xiaosen; Lu, Jian; Ni, Xiaowu

    2005-01-01

    With the increase of people"s living standard and the changes of living form, the number of people who suffer from hypercholesterolemia is increasing. It is not only harmful to heart and blood vessel, but also leading to obstruction of cognition. The conventional blood detection technology has weakness such as complex operation, long detecting period, and bad visibility. In order to develop a new detection method that can checkout hypercholesterolemia conveniently, spectroscopy of cholesterol in hypercholesterolemia serum is obtained by the multifunctional grating spectrograph. The experiment results indicate that, under the excitation of light-emitting diode (LED) with the wavelength at 407 nm, the serum from normal human and the hypercholesterolemia serum emit different fluorescence spectra. The former can emit one fluorescence region with the peak locating at 516 nm while the latter can emit two more regions with peaks locating at 560 nm and 588 nm. Moreover, the fluorescence intensity of serum is non-linear increasing with the concentration of cholesterol increases when the concentration of cholesterol is lower than 13.8 mmol/L, and then, with the concentration of cholesterol increase, the fluorescence intensity decreases. However, the fluorescence intensity is still much higher than that of serum from normal human. Conclusions can be educed from the experiments: the intensity and the shape of fluorescence spectra of hypercholesterolemia serum are different of those of normal serum, from which the cholesterol abnormal in blood can be judged. The consequences in this paper may offer an experimental reference for the diagnosis of the hypercholesterolemia.

  14. Effect of dietary cholesterol on plasma cholesterol concentration in subjects following reduced fat, high fibre diet.

    OpenAIRE

    Edington, J.; Geekie, M; Carter, R.; Benfield, L; Fisher, K; Ball, M.; J. Mann

    1987-01-01

    One hundred and sixty eight subjects participated in a randomised crossover study to determine whether halving or doubling the present dietary cholesterol intake from eggs had any influence on blood cholesterol concentration in people following current dietary recommendations. During the first eight weeks all participants were advised to follow a reduced fat diet (26% total energy for hyperlipidaemic patients, 35% total energy for normolipidaemic volunteers) with an increased ratio of polyuns...

  15. Electron Microscopic Localization of Cholesterol in Bovine Milk Fat Globules

    OpenAIRE

    Martin, Robert W.

    1989-01-01

    An electron microscopic method designed for the detection of cholesterol in milk fat was evaluated for reliability. This method is based on the incubation of cream from raw milk with fillipin (a polyene antibiotic) which has a specific affinity for cholesterol followed by freeze fracturing and electron microscopic examination of fat globules. Cholesterol was localized within the membrane and the triglyceride core of milk fat globules. Cholesterol was highly organized within membrane portio...

  16. Remnant cholesterol as a cause of ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Nordestgaard, Børge G

    2014-01-01

    This review focuses on remnant cholesterol as a causal risk factor for ischemic heart disease (IHD), on its definition, measurement, atherogenicity, and levels in high risk patient groups; in addition, present and future pharmacological approaches to lowering remnant cholesterol levels...... are considered. Observational studies show association between elevated levels of remnant cholesterol and increased risk of cardiovascular disease, even when remnant cholesterol levels are defined, measured, or calculated in different ways. In-vitro and animal studies also support the contention that elevated...

  17. Cholesterol esterification during differentiation of mouse erythroleukemia (Friend) cells

    OpenAIRE

    Maria Franca Mulas; Antonella Mandas; Claudia Abete; Sandra Dessì; Alessandra Mocali; Francesco Paoletti

    2011-01-01

    Cholesterol is an essential constituent of all mammalian cell membranes, and its availability is therefore a prerequisite for cellular growth and other functions. Several lines of evidence are now indicating an association between alterations of cholesterol homeostasis and cell cycle progression. However, the role of cholesterol in cell differentiation is still largely unknown. To begin to address this issue, in this study we examined changes in cholesterol metabolism and in the mRNA levels o...

  18. Polymer sorbent with the properties of an artificial cholesterol receptor

    Science.gov (United States)

    Polyakova, I. V.; Ezhova, N. M.; Osipenko, A. A.; Pisarev, O. A.

    2015-02-01

    A cholesterol-imprinted polymer sorbent and the corresponding reticular control copolymer were synthesized from hydroxyethyl methacrylate and ethyleneglycol dimethacrylate. The sorption isotherms of cholesterol were analyzed using the generalized Langmuir and Freundlich equations. In the case of the imprinted reticular polymer, cholesterol sorption occurred on the energetically homogeneous binding centers, forming one monolayer, while the nonspecific sorption of cholesterol on the control copolymer occurred with energetically nonhomogeneous binding of the sorbate and depended on the physicochemical conditions of sorption.

  19. Ezetimibe and Simvastatin Reduce Cholesterol Levels in Zebrafish Larvae Fed a High-Cholesterol Diet

    Directory of Open Access Journals (Sweden)

    Ji Sun Baek

    2012-01-01

    Full Text Available Cholesterol-fed zebrafish is an emerging animal model to study metabolic, oxidative, and inflammatory vascular processes relevant to pathogenesis of human atherosclerosis. Zebrafish fed a high-cholesterol diet (HCD develop hypercholesterolemia and are characterized by profound lipoprotein oxidation and vascular lipid accumulation. Using optically translucent zebrafish larvae has the advantage of monitoring vascular pathology and assessing the efficacy of drug candidates in live animals. Thus, we investigated whether simvastatin and ezetimibe, the principal drugs used in management of hypercholesterolemia in humans, would also reduce cholesterol levels in HCD-fed zebrafish larvae. We found that ezetimibe was well tolerated by zebrafish and effectively reduced cholesterol levels in HCD-fed larvae. In contrast, simvastatin added to water was poorly tolerated by zebrafish larvae and, when added to food, had little effect on cholesterol levels in HCD-fed larvae. Combination of low doses of ezetimibe and simvastatin had an additive effect in reducing cholesterol levels in zebrafish. These results suggest that ezetimibe exerts in zebrafish a therapeutic effect similar to that in humans and that the hypercholesterolemic zebrafish can be used as a low-cost and informative model for testing new drug candidates and for investigating mechanisms of action for existing drugs targeting dyslipidemia.

  20. Cholesterol Assimilation by Lactobacillus Probiotic Bacteria: An In Vitro Investigation

    OpenAIRE

    Catherine Tomaro-Duchesneau; Mitchell L. Jones; Divya Shah; Poonam Jain; Shyamali Saha; Satya Prakash

    2014-01-01

    Excess cholesterol is associated with cardiovascular diseases (CVD), an important cause of mortality worldwide. Current CVD therapeutic measures, lifestyle and dietary interventions, and pharmaceutical agents for regulating cholesterol levels are inadequate. Probiotic bacteria have demonstrated potential to lower cholesterol levels by different mechanisms, including bile salt hydrolase activity, production of compounds that inhibit enzymes such as 3-hydroxy-3-methylglutaryl coenzyme A, and ch...

  1. CHROMATOGRAPHIC METHODS IN THE ANALYSIS OF CHOLESTEROL AND RELATED LIPIDS

    NARCIS (Netherlands)

    HOVING, EB

    1995-01-01

    Methods using thin-layer chromatography, solid-phase extraction, gas chromatography, high-performance liquid chromatography and supercritical fluid chromatography are described for the analysis of single cholesterol, esterified and sulfated cholesterol, and for cholesterol in the context of other li

  2. Hypercholesterolemia: The Role of Schools in Cholesterol Screening.

    Science.gov (United States)

    Price, James H.; Casler, Suzanne M.

    1997-01-01

    Examines the prevalence of cardiovascular disease risk factors among children and adolescents, the pros and cons of cholesterol screening among youth, cholesterol assessments of at-risk youth, and the role of schools in cholesterol education and screening (focusing on comprehensive school health education and services). (SM)

  3. Porcine artery elastin preparation reduces serum cholesterol level in rats

    OpenAIRE

    Liyanage, Ruvini; Nakamura, Yumi; Shimada, Ken-ichiro; SEKIKAWA, Mitsuo; Jayawardana, Barana Chaminda; HAN, Kyu-Ho; Tomoko, Okada; Ohba, Kiyoshi; Takahata, Yoshihisa; Morimatsu, Fumiki; FUKUSHIMA, Michihiro; 福島, 道広; 島田, 謙一郎; 関川, 三男; 韓, 圭鎬

    2009-01-01

    The effect of porcine artery elastin on serum cholesterol level was investigated in rats fed a cholesterol-free diet. Rats were fed for 4 weeks, with a diet (ED) containing 15% casein and 5% of porcine artery elastin in comparison with a diet (CD) containing 20% casein. The total serum and non-HDL-cholesterol concentrations were lower (P

  4. Emerging roles of the intestine in control of cholesterol metabolism

    NARCIS (Netherlands)

    J.K. Kruit; A.K. Groen; T.J. van Berkel; F. Kuipers

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis, clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor t

  5. On the puzzling distribution of cholesterol in the plasma membrane.

    Science.gov (United States)

    Giang, H; Schick, M

    2016-09-01

    The distribution of cholesterol between the two leaves of the plasma membrane in mammalian cells presents a conundrum; given cholesterol's known affinity for sphingomyelin, which resides predominantly in the exoplasmic leaf, why is it that experiment finds a majority of the cholesterol in the cytoplasmic leaf? This article reviews a recently proposed solution to this puzzle. PMID:26724709

  6. Alcohol consumption stimulates early steps in reverse cholesterol transport

    NARCIS (Netherlands)

    Gaag, M.S. van der; Tol, A. van; Vermunt, S.H.F.; Scheek, L.M.; Schaafsma, G.; Hendriks, H.F.J.

    2001-01-01

    Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol pathw

  7. Effects of Cholesterol-altering Pharmaceuticals on Cholesterol Metabolism, Steroidogenesis, and Gene Expression in the Fathead Minnow (Pimephales promelas)

    Science.gov (United States)

    Pharmaceuticals that target cholesterol biosynthesis and uptake are among the most widely prescribed drugs and have been detected in the aquatic environment. Fibrates are a class of pharmaceuticals that indirectly modulate cholesterol biosynthesis through effects on peroxisome pr...

  8. Immobilization of cholesterol esterase and cholesterol oxidase onto sol-gel films for application to cholesterol biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Suman [Central Mechanical Engineering Research Institute, G. Avenue, Durgapur 713209, West Bengal (India); Singhal, Rahul [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012 (India); Malhotra, B.D. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012 (India)]. E-mail: bansi.malhotra@gmail.com

    2007-01-23

    Cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) have been covalently immobilized onto tetraethylorthosilicate (TEOS) sol-gel films. The tetraethylorthosilicate sol-gel/ChEt/ChOx enzyme films thus prepared have been characterized using scanning electron microscopic (SEM), UV-vis spectroscopic, Fourier-transform-infrared (FTIR) spectroscopic and amperometric techniques, respectively. The results of photometric measurements carried out on tetraethylorthosilicate sol-gel/ChEt/ChOx reveal thermal stability up to 55 deg. C, response time as 180 s, linearity up to 780 mg dL{sup -1} (12 mM), shelf life of 1 month, detection limit of 12 mg dL{sup -1} and sensitivity as 5.4 x 10{sup -5} Abs. mg{sup -1} dL{sup -1}.

  9. Understanding Cholesterol and Heart Health | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... this page please turn Javascript on. Feature: High Cholesterol Understanding Cholesterol and Heart Health Past Issues / Summer 2012 Table ... both types of lipoproteins is important. High Blood Cholesterol and Triglycerides High blood cholesterol is a condition ...

  10. Effect of testosterone deficiency on cholesterol metabolism in pigs fed a high-fat and high-cholesterol diet

    OpenAIRE

    Cai, Zhaowei; Xi, Haitao; Pan, Yongming; Jiang, Xiaoling; Chen, Liang; Cai, Yueqin; Zhu, Keyan; Chen, Cheng; XU, XIAOPING; Chen, Minli

    2015-01-01

    Background Testosterone deficiency is associated with increased serum cholesterol levels. However, how testosterone deficiency precisely affects cholesterol metabolism remains unclear. Therefore, in the current study, we examined the effect of testosterone deficiency on cholesterol metabolism and liver gene expression in pigs fed a high-fat and high-cholesterol (HFC) diet. Methods Sexually mature male miniature pigs (6–7 months old) were randomly divided into 3 groups as follows: intact male ...

  11. Accessibility of Cholesterol in Endoplasmic Reticulum Membranes and Activation of SREBP-2 Switch Abruptly at a Common Cholesterol Threshold

    OpenAIRE

    Sokolov, Anna; Radhakrishnan, Arun

    2010-01-01

    Recent studies have shown that cooperative interactions in endoplasmic reticulum (ER) membranes between Scap, cholesterol, and Insig result in switch-like control over activation of SREBP-2 transcription factors. This allows cells to rapidly adjust rates of cholesterol synthesis and uptake in response to even slight deviations from physiological set-point levels, thereby ensuring cholesterol homeostasis. In the present study we directly probe for the accessibility of cholesterol in purified E...

  12. Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol

    NARCIS (Netherlands)

    R.P.F. Dullaart (Robin); A. Groen (Albert); G.M. Dallinga-Thie (Geesje); R. de Vries (Rindert); W. Sluiter (Wim); A. van Tol (Arie)

    2008-01-01

    textabstractObjective: We tested whether in metabolic syndrome (MetS) subjects the ability of plasma to stimulate cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport pathway, is maintained despite low high-density lipoprotein (HDL) cholesterol. Design: In

  13. Is the FXR the fix for cholesterol gallstone disease?

    Science.gov (United States)

    Juran, Brian D; Lazaridis, Konstantinos N

    2005-07-01

    Cholesterol gallstone disease is characterized by several events, including cholesterol precipitation in bile, increased bile salt hydrophobicity and gallbladder inflammation. Here, we describe the same phenotype in mice lacking the bile acid receptor, FXR. Furthermore, in susceptible wild-type mice that recapitulate human cholesterol gallstone disease, treatment with a synthetic FXR agonist prevented sequelae of the disease. These effects were mediated by FXR-dependent increases in biliary bile salt and phospholipid concentrations, which restored cholesterol solubility and thereby prevented gallstone formation. Taken together, these results indicate that FXR is a promising therapeutic target for treating or preventing cholesterol gallstone disease. PMID:15962294

  14. [HDL cholesterol as a sensitive diagnostic parameter in malaria].

    Science.gov (United States)

    Kittl, E M; Diridl, G; Lenhart, V; Neuwald, C; Tomasits, J; Pichler, H; Bauer, K

    1992-01-01

    In patients with malaria the lipid parameters triglycerides, cholesterol, and HDL-cholesterol were determined routinely. At the time of admission hypertriglyceridemia, hypocholesterolemia, and an extreme decrease in HDL-cholesterol were found. This dyslipoproteinemia was present in cases of falciparum malaria, as well as in cases of benign tertian malaria. The extent of HDL-cholesterol decrease showed no correlation to the severity of the clinical course of disease. HDL-cholesterol has proven to be an independent diagnostic laboratory finding in cases of suspected malarial infection. This parameter displays high diagnostic sensitivity, but no specificity for malaria. PMID:1546481

  15. Biochemical and Bioimaging Evidence of Cholesterol in Acquired Cholesteatoma

    DEFF Research Database (Denmark)

    Thorsted, Bjarne; Bloksgaard, Maria; Groza, Alexandra;

    2016-01-01

    results show that the total lipid content of the cholesteatoma matrix is similar to that of stratum corneum from skin and that the cholesteatoma matrix unquestionably contains cholesterol. The cholesterol content in the cholesteatoma matrix is increased by over 30% (w/w dry weight) compared to the control....... The cholesterol sulfate content is below 1% of the total lipids in both the cholesteatoma and the control. Cholesterol ester was reduced by over 30% when compared to the control. CONCLUSIONS: The content of cholesterol in the cholesteatoma matrix is significantly different from that in stratum corneum...

  16. Common Force Field Thermodynamics of Cholesterol

    OpenAIRE

    Francesco Giangreco; Eiji Yamamoto; Yoshinori Hirano; Milan Hodoscek; Volker Knecht; Matteo di Giosia; Matteo Calvaresi; Francesco Zerbetto; Kenji Yasuoka; Tetsu Narumi; Masato Yasui; Siegfried Höfinger

    2013-01-01

    Four different force fields are examined for dynamic characteristics using cholesterol as a case study. The extent to which various types of internal degrees of freedom become thermodynamically relevant is evaluated by means of principal component analysis. More complex degrees of freedom (angle bending, dihedral rotations) show a trend towards force field independence. Moreover, charge assignments for membrane-embedded compounds are revealed to be critical with significant impact on biologic...

  17. Cholesterol crystal embolisation to the alimentary tract.

    OpenAIRE

    Moolenaar, W; Lamers, C B

    1996-01-01

    The features of cholesterol crystal embolisation (CCE) to the alimentary tract were studied by retrospective analysis of the clinical and pathological data of 96 patients (70 men, 26 women, mean age 73.8 (58-95) years) with this diagnosis in the Dutch national pathology information system (Pathologisch Anatomisch Landelijk Geautomatiseerd Archief (PALGA)) from 1973-92. In the 96 patients, 130 CCE sites were found throughout the alimentary tract, mostly in the colon (42.3%). Most patients had ...

  18. Potent and selective mediators of cholesterol efflux

    Energy Technology Data Exchange (ETDEWEB)

    Bielicki, John K; Johansson, Jan

    2015-03-24

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  19. Individual variation in serum cholesterol levels.

    OpenAIRE

    Hegsted, D. M.; Nicolosi, R J

    1987-01-01

    The intraindividual variances in serum/plasma cholesterol levels from a variety of sources have been examined. It is apparent that these are very substantial with mean coefficients of variation usually between 5% and 10%, even when the diet is controlled in metabolic studies. Some subjects show extreme variability from one blood sample to the next. Thus, it is very difficult to assess the degree of risk of individuals according to the guidelines provided by the Consensus Conference on lowerin...

  20. The Triglyceride-to-HDL Cholesterol Ratio

    OpenAIRE

    Giannini, Cosimo; Santoro, Nicola; Caprio, Sonia; Kim, Grace; Lartaud, Derek; Shaw, Melissa; Pierpont, Bridget; Weiss, Ram

    2011-01-01

    OBJECTIVE We evaluated whether the triglyceride-to-HDL cholesterol (TG/HDL-C) ratio is associated with insulin resistance (IR) in a large multiethnic cohort of obese youths. RESEARCH DESIGN AND METHODS Obese youths (1,452) had an oral glucose tolerance test and a fasting lipid profile. Insulin sensitivity was estimated using the whole body insulin sensitivity index (WBISI) and homeostasis model assessment (HOMA)-IR and evaluated, in a subgroup of 146 obese youths, by the hyperinsulinemic-eugl...

  1. HDL Cholesterol and Risk of Type 2 Diabetes

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Nordestgaard, Børge G;

    2015-01-01

    Observationally, low levels of HDL cholesterol are consistently associated with increased risk of type 2 diabetes. Therefore, plasma HDL cholesterol increasing has been suggested as a novel therapeutic option to reduce the risk of type 2 diabetes. Whether levels of HDL cholesterol are causally...... associated with type 2 diabetes is unknown. In a prospective study of the general population (n = 47,627), we tested whether HDL cholesterol-related genetic variants were associated with low HDL cholesterol levels and, in turn, with an increased risk of type 2 diabetes. HDL cholesterol-decreasing gene scores...... and allele numbers associated with up to -13 and -20% reductions in HDL cholesterol levels. The corresponding theoretically predicted hazard ratios for type 2 diabetes were 1.44 (95% CI 1.38-1.52) and 1.77 (1.61-1.95), whereas the genetic estimates were nonsignificant. Genetic risk ratios for type 2...

  2. Adrenal scanning with 131I-19-cholesterol

    International Nuclear Information System (INIS)

    The purpose of this paper is to describe our clinical experience of adrenal scanning with 131I-19-cholesterol and discuss its clinical usefulness. Adrenal scanning was performed for 21 patients with hypertension. One millicurie of 131I-19-cholesterol was injected intravenously and adrenal scannings were taken 6 to 11 days after injection with a rectilinear scanner or a gamma camera. No patient had an untoward reaction to the radiopharmaceutical. Confirmed diagnosis was obtained in 7 of 21 patients, i.e., 3 cases of primary aldosteronism, 1 idiopathic aldosteronism, 1 Cushing's syndrome and 2 cases of the essential hypertension. Among all of the primary aldosteronism and Cushing's syndrome, adrenal scanning gave clear evidence of concentration of radioactivity at the site of tumor. In the idiopathic aldosteronism of our study, uptake of radioactivity was brightly visible on the right, while uptake by the left gland was inhibited, so this case was diagnosed incorrectly as primary aldosteronism. The kidney scan with 203Hg-chlormerodrin obtained without moving the patient after an adrenal scan was very useful for getting information of anatomical site of the activity. The effective half-life was calculated as 1.83 days by means of sequential profile whole-body scannings, and the total-body absorbed radiation dose was estimated as 0.65 rad/mCi by using MIRD pamphlets. Our conclusion is that the adrenal scanning with 131I-19-cholesterol is very useful for localization of the functional adrenal cortical tumor. (author)

  3. Mitochondrial cholesterol: mechanisms of import and effects on mitochondrial function.

    Science.gov (United States)

    Martin, Laura A; Kennedy, Barry E; Karten, Barbara

    2016-04-01

    Mitochondria require cholesterol for biogenesis and membrane maintenance, and for the synthesis of steroids, oxysterols and hepatic bile acids. Multiple pathways mediate the transport of cholesterol from different subcellular pools to mitochondria. In steroidogenic cells, the steroidogenic acute regulatory protein (StAR) interacts with a mitochondrial protein complex to mediate cholesterol delivery to the inner mitochondrial membrane for conversion to pregnenolone. In non-steroidogenic cells, several members of a protein family defined by the presence of a StAR-related lipid transfer (START) domain play key roles in the delivery of cholesterol to mitochondrial membranes. Subdomains of the endoplasmic reticulum (ER), termed mitochondria-associated ER membranes (MAM), form membrane contact sites with mitochondria and may contribute to the transport of ER cholesterol to mitochondria, either independently or in conjunction with lipid-transfer proteins. Model systems of mitochondria enriched with cholesterol in vitro and mitochondria isolated from cells with (patho)physiological mitochondrial cholesterol accumulation clearly demonstrate that mitochondrial cholesterol levels affect mitochondrial function. Increased mitochondrial cholesterol levels have been observed in several diseases, including cancer, ischemia, steatohepatitis and neurodegenerative diseases, and influence disease pathology. Hence, a deeper understanding of the mechanisms maintaining mitochondrial cholesterol homeostasis may reveal additional targets for therapeutic intervention. Here we give a brief overview of mitochondrial cholesterol import in steroidogenic cells, and then focus on cholesterol trafficking pathways that deliver cholesterol to mitochondrial membranes in non-steroidogenic cells. We also briefly discuss the consequences of increased mitochondrial cholesterol levels on mitochondrial function and their potential role in disease pathology. PMID:25425472

  4. Preparation of cholesterol oxidase nanoparticles and their application in amperometric determination of cholesterol

    Energy Technology Data Exchange (ETDEWEB)

    Chawla, Sheetal; Rawal, Rachna; Sonia; Ramrati; Pundir, C. S., E-mail: pundircs@rediffmail.com [M. D. University, Department of Biochemistry (India)

    2013-09-15

    The nanoparticle (NP) aggregates of commercial cholesterol oxidase (ChOx) were prepared by desolvation method. The formation and characterization of ChOxNP aggregates were studied by transmission electron microscopy and scanning electron microscopy. NP aggregates were more stable, active and had a higher shelf life than that of free enzyme. An amperometric cholesterol biosensor was constructed by immobilizing ChOxNPs onto Au electrode. The biosensor showed optimum response within 8 s at pH 6.0 and 35 Degree-Sign C, when polarized at +0.27 V versus Ag/AgCl. The biosensor possesses high sensitivity and measures cholesterol concentrations as low as 1.56 mg/dl. The working linear range was 12.5-700 mg/dl for cholesterol. The biosensor was evaluated and employed for measurement of total cholesterol in human serum. The enzyme electrode lost 50 % of its initial activity during its regular use for 180 times over a period of 90 days when stored in 0.1 M sodium phosphate buffer, pH 7.0 at 4 Degree-Sign C.

  5. When cholesterol is not cholesterol: a note on the enzymatic determination of its concentration in model systems containing vegetable extracts

    Directory of Open Access Journals (Sweden)

    Pamplona Reinald

    2010-06-01

    Full Text Available Abstract Background Experimental evidences demonstrate that vegetable derived extracts inhibit cholesterol absorption in the gastrointestinal tract. To further explore the mechanisms behind, we modeled duodenal contents with several vegetable extracts. Results By employing a widely used cholesterol quantification method based on a cholesterol oxidase-peroxidase coupled reaction we analyzed the effects on cholesterol partition. Evidenced interferences were analyzed by studying specific and unspecific inhibitors of cholesterol oxidase-peroxidase coupled reaction. Cholesterol was also quantified by LC/MS. We found a significant interference of diverse (cocoa and tea-derived extracts over this method. The interference was strongly dependent on model matrix: while as in phosphate buffered saline, the development of unspecific fluorescence was inhibitable by catalase (but not by heat denaturation, suggesting vegetable extract derived H2O2 production, in bile-containing model systems, this interference also comprised cholesterol-oxidase inhibition. Several strategies, such as cholesterol standard addition and use of suitable blanks containing vegetable extracts were tested. When those failed, the use of a mass-spectrometry based chromatographic assay allowed quantification of cholesterol in models of duodenal contents in the presence of vegetable extracts. Conclusions We propose that the use of cholesterol-oxidase and/or peroxidase based systems for cholesterol analyses in foodstuffs should be accurately monitored, as important interferences in all the components of the enzymatic chain were evident. The use of adequate controls, standard addition and finally, chromatographic analyses solve these issues.

  6. In vitro cholesterol uptake by Lactobacillus delbrueckii subsp. bulgaricus isolates

    Directory of Open Access Journals (Sweden)

    Małgorzata Ziarno

    2009-06-01

    Full Text Available Background. Some researchers have indicated that Lactobacillus delbrueckii subsp. bulgaricus may provide additional health benefits, reduce serum cholesterol level, for example. The aim of this study was to determine cholesterol uptake by Lb. delbrueckii subsp. bulgaricus commercial yoghurt starter isolates in artificial GIT fluids. Material and methods. Lb. delbrueckii subsp. bulgaricus isolates were cultured in MRS broth and in artificial GIT fluids contained cholesterol at initial concentration ca. 560 µg/mL, as well as in MRS broth with cholesterol addition. Results. All Lb. delbrueckii subsp. bulgaricus showed ability to uptake of cholesterol from MRS broth and artificial GIT fluids. The isolates incubated in artificial gastric fluid removed the minimal amounts of cholesterol in comparison to the same isolates incubated in MRS broth. Only two isolates removed significantly more cholesterol from MRS broth that from duodenal fluid. The amount of removed cholesterol from artificial duodenal fluid ranged from 20 µg/mL to 78 µg/mL. All Lb. delbrueckii subsp. bulgaricus isolates survived worse in artificial GIT fluids than in MRS broth. The viability of Lb. delbrueckii subsp. bulgaricus in GIT fluids depended on isolate. Conclusions. These results proved that Lb. delbrueckii subsp. bulgaricus shows ability to uptake cholesterol from MRS broth and artificial GIT fluids, and the degree of cholesterol uptake depends on isolate and incubation environment. The ability of Lb. delbrueckii subsp. bulgaricus to survive in GIT varies according to the isolates and incubation environment.

  7. Cholesterol: Its Regulation and Role in Central Nervous System Disorders

    Directory of Open Access Journals (Sweden)

    Matthias Orth

    2012-01-01

    Full Text Available Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer’s disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules. We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions.

  8. Potassium-doped carbon nanotubes toward the direct electrochemistry of cholesterol oxidase and its application in highly sensitive cholesterol biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiaorong [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Xu Jingjuan, E-mail: xujj@nju.edu.cn [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Chen Hongyuan [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China)

    2011-10-30

    We demonstrate herein a newly developed serum total cholesterol biosensor by using the direct electron transfer of cholesterol oxidase (ChOx), which is based on the immobilization of cholesterol oxidase and cholesterol esterase (ChEt) on potassium-doped multi-walled carbon nanotubes (KMWNTs) modified electrodes. The KMWNTs accelerate the electron transfer from electrode surface to the immobilized ChOx, achieving the direct electrochemistry of ChOx and maintaining its bioactivity. As a new platform in cholesterol analysis, the resulting electrode (ChOx/KMWNTs/GCE) exhibits a sensitive response to free cholesterol, with a linear range of 0.050-16.0 {mu}mol L{sup -1} and a detection limit of 5.0 nmol L{sup -1} (S/N = 3). Coimmobilization of ChEt and ChOx (ChEt/ChOx/KMWNTs/GCE) allows the determination of both free cholesterol and esterified cholesterol. The resulting biosensor shows the same linear range of 0.050-16.0 {mu}mol L{sup -1} for free cholesterol and cholesteryl oleate, with the detection limit of 10.0 and 12.0 nmol L{sup -1} (S/N = 3), respectively. The concentrations of total (free and esterified) cholesterol in human serum samples, determined by using the techniques developed in the present study, are in good agreement with those determined by the well-established techniques using the spectrophotometry.

  9. Effect of dietary Maitake (Grifola frondosa) mushrooms on plasma cholesterol and hepatic gene expression in cholesterol-fed mice.

    Science.gov (United States)

    Sato, Mayumi; Tokuji, Yoshihiko; Yoneyama, Shozo; Fujii-Akiyama, Kyoko; Kinoshita, Mikio; Chiji, Hideyuki; Ohnishi, Masao

    2013-01-01

    To investigate the effects of dietary Grifola frondosa on cholesterol, normal mice were fed a diet containing 1% cholesterol (HC group) or 1% cholesterol and 10% freeze-dried G. frondosa powder (HC+G group) for 4 weeks and hepatic and plasma lipid levels were compared with those of a cholesterol-free diet-fed mice (N group). Hepatic total cholesterol (TC), triacylglycerol contents were considerably increased and plasma TC / phospholipid (PL) was also increased significantly in the HC group compared with the N group. However, plasma TC content decreased in the HC+G group compared with the HC group. To characterize the mechanisms responsible for lowered plasma cholesterol in G. frondosa-supplemented mice, hepatic gene expression was profiled using DNA microarray and gene ontology. Genome analyses revealed that de novo cholesterol synthesis genes were suppressed following cholesterol intake. However, expression of bile acid biosynthesis and low-density lipoprotein receptor genes showed little change. Scarb1, Abcg5, and Abcg8, involved in cholesterol transport and excretion, were slightly upregulated in the HC+G group compared with the HC group. These data indicate the plasma cholesterol-lowering effect of G. frondosa. Moreover, fatty acid (FA) β-oxidation was promoted via adipocytokine signaling pathways, and Saa, encodes serum amyloid A related to arteriosclerosis, was suppressed in the HC+G group. PMID:24292357

  10. Preparation of intravenous cholesterol tracer using current good manufacturing practices.

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B; Swaney, William P; Ostlund, Richard E

    2015-12-01

    Studies of human reverse cholesterol transport require intravenous infusion of cholesterol tracers. Because insoluble lipids may pose risk and because it is desirable to have consistent doses of defined composition available over many months, we investigated the manufacture of cholesterol tracer under current good manufacturing practice (CGMP) conditions appropriate for phase 1 investigation. Cholesterol tracer was prepared by sterile admixture of unlabeled cholesterol or cholesterol-d7 in ethanol with 20% Intralipid(®). The resulting material was filtered through a 1.2 micron particulate filter, stored at 4°C, and tested at time 0, 1.5, 3, 6, and 9 months for sterility, pyrogenicity, autoxidation, and particle size and aggregation. The limiting factor for stability was a rise in thiobarbituric acid-reacting substances of 9.6-fold over 9 months (P manufacturing methods can be achieved in the academic setting and need to be considered for critical components of future metabolic studies. PMID:26416797

  11. Transport of circulating serum cholesterol by human renal cell carcinoma

    International Nuclear Information System (INIS)

    Clear cell renal cancer contains a large quantity of cholesterol ester (300-mg./gm. protein). To determine whether abnormalities in cholesterol transport could account for this sterol accumulation, the uptake, release, and imaging capabilities of intravenously injected 131I-6-iodomethyl-29-norcholesterol, a cholesterol analogue, were studied preoperatively in five patients with clear cell renal cancer. At surgery, samples of the liver, tumor, adrenal, and non-tumor kidney were obtained for analysis. 131I-sterol uptake by the tumor, when normalized for cholesterol content, was less than for adrenal, liver or kidney. In contrast, release of preloaded 131I-sterol from the human tumors was consistently slower than for normal kidney. The reduced release of free cholesterol from renal cancer cells may, in part, be responsible for the accumulation of cholesterol in human renal cancer

  12. Cholesterol monohydrate nucleation in ultrathin films on water

    DEFF Research Database (Denmark)

    Rapaport, H.; Kuzmenko, I.; Lafont, S.;

    2001-01-01

    The growth of a cholesterol crystalline phase, three molecular layers thick at the air-water interface, was monitored by grazing incidence x-ray diffraction and x-ray reflectivity. Upon compression, a cholesterol film transforms from a monolayer of trigonal symmetry and low crystallinity to a...... trilayer, composed of a highly crystalline bilayer in a rectangular lattice and a disordered top cholesterol layer. This system undergoes a phase transition into a crystalline trilayer incorporating ordered water between the hydroxyl groups of the top and middle sterol layers in an arrangement akin to the...... triclinic 3-D crystal structure of cholesterol . H(2)O. By comparison, the cholesterol derivative stigmasterol transforms, upon compression, directly into a crystalline trilayer in the rectangular lattice. These results may contribute to an understanding of the onset of cholesterol crystallization in...

  13. Pairing of cholesterol with oxidized phospholipid species in lipid bilayers

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Loubet, Bastien; Olzynska, Agnieszka;

    2014-01-01

    We claim that (1) cholesterol protects bilayers from disruption caused by lipid oxidation by sequestering conical shaped oxidized lipid species such as 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PZPC) away from phospholipid, because cholesterol and the oxidized lipid have complementary...... shapes and (2) mixtures of cholesterol and oxidized lipids can self-assemble into bilayers much like lysolipid–cholesterol mixtures. The evidence for bilayer protection comes from molecular dynamics (MD) simulations and dynamic light scattering (DLS) measurements. Unimodal size distributions of extruded...... vesicles (LUVETs) made up of a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and PZPC containing high amounts of PZPC are only obtained when cholesterol is present in high concentrations. In simulations, bilayers containing high amounts of PZPC become porous, unless cholesterol is also present...

  14. Alterations of serum cholesterol and serum lipoprotein in breast cancer of women

    OpenAIRE

    Hasija, Kiran; Bagga, Hardeep K.

    2005-01-01

    Fasting blood sample of 50 normal subjects (control) and 100 patients of breast cancer were investigated for serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein, high density lipoprotein cholesterol:low density lipoprotein cholesterol ratio and total cholesterol:high density lipoprotein cholesterol ratio during breast cancer of women. Five cancer stages, types, age groups, parity and menopausal status were undertaken...

  15. Percentage of Adults with High Cholesterol Whose LDL Cholesterol Levels Are Adequately Controlled

    Science.gov (United States)

    ... non-missing response to cholesterol questionnaire. Exclusion Criteria: Pregnant women. Estimates for 18-39 year olds were not ... for only one type of service, such as dental or vision care. Persons covered by ... and Prevention, National Center for Health Statistics from the National ...

  16. Melittin-Lipid Bilayer Interactions and the Role of Cholesterol

    OpenAIRE

    Wessman, Per; Strömstedt, Adam A; Malmsten, Martin; Edwards, Katarina

    2008-01-01

    The membrane-destabilizing effect of the peptide melittin on phosphatidylcholine membranes is modulated by the presence of cholesterol. This investigation shows that inclusion of 40 mol % cholesterol in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine or 1,2-dioleoyl-sn-glycero-3-phosphocholine liposomes reduces melittin's affinity for the membrane. It is significant that the presence of cholesterol does not increase the amount of membrane-associated melittin needed to cause maximum leakage f...

  17. Interaction of Melittin with Membrane Cholesterol: A Fluorescence Approach

    OpenAIRE

    Raghuraman, H.; Chattopadhyay, Amitabha

    2004-01-01

    We have monitored the organization and dynamics of the hemolytic peptide melittin in membranes containing cholesterol by utilizing the intrinsic fluorescence properties of its functionally important sole tryptophan residue and circular dichroism spectroscopy. The significance of this study is based on the fact that the natural target for melittin is the erythrocyte membrane, which contains high amounts of cholesterol. Our results show that the presence of cholesterol inhibits melittin-induced...

  18. In vitro cholesterol uptake by Lactobacillus delbrueckii subsp. bulgaricus isolates

    OpenAIRE

    Małgorzata Ziarno

    2009-01-01

    Background. Some researchers have indicated that Lactobacillus delbrueckii subsp. bulgaricus may provide additional health benefits, reduce serum cholesterol level, for example. The aim of this study was to determine cholesterol uptake by Lb. delbrueckii subsp. bulgaricus commercial yoghurt starter isolates in artificial GIT fluids. Material and methods. Lb. delbrueckii subsp. bulgaricus isolates were cultured in MRS broth and in artificial GIT fluids contained cholesterol at initial con...

  19. Reverse cholesterol transport: From classical view to new insights

    OpenAIRE

    Astrid E van der Velde

    2010-01-01

    Cholesterol is of vital importance for the human body. It is a constituent for most biological membranes, it is needed for the formation of bile salts, and it is the precursor for steroid hormones and vitamin D. However, the presence of excess cholesterol in cells, and in particular in macrophages in the arterial vessel wall, might be harmful. The accumulation of cholesterol in arteries can lead to atherosclerosis, and in turn, to other cardiovascular diseases. The route that is primarily tho...

  20. Studies on PCSK9 in the regulation of cholesterol metabolism

    OpenAIRE

    Persson, Lena

    2011-01-01

    Elevated levels of plasma cholesterol, mainly in low density lipoproteins (LDL), are a major risk factor for coronary heart disease. The level of plasma LDL cholesterol (LDL-C) is largely dependent on the number of hepatic LDL receptors (LDLRs). Increased number of LDLRs leads to higher uptake of LDL particles and lower concentration of plasma LDL-C. Proprotein convertase subtilisin Kexin Type 9 (PCSK9) is a novel key regulator in cholesterol metabolism. PCSK9 reduces the numbe...

  1. Cholesterol esterification during differentiation of mouse erythroleukemia (Friend) cells.

    Science.gov (United States)

    Mulas, Maria Franca; Mandas, Antonella; Abete, Claudia; Dessì, Sandra; Mocali, Alessandra; Paoletti, Francesco

    2011-08-31

    Cholesterol is an essential constituent of all mammalian cell membranes and its availability is therefore a prerequisite for cellular growth and other functions. Several lines of evidence are now indicating an association between alterations of cholesterol homeostasis and cell cycle progression. However, the role of cholesterol in cell differentiation is still largely unknown. To begin to address this issue, in this study we examined changes in cholesterol metabolism and in the mRNA levels of proteins involved in cholesterol import and esterification (multi-drug resistance, MDR-3) and acylCoA: cholesterol acyltransferase (ACAT) and cholesterol export (caveolin-1) in Friend virus-induced erythroleukemia cells (MELC), in the absence or in the presence of the chemical inducer of differentiation, hexamethylene bisacetamide (HMBA). FBS-stimulated growth of MELC was accompanied by an immediate elevation of cholesterol synthesis and cholesterol esterification, and by an increase in the levels of MDR-3 and ACAT mRNAs. A decrease in caveolin-1 expression was also observed. However, when MELC were treated with HMBA, the inhibition of DNA synthesis caused by HMBA treatment, was associated with a decrease in cholesterol esterification and in ACAT and MDR-3 mRNA levels and an increase in caveolin-1 mRNA. Detection of cytoplasmic neutral lipids by staining MELC with oil red O, a dye able to evidence CE but not FC, revealed that HMBA-treatment also reduced growth-stimulated accumulation of cholesterol ester to approximately the same extent as the ACAT inhibitor, SaH. Overall, these results indicate for the first time a role of cholesterol esterification and of some related genes in differentiation of erythroid cells. PMID:22184540

  2. A review on lecithin:cholesterol acyltransferase deficiency.

    Science.gov (United States)

    Saeedi, Ramesh; Li, Min; Frohlich, Jiri

    2015-05-01

    Lecithin cholesterol acyl transferase (LCAT) is a plasma enzyme which esterifies cholesterol, and plays a key role in the metabolism of high-density lipoprotein cholesterol (HDL-C). Genetic disorders of LCAT are associated with lipoprotein abnormalities including low levels of HDL-C and presence of lipoprotein X, and clinical features mainly corneal opacities, changes in erythrocyte morphology and renal failure. Recombinant LCAT is being developed for the treatment of patients with LCAT deficiency. PMID:25172171

  3. Cholesterol esterification during differentiation of mouse erythroleukemia (Friend) cells

    Science.gov (United States)

    Mulas, Maria Franca; Mandas, Antonella; Abete, Claudia; Dessì, Sandra; Mocali, Alessandra; Paoletti, Francesco

    2011-01-01

    Cholesterol is an essential constituent of all mammalian cell membranes and its availability is therefore a prerequisite for cellular growth and other functions. Several lines of evidence are now indicating an association between alterations of cholesterol homeostasis and cell cycle progression. However, the role of cholesterol in cell differentiation is still largely unknown. To begin to address this issue, in this study we examined changes in cholesterol metabolism and in the mRNA levels of proteins involved in cholesterol import and esterification (multi-drug resistance, MDR-3) and acylCoA: cholesterol acyltransferase (ACAT) and cholesterol export (caveolin-1) in Friend virus-induced erythroleukemia cells (MELC), in the absence or in the presence of the chemical inducer of differentiation, hexamethylene bisacetamide (HMBA). FBS-stimulated growth of MELC was accompanied by an immediate elevation of cholesterol synthesis and cholesterol esterification, and by an increase in the levels of MDR-3 and ACAT mRNAs. A decrease in caveolin-1 expression was also observed. However, when MELC were treated with HMBA, the inhibition of DNA synthesis caused by HMBA treatment, was associated with a decrease in cholesterol esterification and in ACAT and MDR-3 mRNA levels and an increase in caveolin-1 mRNA. Detection of cytoplasmic neutral lipids by staining MELC with oil red O, a dye able to evidence CE but not FC, revealed that HMBA-treatment also reduced growth-stimulated accumulation of cholesterol ester to approximately the same extent as the ACAT inhibitor, SaH. Overall, these results indicate for the first time a role of cholesterol esterification and of some related genes in differentiation of erythroid cells. PMID:22184540

  4. Cholesterol esterification during differentiation of mouse erythroleukemia (Friend cells

    Directory of Open Access Journals (Sweden)

    Maria Franca Mulas

    2011-10-01

    Full Text Available Cholesterol is an essential constituent of all mammalian cell membranes, and its availability is therefore a prerequisite for cellular growth and other functions. Several lines of evidence are now indicating an association between alterations of cholesterol homeostasis and cell cycle progression. However, the role of cholesterol in cell differentiation is still largely unknown. To begin to address this issue, in this study we examined changes in cholesterol metabolism and in the mRNA levels of proteins involved in cholesterol import and esterification (multi-drug resistance, MDR-3 and acylCoA:cholesterol acyltransferase (ACAT and cholesterol export (caveolin-1 in Friend virus-induced erythroleukemia cells (MELC, in the absence or in the presence of the chemical inducer of differentiation, hexamethylene bisacetamide (HMBA. FBS-stimulated growth of MELC was accompanied by an immediate elevation of cholesterol synthesis and cholesterol esterification, and by an increase in the levels of MDR-3 and ACAT mRNAs. A decrease in caveolin-1 expression was also observed. However, when MELC were treated with HMBA, the inhibition of DNA synthesis caused by HMBA treatment, was associated with a decrease in cholesterol esterification and in ACAT and MDR-3 mRNA levels and an increase in caveolin-1 mRNA. Detection of cytoplasmic neutral lipids by staining MELC with oil red O, a dye able to evidence CE but not FC, revealed that HMBA-treatment also reduced growth-stimulated accumulation of cholesterol ester to approximately the same extent as the ACAT inhibitor, SaH. Overall, these results indicate for the first time a role of cholesterol esterification and of some related genes in differentiation of erythroid cells.

  5. Interaction of G protein coupled receptors and cholesterol.

    Science.gov (United States)

    Gimpl, Gerald

    2016-09-01

    G protein coupled receptors (GPCRs) form the largest receptor superfamily in eukaryotic cells. Owing to their seven transmembrane helices, large parts of these proteins are embedded in the cholesterol-rich plasma membrane bilayer. Thus, GPCRs are always in proximity to cholesterol. Some of them are functionally dependent on the specific presence of cholesterol. Over the last years, enormous progress on receptor structures has been achieved. While lipophilic ligands other than cholesterol have been shown to bind either inside the helix bundle or at the receptor-lipid interface, the binding site of cholesterol was either a single transmembrane helix or a groove between two or more transmembrane helices. A clear preference for one of the two membrane leaflets has not been observed. Not surprisingly, many hydrophobic residues (primarily leucine and isoleucine) were found to be involved in cholesterol binding. In most cases, the rough β-face of cholesterol contacted the transmembrane helix bundle rather than the surrounding lipid matrix. The polar hydroxy group of cholesterol was localized near the water-membrane interface with potential hydrogen bonding to residues in receptor loop regions. Although a canonical motif, designated as CCM site, was detected as a specific cholesterol binding site in case of the β2AR, this site was not found to be occupied by cholesterol in other GPCRs possessing the same motif. Cholesterol-receptor interactions can increase the compactness of the receptor structure and are able to enhance the conformational stability towards active or inactive receptor states. Overall, all current data suggest a high plasticity of cholesterol interaction sites in GPCRs. PMID:27108066

  6. CHOLESTEROL OXIDATION PRODUCTS IN MILK AND MILK PRODUCTS

    Directory of Open Access Journals (Sweden)

    A. Kemal SEÇKİN

    2004-02-01

    Full Text Available Cholesterol oxidation products (COPs are occurred by heat and light factors during processing, improper packaging and storage conditions. COPs are mutagenic, carcinogenity, cytotoxic, angiotoxic and damage to cell membrane and effect biosynthesis cholesterol in the metabolism . So, COPs have potential risk for public health. Also, in milk and milk products that have high cholesterol COPs can be also formed during processing and storage. Therefore it is necessary that measurements must be taken and standards must be in dairy about COPs.

  7. Cholesterol assimilation by Lactobacillus probiotic bacteria: an in vitro investigation.

    Science.gov (United States)

    Tomaro-Duchesneau, Catherine; Jones, Mitchell L; Shah, Divya; Jain, Poonam; Saha, Shyamali; Prakash, Satya

    2014-01-01

    Excess cholesterol is associated with cardiovascular diseases (CVD), an important cause of mortality worldwide. Current CVD therapeutic measures, lifestyle and dietary interventions, and pharmaceutical agents for regulating cholesterol levels are inadequate. Probiotic bacteria have demonstrated potential to lower cholesterol levels by different mechanisms, including bile salt hydrolase activity, production of compounds that inhibit enzymes such as 3-hydroxy-3-methylglutaryl coenzyme A, and cholesterol assimilation. This work investigates 11 Lactobacillus strains for cholesterol assimilation. Probiotic strains for investigation were selected from the literature: Lactobacillus reuteri NCIMB 11951, L. reuteri NCIMB 701359, L. reuteri NCIMB 702655, L. reuteri NCIMB 701089, L. reuteri NCIMB 702656, Lactobacillus fermentum NCIMB 5221, L. fermentum NCIMB 8829, L. fermentum NCIMB 2797, Lactobacillus rhamnosus ATCC 53103 GG, Lactobacillus acidophilus ATCC 314, and Lactobacillus plantarum ATCC 14917. Cholesterol assimilation was investigated in culture media and under simulated intestinal conditions. The best cholesterol assimilator was L. plantarum ATCC 14917 (15.18±0.55 mg/10(10) cfu) in MRS broth. L. reuteri NCIMB 701089 assimilated over 67% (2254.70±63.33 mg/10(10) cfu) of cholesterol, the most of all the strains, under intestinal conditions. This work demonstrates that probiotic bacteria can assimilate cholesterol under intestinal conditions, with L. reuteri NCIMB 701089 showing great potential as a CVD therapeutic. PMID:25295259

  8. Cholesterol Assimilation by Lactobacillus Probiotic Bacteria: An In Vitro Investigation

    Directory of Open Access Journals (Sweden)

    Catherine Tomaro-Duchesneau

    2014-01-01

    Full Text Available Excess cholesterol is associated with cardiovascular diseases (CVD, an important cause of mortality worldwide. Current CVD therapeutic measures, lifestyle and dietary interventions, and pharmaceutical agents for regulating cholesterol levels are inadequate. Probiotic bacteria have demonstrated potential to lower cholesterol levels by different mechanisms, including bile salt hydrolase activity, production of compounds that inhibit enzymes such as 3-hydroxy-3-methylglutaryl coenzyme A, and cholesterol assimilation. This work investigates 11 Lactobacillus strains for cholesterol assimilation. Probiotic strains for investigation were selected from the literature: Lactobacillus reuteri NCIMB 11951, L. reuteri NCIMB 701359, L. reuteri NCIMB 702655, L. reuteri NCIMB 701089, L. reuteri NCIMB 702656, Lactobacillus fermentum NCIMB 5221, L. fermentum NCIMB 8829, L. fermentum NCIMB 2797, Lactobacillus rhamnosus ATCC 53103 GG, Lactobacillus acidophilus ATCC 314, and Lactobacillus plantarum ATCC 14917. Cholesterol assimilation was investigated in culture media and under simulated intestinal conditions. The best cholesterol assimilator was L. plantarum ATCC 14917 (15.18 ± 0.55 mg/1010 cfu in MRS broth. L. reuteri NCIMB 701089 assimilated over 67% (2254.70 ± 63.33 mg/1010 cfu of cholesterol, the most of all the strains, under intestinal conditions. This work demonstrates that probiotic bacteria can assimilate cholesterol under intestinal conditions, with L. reuteri NCIMB 701089 showing great potential as a CVD therapeutic.

  9. New horizons for cholesterol ester transfer protein inhibitors.

    Science.gov (United States)

    Schwartz, Gregory G

    2012-02-01

    High-density lipoprotein (HDL) cholesterol levels bear an inverse relationship to cardiovascular risk. To date, however, no intervention specifically targeting HDL has been demonstrated to reduce cardiovascular risk. Cholesterol ester transfer protein (CETP) mediates transfer of cholesterol ester from HDL to apolipoprotein B-containing particles. Most, but not all observational cohort studies indicate that genetic polymorphisms of CETP associated with reduced activity and higher HDL cholesterol levels are also associated with reduced cardiovascular risk. Some, but not all studies indicate that CETP inhibition in rabbits retards atherosclerosis, whereas transgenic CETP expression in mice promotes atherosclerosis. Torcetrapib, the first CETP inhibitor to reach phase III clinical development, was abandoned due to excess mortality associated with increases in aldosterone and blood pressure. Two other CETP inhibitors have entered phase III clinical development. Anacetrapib is a potent inhibitor of CETP that produces very large increases in HDL cholesterol and large reductions in low-density lipoprotein (LDL) cholesterol, beyond those achieved with statins. Dalcetrapib is a less potent CETP inhibitor that produces smaller increases in HDL cholesterol with minimal effect on LDL cholesterol. Both agents appear to allow efflux of cholesterol from macrophages to HDL in vitro, and neither agent affects blood pressure or aldosterone in vivo. Two large cardiovascular outcomes trials, one with anacetrapib and one with dalcetrapib, should provide a conclusive test of the hypothesis that inhibition of CETP decreases cardiovascular risk. PMID:22083134

  10. Reconstitution of Cholesterol-Dependent Vaginolysin into Tethered Phospholipid Bilayers

    DEFF Research Database (Denmark)

    Budvytyte, Rima; Pleckaityte, M.; Zvirbliene, A.;

    2013-01-01

    Functional reconstitution of the cholesterol-dependent cytolysin vaginolysin (VLY) from Gardnerella vaginalis into artificial tethered bilayer membranes (tBLMs) has been accomplished. The reconstitution of VLY was followed in real-time by electrochemical impedance spectroscopy (EIS). Changes of the...... EIS parameters of the tBLMs upon exposure to VLY solutions were consistent with the formation of water-filled pores in the membranes. It was found that reconstitution of VLY is a strictly cholesterol-dependent, irreversible process. At a constant cholesterol concentration reconstitution of VLY...... platform for the detection of the activity of VLY and possibly other cholesterol-dependent cytolysins....

  11. Determination of cholesterol in human biliary calculus by TLC scanning

    Institute of Scientific and Technical Information of China (English)

    Yin Kang Yang; Kai Xiong Qiu; Yu Zhu Zhan; Er Yi Zhan; Hai Ming Yang; Ping Zheng

    2000-01-01

    AIM To study the physico-chemical properties of biliary calculus and the relationship between the calculusformation and the phase change of liquid crystal, providing the best evidence for the biliary calculusprevention and treatment.METHODS The cholesterol contents in thirty one cases of biliary calculus in Kunming were determined bydouble-wave-length TLC scanning with high efficiency silica gel films.RESULTS Under magnifiers, the granular biliary calculus from 31 patients were classified according totheir section structures and colours, as cholesterol cholelith, 25 cases; bilirubin cholelith, 4 cases andcompound cholelith, 2 cases. By TLC scanning, it was found that the content of cholesterol in human biliarycalculus was 71%- 100%, about 80% cholesterol bilestones whose cholesterol content was more than 90%being pure cholesterol bilestones.CONCLUSION Cholesterol bilestone is the main human biliary calculus in Kunming, which was inaccordance with X-ray analysis. Compared with the related reports, it is proved that the proportion ofcholesterol bilestones to biliary calculus is increasing because of the improved life standard and the decreaseof bilirubin bilestones resulted from bile duct ascariasis or bacteria infection in China since 90s, and that theincrease of cholesterol in-take leads to the increase of cholesterol metabolism disorder

  12. Cholesterol granuloma of the petrous apex: CT diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Lo, W.W.M.; Solti-Bohman, L.G.; Brackmann, D.E.; Gruskin, P.

    1984-12-01

    Cholesterol granuloma of the petrous apex is a readily recognizable and treatable entity that is more common than previously realized. Cholesterol granuloma grows slowly in the petrous apex as a mass lesion until it produces hearing loss, tinnitus, vertigo, and facial twitching. Twelve cases of cholesterol granuloma of the petrous apex are illustrated; ten of these analyzed in detail, especially with respect to CT findings. A sharply and smoothly marginated expansile lesion in the petrous apex, isodense with plain and nonenhancing on CT, is in all probability a cholesterol granuloma. Preoperative recognition by CT is important for planning proper treatment.

  13. Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport.

    Science.gov (United States)

    Kobayashi, T; Beuchat, M H; Lindsay, M; Frias, S; Palmiter, R D; Sakuraba, H; Parton, R G; Gruenberg, J

    1999-06-01

    The fate of free cholesterol released after endocytosis of low-density lipoproteins remains obscure. Here we report that late endosomes have a pivotal role in intracellular cholesterol transport. We find that in the genetic disease Niemann-Pick type C (NPC), and in drug-treated cells that mimic NPC, cholesterol accumulates in late endosomes and sorting of the lysosomal enzyme receptor is impaired. Our results show that the characteristic network of lysobisphosphatidic acid-rich membranes contained within multivesicular late endosomes regulates cholesterol transport, presumably by acting as a collection and distribution device. The results also suggest that similar endosomal defects accompany the anti-phospholipid syndrome and NPC. PMID:10559883

  14. Cholesterol epoxide is a direct-acting mutagen.

    OpenAIRE

    A. Sevanian; Peterson, A R

    1984-01-01

    A 24-hr treatment of V79 Chinese hamster lung fibroblasts with 12.4 microM cholesterol 5 alpha, 6 alpha-epoxide induced 8-azaguanine-resistant mutants at frequencies 4.6- to 11.8-fold higher than the spontaneous mutation rate. We show that cholesterol epoxide, which is produced by in vivo cholesterol oxidation, is a weak direct-acting mutagen. Cholesterol epoxide was found to be accumulated by cells and transformed to cholestane-3 beta, 5 alpha, 6 beta-triol, which was more toxic and a more p...

  15. High-density lipoprotein cholesterol: How High

    Directory of Open Access Journals (Sweden)

    G Rajagopal

    2012-01-01

    Full Text Available The high-density lipoprotein cholesterol (HDL-C is considered anti-atherogenic good cholesterol. It is involved in reverse transport of lipids. Epidemiological studies have found inverse relationship of HDL-C and coronary heart disease (CHD risk. When grouped according to HDL-C, subjects having HDL-C more than 60 mg/dL had lesser risk of CHD than those having HDL-C of 40-60 mg/dL, who in turn had lesser risk than those who had HDL-C less than 40 mg/dL. No upper limit for beneficial effect of HDL-C on CHD risk has been identified. The goals of treating patients with low HDL-C have not been firmly established. Though many drugs are known to improve HDL-C concentration, statins are proven to improve CHD risk and mortality. Cholesteryl ester transfer protein (CETP is involved in metabolism of HDL-C and its inhibitors are actively being screened for clinical utility. However, final answer is still awaited on CETP-inhibitors.

  16. Specific Ion Effects in Cholesterol Monolayers

    Directory of Open Access Journals (Sweden)

    Teresa Del Castillo-Santaella

    2016-05-01

    Full Text Available The interaction of ions with interfaces and, in particular, the high specificity of these interactions to the particular ions considered, are central questions in the field of surface forces. Here we study the effect of different salts (NaI, NaCl, CaCl2 and MgCl2 on monolayers made of cholesterol molecules, both experimentally (surface area vs. lateral pressure isotherms measured by a Langmuir Film Balance and theoretically (molecular dynamics (MD all-atomic simulations. We found that surface isotherms depend, both quantitatively and qualitatively, on the nature of the ions by altering the shape and features of the isotherm. In line with the experiments, MD simulations show clear evidences of specific ionic effects and also provide molecular level details on ion specific interactions with cholesterol. More importantly, MD simulations show that the interaction of a particular ion with the surface depends strongly on its counterion, a feature ignored so far in most theories of specific ionic effects in surface forces.

  17. Crystallogeny fundamentals of the cholesterol gallstone

    Institute of Scientific and Technical Information of China (English)

    Wu Jie; Zhou Jianli; He Lijun; Qu Xingang; Gu Lin; Yang Haimin

    2007-01-01

    The nucleation mechanism and crystal growth process of the cholesterol gallstone are studied and a systematic theory expounded by crystallogeny is proposed. Normal feed and stone-forming feed were used to raise guinea pigs in the control and stone-causing groups respectively. The state and transformation of liquid crystal vesicles, the appearance of crystal nuclei, and the formation of microcrystal grains were observed under a polarizing microscope during the experimental period. It was found that the liquid crystal vesicles in the bile of the control group were small, scattered, and always existed as single forms, and no shaped gallstone crystals were formed.While in the stone-causing group, liquid crystal vesicles grew to larger ones, and then aggregated to form large liquid crystal cells. Solid crystal growth along the edge of these liquid crystal cells formed microcrystal grains. These demonstrated that bile liquid crystal vesicles form the basic nuclei of cholesterol gallstone. Heterogeneous nucleation is the common process in the formation of crystal nuclei and crystal growth.

  18. Assessment of modes of action and efficacy of plasma cholesterol-lowering drugs : measurement of cholesterol absorption, cholesterol synthesis and bile acid synthesis and turnover using novel stable isotope techniques

    NARCIS (Netherlands)

    Stellaard, Frans; Kuipers, Folkert

    2005-01-01

    Several processes are involved in control of plasma cholesterol levels, e.g., intestinal cholesterol absorption, endogenous cholesterol synthesis and transport and bile acid synthesis. Adaptation of either of these processes allows the body to adapt to changes in dietary cholesterol intake. Disturba

  19. Cholesterol efflux via ATP-binding cassette transporter A1 (ABCA1) and cholesterol uptake via the LDL receptor influences cholesterol-induced impairment of beta cell function in mice

    NARCIS (Netherlands)

    Kruit, J. K.; Kremer, P. H. C.; Dai, L.; Tang, R.; Ruddle, P.; de Haan, W.; Brunham, L. R.; Verchere, C. B.; Hayden, M. R.

    2010-01-01

    Cellular cholesterol accumulation is an emerging mechanism for beta cell dysfunction in type 2 diabetes. Absence of the cholesterol transporter ATP-binding cassette transporter A1 (ABCA1) results in increased islet cholesterol and impaired insulin secretion, indicating that impaired cholesterol effl

  20. The hedgehog receptor patched is involved in cholesterol transport.

    Directory of Open Access Journals (Sweden)

    Michel Bidet

    Full Text Available BACKGROUND: Sonic hedgehog (Shh signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened. METHODOLOGY/PRINCIPAL FINDINGS: Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement of the intracellular cholesterol concentration induces Smoothened enrichment in the plasma membrane, which is a crucial step for the signaling activation. We found that binding of Shh protein to its receptor Patched, which involves Patched internalization, increases the intracellular concentration of cholesterol and decreases the efflux of a fluorescent cholesterol derivative (BODIPY-cholesterol from these cells. Treatment of fibroblasts with cyclopamine, an antagonist of Shh signaling, inhibits Patched expression and reduces BODIPY-cholesterol efflux, while treatment with the Shh pathway agonist SAG enhances Patched protein expression and BODIPY-cholesterol efflux. We also show that over-expression of human Patched in the yeast S. cerevisiae results in a significant boost of BODIPY-cholesterol efflux. Furthermore, we demonstrate that purified Patched binds to cholesterol, and that the interaction of Shh with Patched inhibits the binding of Patched to cholesterol. CONCLUSION/SIGNIFICANCE: Our results suggest that Patched may contribute to cholesterol efflux from cells, and to modulation of the intracellular cholesterol concentration. This activity is likely responsible for the inhibition of the enrichment of Smoothened in the plasma membrane, which is an important step in Shh pathway

  1. Cholesterol Check (A Cup of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2015-09-10

    High blood cholesterol is a risk factor for cardiovascular disease. This podcast discusses the importance of a healthy diet and regular cholesterol screening.  Created: 9/10/2015 by MMWR.   Date Released: 9/10/2015.

  2. CDC Vital Signs: High Blood Pressure and Cholesterol

    Science.gov (United States)

    ... 1.36 MB] Read the MMWR Science Clips High Blood Pressure and Cholesterol Out of Control Recommend on Facebook ... by County http://apps.nccd.cdc.gov/GISCVH2/ High Blood Pressure and High Cholesterol Among US Adults SOURCES: National ...

  3. Transport of cholesterol autoxidation products in rabbit lipoproteins

    International Nuclear Information System (INIS)

    Radiolabeled pure [4-14C] cholesterol was kept at 600C under air to autoxidize for 5 weeks, after which approximately 12% cholesterol oxidation products were formed. The mixture, suspended in gelatin, was given to rabbits by gastric gavage. Rabbits were killed 4, 24 and 48 h after treatment. Cholesterol and its autoxidation products were separated by thin-layer chromatography into 5 fractions and radioactivities of each fraction were measured. Percentages of each fraction of cholesterol oxidation products and cholesterol in the original mixture before administration and in the rabbit sera after administration were similar, suggesting that the rates of absorption of cholesterol oxidation products are not significantly different from that of cholesterol. Lipoproteins were fractioned by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each fraction in lipoproteins separated by thin layer chromatography showed that fractions containing cholestane-3β, 5α, 6β-triol, 7α- and 7β-hydroxycholesterol and 7-ketocholesterol were more selectively transported in VLDL, whereas most of the 25-hydroxycholesterol was present in LDL. HDL contained only minute amounts of cholesterol oxidation products. 22 refs

  4. Effect of honey on serum cholesterol and lipid values.

    Science.gov (United States)

    Münstedt, Karsten; Hoffmann, Sven; Hauenschild, Annette; Bülte, Michael; von Georgi, Richard; Hackethal, Andreas

    2009-06-01

    Small studies have suggested that honey benefits patients with high cholesterol concentrations. The present study aimed to confirm this finding in a larger group of subjects. Sixty volunteers with high cholesterol, stratified according to gender and hydroxymethylglutaryl-coenzyme A reductase inhibitor (statin) treatment (yes/no), were randomized to receive 75 g of honey solution or a honey-comparable sugar solution once daily over a period of 14 days. Baseline measurements, including body mass index (BMI) and lipid profile, were obtained, and subjects also completed dietary questionnaires and the Inventory for the Assessment of Negative Bodily Affect-Trait form (INKA-h) questionnaire. Measurements were repeated 2 weeks later. BMI and high-density lipoprotein (HDL) cholesterol values were significantly correlated (r = -0.487; P INKA-h scores and LDL cholesterol values were also significantly correlated (r = 0.273, P = .042). Neither solution influenced significantly cholesterol or triglyceride values in the total group; in women, however, the LDL cholesterol value increased in the sugar solution subgroup but not in the women taking honey. Although ingesting honey did not reduce LDL cholesterol values in general, women may benefit from substituting honey for sugar in their diet. Reducing the BMI lowers the LDL cholesterol value, and psychological interventions also seem important and merit further investigation. PMID:19627212

  5. Composition of and cholesterol in Araucana and commercial eggs.

    Science.gov (United States)

    Peterson, D W; Lilyblade, A; Clifford, C K; Ernst, R; Clifford, A J; Dunn, P

    1978-01-01

    Araucana eggs from six sources and commercial-type white eggs of two major supermarket brands and from the University of California flock were collected and analyzed for cholesterol content of the yolk. The yolks of Araucana eggs were significantly higher in cholesterol than those of commercial white eggs. PMID:563887

  6. Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Samia Hannaoui

    2014-11-01

    Full Text Available Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD: whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD.

  7. Cholesterol and Sphingomyelin-Containing Model Condensed Lipid Monolayers: Heterogeneities Involving Ordered Microdomains Assessed by Two Cholesterol Derivatives.

    Science.gov (United States)

    Lecompte, Marie-France; Gaibelet, Gérald; Lebrun, Chantal; Tercé, François; Collet, Xavier; Orlowski, Stéphane

    2015-11-01

    Lipid monolayers are often considered as model membranes, but they are also the physiologic lipid part of the peripheral envelope of lipoproteins and cytosolic lipid bodies. However, their structural organization is still rather elusive, in particular when both cholesterol and sphingomyelin are present. To investigate such structural organization of hemimembranes, we measured, using alternative current voltammetry, the differential capacitance of condensed phosphatidylcholine-based monolayers as a function of applied potential, which is sensitive to their lipid composition and molecular arrangement. Especially, monolayers containing both sphingomyelin and cholesterol, at 15% w/w, presented specific characteristics of the differential capacitance versus potential curves recorded, which was indicative of specific interactions between these two lipid components. We then compared the behavior of two cholesterol derivatives (at 15% w/w), 21-methylpyrenyl-cholesterol (Pyr-met-Chol) and 22-nitrobenzoxadiazole-cholesterol (NBD-Chol), with that of cholesterol when present in model monolayers. Indeed, these two probes were chosen because of previous findings reporting opposite behaviors within bilayer membranes regarding their interaction with ordered lipids, with only Pyr-met-Chol mimicking cholesterol well. Remarkably, in monolayers containing sphingomyelin or not, Pyr-met-Chol and NBD-Chol presented contrasting behaviors, and Pyr-met-Chol mimicked cholesterol only in the presence of sphingomyelin. These two observations (i.e., optimal amounts of sphingomyelin and cholesterol, and the ability to discriminate between Pyr-met-Chol and NBD-Chol) can be interpreted by the existence of heterogeneities including ordered patches in sphingomyelin- and cholesterol-containing monolayers. Since such monolayer lipid arrangement shares some properties with the raft-type lipid microdomains well-described in sphingomyelin- and cholesterol-containing bilayer membranes, our data thus

  8. Cholesterol interactions with ceramide and sphingomyelin.

    Science.gov (United States)

    García-Arribas, Aritz B; Alonso, Alicia; Goñi, Felix M

    2016-09-01

    Sphingolipids contain in their polar heads chemical groups allowing them to establish a complex network of H-bonds (through different OH and NHgroups) with other lipids in the bilayer. In the recent years the specific interaction of sphingomyelin (SM) with cholesterol (Chol) has been examined, largely in the context of the "lipid raft" hypothesis. Formation of SM-Ceramide (Cer) complexes, proposed to exist in cell membranes in response to stress, has also been described. More recently, a delicate balance of phase formation and transformation in ternary mixtures of SM, Chol and Cer, with mutual displacement of Chol and Cer from their interaction with SM is considered to exist. In addition, data demonstrating direct Chol-Cer interaction are becoming available. PMID:27132117

  9. Ursodeoxycholic Acid for the Treatment of Cholesterol Gallstones

    International Nuclear Information System (INIS)

    Cholesterol is the principal constituent of more than three quarters of gallstones. Pure cholesterol crystals are quite soft, and protein contributes importantly to the strength of cholesterol stones. The risk of gallstones does not correlate with total serum cholesterol levels, but it does correlate with decreased high-density lipoprotein cholesterol and increased triglyceride levels. At least 10 percent of adults have gallstones where female: male ratio of about 2:1 in the younger age groups with increasing prevalence with age. Nine patients with gallstones (6 females and 3 males) were included in the study. Patients were treated with ursodeoxycholic acids tablets in two oral doses, one after breakfast, and the other after dinner for 9 months. Ultrasound examination was repeated every 3 months. Re-examination by abdominal ultrasonography revealed that gallstone 1 cm or less in diameter disappeared within 6 months, and the largest stone 3.06 cm in diameter disappeared within 9 months.

  10. Reverse cholesterol transport: From classical view to new insights

    Directory of Open Access Journals (Sweden)

    Astrid E van der Velde

    2010-12-01

    Full Text Available Cholesterol is of vital importance for the human body. It is a constituent for most biological membranes, it is needed for the formation of bile salts, and it is the precursor for steroid hormones and vitamin D. However, the presence of excess cholesterol in cells, and in particular in macrophages in the arterial vessel wall, might be harmful. The accumulation of cholesterol in arteries can lead to atherosclerosis, and in turn, to other cardiovascular diseases. The route that is primarily thought to be responsible for the disposal of cholesterol is called reverse cholesterol transport (RCT. Therefore, RCT is seen as an interesting target for the development of drugs aimed at the prevention of atherosclerosis. Research on RCT has taken off in recent years. In this review, the classical concepts about RCT are discussed, together with new insights about this topic.

  11. SND1 overexpression deregulates cholesterol homeostasis in hepatocellular carcinoma.

    Science.gov (United States)

    Navarro-Imaz, Hiart; Rueda, Yuri; Fresnedo, Olatz

    2016-09-01

    SND1 is a multifunctional protein participating, among others, in gene transcription and mRNA metabolism. SND1 is overexpressed in cancer cells and promotes viability and tumourigenicity of hepatocellular carcinoma cells. This study shows that cholesterol synthesis is increased in SND1-overexpressing hepatoma cells. Neither newly synthesised nor extracellularly supplied cholesterol are able to suppress this increase; however, inhibition of cholesterol esterification reverted the activated state of sterol-regulatory element-binding protein 2 (SREBP2) and cholesterogenesis. These results highlight SND1 as a potential regulator of cellular cholesterol distribution and homeostasis in hepatoma cells, and support the rationale for the therapeutic use of molecules that influence cholesterol management when SND1 is overexpressed. PMID:27238764

  12. Enzymatic-fluorometric quantification of cholesterol in bovine milk

    DEFF Research Database (Denmark)

    Larsen, Torben

    2012-01-01

    The present paper describes an enzymatic–fluorometric method for the determination of cholesterol in milk and other opaque matrices. The initial step of the method is to liberate chemically and physically bound cholesterol from the milk fat globule membrane by enzymatic action. The method is able...... to discriminate between esterified and free cholesterol in milk. The analysis is cost effective and is developed to work directly on whole, fresh milk thereby eliminating time consuming and tedious pre-treatment procedures of the sample. More than 1000 milk samples were analysed on the day of...... sampling. The total concentration of milk cholesterol ranged from 80 to 756 μM (n = 1068; mean 351 μM). Milk cholesterol was significantly correlated to milk fat concentration as analysed by mid-infra red spectrometry (r = 0.630; n = 853) and by an enzymatic–fluorometric method (triacylglycerol) (r = 0...

  13. Cholesterol-induced protein sorting: an analysis of energetic feasibility

    DEFF Research Database (Denmark)

    Lundbaek, J A; Andersen, O S; Werge, T;

    2003-01-01

    transmembrane domain (TMD). M. S. Bretscher and S. Munro (SCIENCE: 261:1280-1281, 1993) therefore proposed a physical sorting mechanism based on the hydrophobic match between the proteins' TMD and the bilayer thickness, in which cholesterol would regulate protein sorting by increasing the lipid bilayer...... thickness. In this model, Golgi proteins with short TMDs would be excluded from cholesterol-enriched domains (lipid rafts) that are incorporated into transport vesicles destined for the plasma membrane. Although attractive, this model remains unproven. We therefore evaluated the energetic feasibility...... thickness per se, however, have only a modest effect on sorting; the major effect arises because cholesterol changes also the bilayer material properties, which augments the energetic penalty for incorporating short TMDs into cholesterol-enriched domains. We conclude that cholesterol-induced changes...

  14. Cholesterol-binding viral proteins in virus entry and morphogenesis.

    Science.gov (United States)

    Schroeder, Cornelia

    2010-01-01

    Up to now less than a handful of viral cholesterol-binding proteins have been characterized, in HIV, influenza virus and Semliki Forest virus. These are proteins with roles in virus entry or morphogenesis. In the case of the HIV fusion protein gp41 cholesterol binding is attributed to a cholesterol recognition consensus (CRAC) motif in a flexible domain of the ectodomain preceding the trans-membrane segment. This specific CRAC sequence mediates gp41 binding to a cholesterol affinity column. Mutations in this motif arrest virus fusion at the hemifusion stage and modify the ability of the isolated CRAC peptide to induce segregation of cholesterol in artificial membranes.Influenza A virus M2 protein co-purifies with cholesterol. Its proton translocation activity, responsible for virus uncoating, is not cholesterol-dependent, and the transmembrane channel appears too short for integral raft insertion. Cholesterol binding may be mediated by CRAC motifs in the flexible post-TM domain, which harbours three determinants of binding to membrane rafts. Mutation of the CRAC motif of the WSN strain attenuates virulence for mice. Its affinity to the raft-non-raft interface is predicted to target M2 protein to the periphery of lipid raft microdomains, the sites of virus assembly. Its influence on the morphology of budding virus implicates M2 as factor in virus fission at the raft boundary. Moreover, M2 is an essential factor in sorting the segmented genome into virus particles, indicating that M2 also has a role in priming the outgrowth of virus buds.SFV E1 protein is the first viral type-II fusion protein demonstrated to directly bind cholesterol when the fusion peptide loop locks into the target membrane. Cholesterol binding is modulated by another, proximal loop, which is also important during virus budding and as a host range determinant, as shown by mutational studies. PMID:20213541

  15. Correction of enhanced endothelial permeability by cessation of cholesterol feeding

    International Nuclear Information System (INIS)

    Changes in endothelial permeability and the transport of macromolecules may be important in the initiation and/or progression of atherosclerosis. We have previously shown, with a carotid artery preparation isolated in situ with intact adventitia, that long-term cholesterol feeding in rabbits will result in a seven- to tenfold increase in 125I albumin transport across the artery into the systemic circulation. The current studies were undertaken to determine whether this abnormality of enhanced permeability could be reversed by cessation of cholesterol feeding and correction of the hyperlipidemia. Two groups of rabbits were fed either a standard Rabbit Chow or a diet containing 1.5% cholesterol and 5.2% corn oil for 12 to 15 weeks. Another group of rabbits was given cholesterol for 12 to 15 weeks with change to standard rabbit chow for an additional 22 to 24 weeks after which albumin transport studies were then performed. Mean plasma cholesterol level after 12 to 15 weeks of cholesterol feeding was 2052 +/- 395 mg/dl. After the animals were withdrawn from the cholesterol diet for 22 to 24 weeks, the mean plasma cholesterol level decreased to 80 +/- 21 mg/dl. The mean plasma cholesterol value in chow-fed animals was 39 +/- 6 mg/dl. Perfusion studies were done with 125I-labeled albumin and plasma radioactivity served as a measure of transport across the carotid artery. The average level of albumin transport across the artery into venous blood in the cholesterol-fed animals (13,911 dpm/ml of plasma) was significantly greater than that of control animals (2049 dpm/ml of plasma)

  16. Resveratrol Protects Rabbits Against Cholesterol Diet-Induced Hyperlipidaemia.

    Science.gov (United States)

    Tanko, Y; Jimoh, A; Ahmed, A; Mohammed, A; Ayo, J O

    2016-01-01

    The excessive consumption of high cholesterol diet has been associated with an increased incidence oflipidaemia. Lipidaemia is enhanced by formation of oxidative stress, lipid peroxidation and hyperglycaemia. The aim ofthese experiments was to investigate the protective effect of resveratrol co-administered with cholesterol diet inducedhyperlipidaemia in rabbits. Thirty rabbits divided into six groups of five animal (group= 5) each: group 1 = normal control,group 2 = cholesterol diet/high fat diet group only (HFD), group 3 = resveratrol 200 mg/kg (R200), group 4 = resveratrol400 mg/kg (R400), group 5 = HFD + R200 and group 6 = HFD + R400. The normal group was fed with standard animalfeeds only; while the HFD groups were fed with standard animal feeds + cholesterol diet (10% Groundnut oil, 20%Groundnut mill and 2% cholesterol). Resveratrol-treated rabbits received resveratrol suspended in 10 g/Lcarboxymethylcellulose (CMC) and the control group received the vehicle only, CMC. The preparations were administeredfor 8 weeks of experimental protocol. At the end of the study period, the animals were sacrificed. Blood and plasma sampleswere collected. Serum evaluation of lipid profile such as total cholesterol (TC), triacylglycerol (Tg), low density lipoproteincholesterol (LDP-c) and high density lipoprotein cholesterol (HDL-c) were also assessed. The results obtained showsignificant (P < 0.05) decrease in total cholesterol (TC), Low density lipoprotein cholesterol (LDP-c), total triacylglyceroland an increase in high density lipoprotein cholesterol (HDL-c) in resveratrol treated groups compared to HFD group only.In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrationsand might be beneficial in treatment of hyperlipidemia and atherosclerosis. PMID:27574767

  17. Bacterial colonization of host cells in the absence of cholesterol.

    Directory of Open Access Journals (Sweden)

    Stacey D Gilk

    2013-01-01

    Full Text Available Reports implicating important roles for cholesterol and cholesterol-rich lipid rafts in host-pathogen interactions have largely employed sterol sequestering agents and biosynthesis inhibitors. Because the pleiotropic effects of these compounds can complicate experimental interpretation, we developed a new model system to investigate cholesterol requirements in pathogen infection utilizing DHCR24(-/- mouse embryonic fibroblasts (MEFs. DHCR24(-/- MEFs lack the Δ24 sterol reductase required for the final enzymatic step in cholesterol biosynthesis, and consequently accumulate desmosterol into cellular membranes. Defective lipid raft function by DHCR24(-/- MEFs adapted to growth in cholesterol-free medium was confirmed by showing deficient uptake of cholera-toxin B and impaired signaling by epidermal growth factor. Infection in the absence of cholesterol was then investigated for three intracellular bacterial pathogens: Coxiella burnetii, Salmonella enterica serovar Typhimurium, and Chlamydia trachomatis. Invasion by S. Typhimurium and C. trachomatis was unaltered in DHCR24(-/- MEFs. In contrast, C. burnetii entry was significantly decreased in -cholesterol MEFs, and also in +cholesterol MEFs when lipid raft-associated α(Vβ(3 integrin was blocked, suggesting a role for lipid rafts in C. burnetii uptake. Once internalized, all three pathogens established their respective vacuolar niches and replicated normally. However, the C. burnetii-occupied vacuole within DHCR24(-/- MEFs lacked the CD63-positive material and multilamellar membranes typical of vacuoles formed in wild type cells, indicating cholesterol functions in trafficking of multivesicular bodies to the pathogen vacuole. These data demonstrate that cholesterol is not essential for invasion and intracellular replication by S. Typhimurium and C. trachomatis, but plays a role in C. burnetii-host cell interactions.

  18. Cholesterol Levels: What You Need to Know | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... this page please turn Javascript on. Feature: High Cholesterol Cholesterol Levels: What You Need to Know Past Issues / Summer 2012 Table of Contents Measuring Cholesterol Levels Learn more at MedlinePlus: https://medlineplus.gov/ ...

  19. High Blood Cholesterol Q&A Dr. Michael Lauer | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... this page please turn Javascript on. Feature: High Cholesterol High Blood Cholesterol Q&A with Dr. Michael Lauer Past Issues / ... heavier and older, what does recent research on cholesterol and heart health tell us that Americans need ...

  20. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study123

    OpenAIRE

    Racette, Susan B.; Lin, Xiaobo; Lefevre, Michael; Spearie, Catherine Anderson; MOST, MARLENE M.; Ma, Lina; Ostlund, Richard E

    2009-01-01

    Background: Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain.

  1. The influence of cholesterol and biomass concentration on the uptake of cholesterol by Lactobacillus from MRS broth

    Directory of Open Access Journals (Sweden)

    Małgorzata Ziarno

    2007-06-01

    Full Text Available The aim of this study was the determination of some factors influence (i.e. the vitality of bacteria cells and the cholesterol concentration on the ability of selected Lactobacillus sp. to cholesterol uptake during culture in MRS broth. Three Lactobacillus strains (Lb. delbrueckii subsp. bulgaricus, Lb. acidophilus, Lb. casei isolated from commercial single species lyophilized dairy starter cultures and three Lactobacillus strains (Lb. plantarum, Lb. delbrueckii subsp. bulgaricus, Lb. acidophilus originated from commercial pharmaceuticals were used in this study. The uptake of cholesterol from MRS broth during the growth of Lactobacillus sp., expressed as the difference between the final and the initial concentrations of cholesterol, ranged from 0.053 to 0.153 g/dm³, apart from the initial cholesterol content and the origin of Lactobacillus sp. The results confirmed that biomass concentration have a statistically significant effect on uptake of cholesterol. The ten-fold increase of the amount of intact cells biomass caused about 1.5-2-fold increase of the amount of cholesterol removed. The influence of the concentration of biomass of alive cells on the removal of cholesterol was bigger than in case of the heat-sterilized cells.

  2. How cholesterol interacts with membrane proteins: an exploration of cholesterol-binding sites including CRAC, CARC and tilted domains

    Directory of Open Access Journals (Sweden)

    FranciscoJBarrantes

    2013-02-01

    Full Text Available The plasma membrane of eukaryotic cells contains several types of lipids displaying high biochemical variability in both their apolar moiety (e.g. the acyl chain of glycerolipids and their polar head (e.g. the sugar structure of glycosphingolipids. Among these lipids, cholesterol is unique because its biochemical variability is almost exclusively restricted to the oxidation of its polar -OH group. Although generally considered the most rigid membrane lipid, cholesterol can adopt a broad range of conformations due to the flexibility of its isooctyl chain linked to the polycyclic sterane backbone. Moreover, cholesterol is an asymmetric molecule displaying a planar face and a rough  face. Overall, these structural features open up a number of possible interactions between cholesterol and membrane lipids and proteins, consistent with the prominent regulatory functions that this unique lipid exerts on membrane components. The aim of this review is to describe how cholesterol interacts with membrane lipids and proteins at the molecular/atomic scale, with special emphasis on transmembrane domains of proteins containing either the consensus cholesterol-binding motifs CRAC and CARC or a tilted peptide. Despite their broad structural diversity, all these domains bind cholesterol through common molecular mechanisms, leading to the identification of a subset of amino acid residues that are overrepresented in both linear and three-dimensional membrane cholesterol-binding sites.

  3. Incorporation of 4-14C labeled cholesterol into the cholesterol ester fractions of plasma lipoproteins in patients with cirrhosis of the liver

    International Nuclear Information System (INIS)

    In vivo incorporation studies with 4-14C-cholesterol were performed in five patients cirrhosis of the liver. All patients showed low concentrations of total cholesterol, esterified cholesterol, and a low activity of the lecithin:cholesterol acyltransferase activity (LCAT). The pattern of incorporation corresponded to the results known from hypercholesterolemic, normocholesterolemic and hypertriglyceridemic patients. Low cholesterol ester concentrations and low LCAT activity do not modify the pattern of incorporation into the lipoprotein ester fractions. (orig.)

  4. Cholesterol organization in membranes at low concentrations: effects of curvature stress and membrane thickness.

    OpenAIRE

    Rukmini, R; Rawat, S S; Biswas, S. C.; Chattopadhyay, A

    2001-01-01

    Cholesterol is often found distributed nonrandomly in domains in biological and model membranes and has been reported to be distributed heterogeneously among various intracellular membranes. Although a large body of literature exists on the organization of cholesterol in plasma membranes or membranes with high cholesterol content, very little is known about organization of cholesterol in membranes containing low amounts of cholesterol. Using a fluorescent cholesterol analog (25-[N-[(7-nitrobe...

  5. Serum albumin acts as a shuttle to enhance cholesterol efflux from cells[S

    OpenAIRE

    Sankaranarayanan, Sandhya; de la Llera-Moya, Margarita; Drazul-Schrader, Denise; Phillips, Michael C.; Kellner-Weibel, Ginny; Rothblat, George H.

    2013-01-01

    An important mechanism contributing to cell cholesterol efflux is aqueous transfer in which cholesterol diffuses from cells into the aqueous phase and becomes incorporated into an acceptor particle. Some compounds can enhance diffusion by acting as shuttles transferring cholesterol to cholesterol acceptors, which act as cholesterol sinks. We have examined whether particles in serum can enhance cholesterol efflux by acting as shuttles. This task was accomplished by incubating radiolabeled J774...

  6. Dietary Cholesterol Affects Plasma Lipid Levels, the Intravascular Processing of Lipoproteins and Reverse Cholesterol Transport without Increasing the Risk for Heart Disease

    Directory of Open Access Journals (Sweden)

    Jacqueline Barona

    2012-08-01

    Full Text Available The associations between dietary cholesterol and heart disease are highly controversial. While epidemiological studies and clinical interventions have shown the lack of correlation between cholesterol intake and cardiovascular disease (CVD risk, there is still concern among health practitioners and the general population regarding dietary cholesterol. In this review, several clinical studies utilizing cholesterol challenges are analyzed in terms of changes that occur in lipoprotein metabolism resulting from excess consumption of cholesterol. Dietary cholesterol has been shown to increase both LDL and HDL in those individuals who respond to a cholesterol challenge without altering the LDL cholesterol/HDL cholesterol ratio, a key marker of CVD risk. Further, dietary cholesterol has been shown to increase only HDL with no changes in LDL with average cholesterol consumption and during weight loss interventions. Ingestion of cholesterol has also been shown to increase the size of both LDL and HDL particles with the associated implications of a less atherogenic LDL particle as well as more functional HDL in reverse cholesterol transport. Other changes observed in lipoprotein metabolism are a greater number of large LDL and decreases in small LDL subfractions. All this information put together points to specific roles of dietary cholesterol in substantially altering intravascular processing of lipoproteins as well as reverse cholesterol transport.

  7. CHOLESTEROL LEVELS AND SUICIDAL BEHAVIOR: A CASE CONTROL STUDY

    Directory of Open Access Journals (Sweden)

    Nikhil

    2014-06-01

    Full Text Available BACKGROUND: In modern psychiatry, there is a movement to understand mental health, not solely based on behaviors and subjective report, but also based on objective markers of illness. Several studies have focused on a relationship between serum cholesterol levels and aggressive behaviors including suicide. AIM: To identify a potential link between cholesterol and suicidal behavior. MATERIAL AND METHODS: 150 patients with psychiatry diagnosis were divided into three equal groups (50 each: those who had a recent suicidal attempt, those who had suicidal ideations but no attempts and those with psychiatry diagnosis but no suicidal ideations and attempts. Blood sample for total cholesterol level was on IPD or OPD basis. The study was started after taking approval from institute ethical committee. Analysis was done using Chi square test. OBSERVATIONS AND RESULTS: It was found that maximum patients who attempted suicide belonged to major depression and schizophrenia followed by substance dependence and bipolar affective disorder (BPAD with major depression and there was statistical difference in cholesterol levels of patients with suicide attempt, with suicidal ideations and control group. 42% and 44% of major depression and schizophrenia cases respectively had low total serum cholesterol levels (below 160 mg%. CONCLUSION: There is a potential link between serum total cholesterol levels and suicidal behavior. Taking the literature as a whole there is substantial evidence that low cholesterol levels are found in suicidal behaviors of various psychiatric illnesses especially major depressive disorder, schizophrenia, substance dependence and bipolar depressive disorder

  8. Quantitation of cholesterol oxidation products in unirradiated and irradiated meats

    International Nuclear Information System (INIS)

    A method to detect 7-ketocholesterol, cholesterol-5β,6β-epoxide, cholesterol-5α,6α-epoxide, 4-cholesten-3-one, 4,6-cholestadien-3-one and 4-cholestene-3,6-dione in unirradiated and irradiated beef, pork and veal was developed by use of chloroform-methanol-water extraction, solid-phase extraction, column separation, thin-layer chromatography and gas chromatography. This method recovered 78–88% of the cholesterol oxidation products and detected the cholesterol oxidation products at 10 ppb or higher. Irradiation of the meats to a dose of 10 kGy increased these compounds, except 4,6-cholestadien-3-one for all three types of meat, over unirradiated, and except cholesterol-5α,6α-epoxide and 4-cholesten-3-one for the pork. All the cholesterol oxidation products in the unirradiated meats increased during storage at 0–4°C for 2 wk with some exceptions for the pork. The increases of cholesterol oxidation products in stored irradiated meats were greater than those in the unirradiated

  9. Cholesterol induces fetal rat enterocyte death in culture

    Directory of Open Access Journals (Sweden)

    Gazzola J.

    2004-01-01

    Full Text Available The effect of cholesterol on fetal rat enterocytes and IEC-6 cells (line originated from normal rat small intestine was examined. Both cells were cultured in the presence of 20 to 80 µM cholesterol for up to 72 h. Apoptosis was determined by flow cytometric analysis and fluorescence microscopy. The expression of HMG-CoA reductase and peroxisome proliferator-activated receptor gamma (PPARgamma was measured by RT-PCR. The addition of 20 µM cholesterol reduced enterocyte proliferation as early as 6 h of culture. Reduction of enterocyte proliferation by 28 and 41% was observed after 24 h of culture in the presence and absence of 10% fetal calf serum, respectively, with the effect lasting up to 72 h. Treatment of IEC-6 cells with cholesterol for 24 h raised the proportion of cells with fragmented DNA by 9.7% at 40 µM and by 20.8% at 80 µM. When the culture period was extended to 48 h, the effect of cholesterol was still more pronounced, with the percent of cells with fragmented DNA reaching 53.5% for 40 µM and 84.3% for 80 µM. Chromatin condensation of IEC-6 cells was observed after treatment with cholesterol even at 20 µM. Cholesterol did not affect HMG-CoA reductase expression. A dose-dependent increase in PPARgamma expression in fetal rat enterocytes was observed. The expression of PPAR-gamma was raised by 7- and 40-fold, in the presence and absence of fetal calf serum, respectively, with cholesterol at 80 mM. The apoptotic effect of cholesterol on enterocytes was possibly due to an increase in PPARgamma expression.

  10. Cholesterol and fat lowering with hydrophobic polysaccharide derivatives.

    Science.gov (United States)

    Čopíková, Jana; Taubner, Tomáš; Tůma, Jan; Synytsya, Andriy; Dušková, Dagmar; Marounek, Milan

    2015-02-13

    Hydrophobic derivatives of highly methylated citrus pectin, chitosan and cellulose were prepared and tested as potential cholesterol lowering agents. Elemental analysis and spectroscopic methods confirmed high substitution degree for all of them. Substitution with long alkyl/acyl groups led to significant changes in physical and thermal properties of modified polysaccharides. Sorption of cholate and cholesterol by these polysaccharide-based sorbents was estimated in comparison with the synthetic drug cholestyramine. It was found that modified polysaccharides have high affinity to cholesterol. By contrast, cholestyramine was effective only in cholate sorption. PMID:25458291

  11. Lipid-based transfection reagents can interfere with cholesterol biosynthesis.

    Science.gov (United States)

    Danielli, Mauro; Marinelli, Raúl A

    2016-02-15

    Lipid-based transfection reagents are widely used for delivery of small interfering RNA into cells. We examined whether the commonly used commercial transfection reagents DharmaFECT-4 and Lipofectamine 2000 can interfere with lipid metabolism by studying cholesterogenesis. Cholesterol de novo synthesis from [(14)C]acetate was assessed in human hepatocyte-derived Huh-7 cells. The results revealed that DharmaFECT, but not Lipofectamine, markedly inhibited cholesterol biosynthesis by approximately 70%. Cell viability was not significantly altered. These findings suggest that caution is required in the choice of certain lipid-based transfection reagents for gene silencing experiments, particularly when assessing cholesterol metabolism. PMID:26656923

  12. Reverse cholesterol transport: From classical view to new insights

    Institute of Scientific and Technical Information of China (English)

    Astrid; E; van; der; Velde

    2010-01-01

    Cholesterol is of vital importance for the human body. It is a constituent for most biological membranes, it is needed for the formation of bile salts, and it is the pre- cursor for steroid hormones and vitamin D. However, the presence of excess cholesterol in cells, and in particular in macrophages in the arterial vessel wall, might be harmful. The accumulation of cholesterol in arteries can lead to atherosclerosis, and in turn, to other cardiovascular diseases. The route that is primarily thought to be re...

  13. Does fat in milk, butter and and cholesterol differently?

    DEFF Research Database (Denmark)

    Tholstrup, T,; Høy, Carl-Erik; Andersen, L.N.;

    2004-01-01

    8 hours following intake of the meals. Results: Fasting LDL cholesterol concentration was significantly higher after butter than cheese diet (p 0.037), with a borderline significant difference in total cholesterol (p = 0.054) after the experimental periods of three weeks. Postprandial glucose showed...... a higher response after cheese diet than after milk diet (p = 0.010, diet X time interaction). Conclusions: A different effect of fat in milk and butter could not be confirmed in this study. The moderately lower LDL cholesterol after cheese diet compared to butter diet should be investigated further....

  14. Statins: Cholesterol guidelines and Indian perspective

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    Anil S Menon

    2015-01-01

    Full Text Available Statins have become an important drug in preventing the occurrence of atherosclerotic cardiovascular disease (ASCVD. The effectiveness of statins in reducing ASCVD has been established in large-scale clinical trials. The lipid management guidelines have been periodically modified due to accumulating evidence about the proportionate benefit achieved with a progressive reduction in cholesterol levels with higher doses of statins and even in those at low risk of development of ASCVD. The current American College of Cardiology/American Heart Association guidelines have based its recommendations from data gathered exclusively from randomized controlled trials. It has simplified the use of statins, but also raised questions regarding the validity of its cardiovascular event risk prediction tool. Epidemiology of cardiovascular disease in India differs from the western population; there is an increased the prevalence of metabolic syndrome and atherogenic dyslipidemia phenotype a group not addressed in the current guidelines. The guidelines are based on trials, which do not have a representative South Asian population. This article reviews the relevant literature, and examines the issues involved in adopting the guidelines to the Indian population.

  15. Assessing Cholesterol Storage in Live Cells and C. elegans by Stimulated Raman Scattering Imaging of Phenyl-Diyne Cholesterol

    Science.gov (United States)

    Lee, Hyeon Jeong; Zhang, Wandi; Zhang, Delong; Yang, Yang; Liu, Bin; Barker, Eric L.; Buhman, Kimberly K.; Slipchenko, Lyudmila V.; Dai, Mingji; Cheng, Ji-Xin

    2015-01-01

    We report a cholesterol imaging method using rationally synthesized phenyl-diyne cholesterol (PhDY-Chol) and stimulated Raman scattering (SRS) microscope. The phenyl-diyne group is biologically inert and provides a Raman scattering cross section that is 88 times larger than the endogenous C = O stretching mode. SRS microscopy offers an imaging speed that is faster than spontaneous Raman microscopy by three orders of magnitude, and a detection sensitivity of 31 μM PhDY-Chol (~1,800 molecules in the excitation volume). Inside living CHO cells, PhDY-Chol mimics the behavior of cholesterol, including membrane incorporation and esterification. In a cellular model of Niemann-Pick type C disease, PhDY-Chol reflects the lysosomal accumulation of cholesterol, and shows relocation to lipid droplets after HPβCD treatment. In live C. elegans, PhDY-Chol mimics cholesterol uptake by intestinal cells and reflects cholesterol storage. Together, our work demonstrates an enabling platform for study of cholesterol storage and trafficking in living cells and vital organisms.

  16. The origin of cholesterol in chyle demonstrated by nuclear indicator methods; Origines du cholesterol du chyle mises en evidence par la methode des indicateurs nucleaires

    Energy Technology Data Exchange (ETDEWEB)

    Vyas, M

    1962-07-01

    In order to obtain information about the mechanism of the intestinal absorption of cholesterol, rats having a lymphatic abdominal fistula are used. The animals receive either 4-{sup 14}C- cholesterol subcutaneously or orally, or the 1-{sup 14}C acetate. The study of the specific radio-activities of the cholesterol in chyle, in serum, in the lining, and in the intestinal contents makes it possible to define the roles played by the transfer cholesterol from the serum, by the cholesterol synthesised intestinally, and by the absorption cholesterol, in the formations of the lymph and of the chylomicrons. A new theory is proposed for the mechanism of cholesterol absorption. (author) [French] Pour obtenir des renseignements concernant le mecanisme de l'absorption intestinale du cholesterol, on utilise des rats porteurs d'une fistule lymphatique abdominale. Les animaux recoivent soit du cholesterol 4-{sup 14}C par voie sous-cutanee ou par voie orale, soit de l'acetate 1-{sup 14}C. L'etude des radioactivites specifiques du cholesterol du chyle, du serum, de la paroi et du contenu intestinal permet de preciser les roles joues par le cholesterol de transfert d'origine serique, par le cholesterol de synthese intestinale et par le cholesterol d'absorption, dans la formation de la lymphe et des chylomicrons. Une theorie nouvelle concernant le mecanisme de l'absorption du cholesterol est proposee. (auteur)

  17. Comparison of biosensors based on entrapment of cholesterol oxidase and cholesterol esterase in electropolymerized films of polypyrrole and diaminonaphthalene derivatives for amperometric determination of cholesterol.

    Science.gov (United States)

    Vidal, J C; Garcia-Ruiz, E; Espuelas, J; Aramendia, T; Castillo, J R

    2003-09-01

    Cholesterol amperometric biosensors constructed with enzymes entrapped in electropolymerized layers of polypyrrole and poly-naphthalene derivative polymers are compared. The biosensors are based on entrapment of cholesterol oxidase and/or cholesterol esterase in monolayer or multilayer films electrochemically synthesised from pyrrole, 1,8-diaminonaphthalene (1,8-DAN), and 1,5-diaminonaphthalene (1,5-DAN) monomers. Seven configurations were assayed and compared, and different analytical properties were obtained depending on the kind of polymer and the arrangement of the layers. The selectivity properties were evaluated for the different monolayer and bilayer configurations proposed as a function of the film permeation factor. All the steps involved in the preparation of the biosensors and determination of cholesterol were carried out in a flow system. Sensitivity and selectivity depend greatly on hydrophobicity, permeability, compactness, thickness, and the kind of the polymer used. In some cases a protective outer layer of non-conducting poly( o-phenylenediamine) polymer improves the analytical characteristics of the biosensor. A comparative study was made of the analytical performance of each of the configurations developed. The biosensors were also applied to the flow-injection determination of cholesterol in a synthetic serum. PMID:12923606

  18. Adrenal scanning with {sup 131}I-cholesterol; Diagnostik von Nebennierenrindenerkrankungen mit {sup 131}I-Cholesterol

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, K. [Klinik und Poliklinik fuer Nuklearmedizin, Klinikum der Ludwig-Maximilians-Univ. Muenchen (Germany)

    2009-03-15

    Adrenal scanning with {sup 131}I-19-cholesterol is used in patients with various forms of adrenal malfunction (adreno-cortical carcinoma or adenoma, hypothalamic-hypophyseal form of Cushing's syndrome, adrenal hirsutism, primary or secondary adrenocortical insufficiency). Adrenal scanning is optimal between the fourth and tenth day after intravenous injection of {sup 131}I-19-cholesterol. This method makes it possible to estimate the size and functional status of the adrenals. Limitation of the method is the relatively high radiation dose of {sup 131}I-19-cholesterol. (orig.)

  19. Cholesterol granuloma of the orbit: An atypical presentation

    Directory of Open Access Journals (Sweden)

    Syed A R Rizvi

    2014-01-01

    Full Text Available Cholesterol granuloma is a rare, well-defined lesion of the orbit. In the orbit, diploe of the frontal bone is involved almost exclusively. We report an atypical case of cholesterol granuloma involving superomedial quadrant of orbit. A 42-year-old male presented with progressive, painless, proptosis with infero-temporal displacement of left eye. A large mass was felt beneath the bony orbital margin in the superomedial quadrant of the left orbit. Computerized tomography (CT scan revealed an extraconal superomedial, heterogeneous enhancing mass which was isodense with brain and pushing the globe inferolaterally and anteriorly. Excision biopsy of the tumor revealed the typical features of a cholesterol granuloma without any epithelial elements. Cholesterol granuloma of the orbit is a rare entity, but it can be diagnosed and differentiated from other lesions of the superior orbit by its characteristic clinical, radiological and histopathological features. An appropriate intervention in time carries a good prognosis with almost no recurrence.

  20. Alternative to decrease cholesterol in sheep milk cheeses.

    Science.gov (United States)

    Gómez-Cortés, P; Viturro, E; Juárez, M; de la Fuente, M A

    2015-12-01

    The presence of cholesterol in foods is of nutritional interest because high levels of this molecule in human plasma are associated with an increasing risk of cardiovascular disease and nowadays consumers are demanding healthier products. The goal of this experiment was to diminish the cholesterol content of Manchego, the most popular Spanish cheese manufactured from ewes milk. For this purpose three bulk milks coming from dairy ewe fed with 0 (Control), 3 and 6% of linseed supplement on their diet were used. Nine cheeses (3 per bulk milk) were manufactured and ripened for 3 months. Cholesterol of ewes milk cheese from 6% to 12% linseed supplemented diets decreased by 9.6% and 16.1% respectively, therefore supplying a healthier profile. In a second experiment, different sources of unsaturated fatty acids (rich in oleic, linoleic and α-linolenic acids) were supplemented to dairy ewes and no significant differences were found on cheese cholesterol levels. PMID:26041199

  1. Three cases of cholesterol granuloma in the mandible

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Min Jung; Huh, Kyung Hoe; Yi, Won Jin; Moon, Je Woon; Choi, Soon Chul [Seoul National Univ. School of Dentitry, Seoul (Korea, Republic of); Shin, Jae Myung [Inje Univ. College of Medicine, Kimhae (Korea, Republic of)

    2007-12-15

    Cholesterol granuloma is an unusual clinical entity described as an inflammatory granulation in response to the deposit of cholesterol crystals. It can develop in any portion of air cells within the temporal bone as a result of a lack of aeration and inadequate drainage, especially in the middle ear cavity. Here, we report very unusual three cases of cholesterol granuloma developed in mandible. In the first case a 68-year-old male with a large mass arising from the mandible was observed. Panoramic radiograph and computed tomography scans revealed a huge expanding lesion in the mandible. In the second case a 47-years-old female with a cystic lesion in the mandible was observed. And in the third case a 19-year-old male complaining atypical facial pain had a large lesion in the mandibular ramous. The histopathologic examinations of the cases showed numerous cholesterol crystal surrounded by multinucleated foreign body giant cells.

  2. Helical synthetic peptides that stimulate cellular cholesterol efflux

    Science.gov (United States)

    Bielicki, John K.; Natarajan, Pradeep

    2010-04-06

    The present invention provides peptides comprising at least one amphipathic alpha helix and having an cholesterol mediating activity and a ABCA stabilization activity. The invention further provides methods of using such peptides.

  3. Preterm delivery and low maternal serum cholesterol level: any correlation?

    Directory of Open Access Journals (Sweden)

    Ayodeji A. Oluwole

    2014-04-01

    Results: The study showed an incidence of 5.0% for preterm delivery in the low risk study patients. Preterm birth was 4.83-times more common with low total maternal cholesterol than with midrange total cholesterol (11.8% versus 2.2%, P = 0.024. Conclusions: We can infer from the study that the low maternal serum cholesterol (hypocholesterolaemia is associated with preterm delivery. We can therefore recommend on this basis that the concept of an optimal range for maternal serum cholesterol during pregnancy may have merit and pregnant women should be encouraged to follow a healthy, balanced diet and ensure regular antenatal visit to their healthcare provider. [Int J Reprod Contracept Obstet Gynecol 2014; 3(2.000: 442-446

  4. Interaction between cholesterol and chitosan in Langmuir monolayers

    Directory of Open Access Journals (Sweden)

    Felippe J. Pavinatto

    2005-06-01

    Full Text Available Chitosan incorporated in the aqueous subphase is found to affect the Langmuir monolayers of cholesterol, causing the surface pressure and the surface potential isotherms to become more expanded. The mean molecular area per cholesterol molecule in the condensed monolayer increases from 53 Ų in the absence of chitosan to 61 Ų for a concentration of 0.100 mg/mL of chitosan in the subphase. If additional chitosan is incorporated in the subphase, no change is noted, which points to saturation in the effects from chitosan. The interaction between chitosan and cholesterol probably occurs via hydrogen bonding. The monolayer expansion is also manifested in the monolayer morphology, as indicated by Brewster angle microscopy measurements, where larger cholesterol domains are visualized when chitosan is present in the subphase.

  5. Genetic High-Cholesterol Condition More Common Than Thought

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_157755.html Genetic High-Cholesterol Condition More Common Than Thought Researchers ... the United States, she said. Rates of the genetic disorder vary based on racial/ethnic background, but ...

  6. Cholesterol-Lowering Probiotics as Potential Biotherapeutics for Metabolic Diseases

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    2012-01-01

    Full Text Available Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels and the risks of coronary heart disease. Current dietary strategies for the prevention of cardiovascular disease advocate adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in experimental conditions, low-fat diets offer an effective means of reducing blood cholesterol concentrations on a population basis, these appear to be less effective, largely due to poor compliance, attributed to low palatability and acceptability of these diets to the consumers. Due to the low consumer compliance, attempts have been made to identify other dietary components that can reduce blood cholesterol levels. Supplementation of diet with fermented dairy products or lactic acid bacteria containing dairy products has shown the potential to reduce serum cholesterol levels. Various approaches have been used to alleviate this issue, including the use of probiotics, especially Bifidobacterium spp. and Lactobacillus spp.. Probiotics, the living microorganisms that confer health benefits on the host when administered in adequate amounts, have received much attention on their proclaimed health benefits which include improvement in lactose intolerance, increase in natural resistance to infectious disease in gastrointestinal tract, suppression of cancer, antidiabetic, reduction in serum cholesterol level, and improved digestion. In addition, there are numerous reports on cholesterol removal ability of probiotics and their hypocholesterolemic effects. Several possible mechanisms for cholesterol removal by probiotics are assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface

  7. Cholesterol Check (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2015-09-10

    Heart disease and stroke are among the leading causes of death in the U.S. One of the main risk factors is high blood cholesterol. In this podcast, Dr. Carla Mercado discusses the importance of a healthy diet and regular screening to prevent high blood cholesterol.  Created: 9/10/2015 by MMWR.   Date Released: 9/10/2015.

  8. Dietary fat, cholesterol and colorectal cancer in a prospective study

    OpenAIRE

    Järvinen, R.; Knekt, P; Hakulinen, T; Rissanen, H; Heliövaara, M

    2001-01-01

    The relationships between consumption of total fat, major dietary fatty acids, cholesterol, consumption of meat and eggs, and the incidence of colorectal cancers were studied in a cohort based on the Finnish Mobile Clinic Health Examination Survey. Baseline (1967–1972) information on habitual food consumption over the preceding year was collected from 9959 men and women free of diagnosed cancer. A total of 109 new colorectal cancer cases were ascertained late 1999. High cholesterol intake was...

  9. Reverse cholesterol transport: a potential therapeutic target for atherosclerosis

    OpenAIRE

    Ying ZHAO

    2011-01-01

    Atherosclerosis is the major cause of death in the Western society due to the development of acute clinical events such as myocardial infarction and cerebral stroke. Currently, lowering plasma LDL cholesterol (LDL-C) levels using statins, inhibitors of de-novo cholesterol synthesis, is the main therapeutic strategy to prevent the progression of atherosclerosis. The remaining high incidence of cardiovascular disease indicates a clear need for new therapies. Numerous epidemiological studies hav...

  10. Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Xin-ting WANG; Jia LI; Li LIU; Nan HU; Shi JIN; Can LIU; Dan MEI; Xiao-dong LIU

    2012-01-01

    Aim:Diabetes is associated with elevated serum total cholesterol level and disrupted lipoprotein subfractions.The aim of this study was to examine alterations in the tissue cholesterol contents closely related to diabetic complications.Methods:Intraperitoneal injection of streptozotocin was used to induce type 1 diabetes in adult male Sprague-Dawley rats.On d 35 after the injection,liver,heart,intestine,kidney,pancreas,cerebral cortex and hippocampus were isolated from the rats.The content of total and free cholesterol in the tissues was determined using HPLC.The ATP-binding cassette protein A1 (ABCA1) protein and ApoE mRNA were measured using Western blot and QT-PCR analyses,respectively.Results:In diabetic rats,the level of free cholesterol was significantly decreased in the peripheral tissues,but significantly elevated in hippocampus,as compared with those in the control rats.Diabetic rats showed a trend of decreasing the total cholesterol level in the peripheral tissues,but significant change was only found in kidney and liver.In diabetic rats,the level of the ABCA1 protein was significantly increased in the peripheral tissues and cerebral cortex; the expression of ApoE mRNA was slightly decreased in hippocampus and cerebral cortex,but the change had no statistical significance.Conclusion:Type 1 diabetes decreases the free cholesterol content in the peripheral tissues and increases the free cholesterol content in hippocampus.The decreased free cholesterol level in the peripheral tissues may be partly due to the increased expression of the ABCA1 protein.

  11. Cholesterol oxidase: sources, physical properties and analytical applications.

    Science.gov (United States)

    MacLachlan, J; Wotherspoon, A T; Ansell, R O; Brooks, C J

    2000-04-01

    Since Flegg (H.M. Flegg, An investigation of the determination of serum cholesterol by an enzymatic method, Ann. Clin. Biochem. 10 (1973) 79-84) and Richmond (W. Richmond, The development of an enzymatic technique for the assay of cholesterol in biological fluids, Scand. J. clin. Lab. Invest. 29 (1972) 25; W. Richmond, Preparation and properties of a bacterial cholesterol oxidase from Nocardia sp. and its application to enzyme assay of total cholesterol in serum, Clinical Chemistry 19 (1973) 1350-1356) first illustrated the suitability of cholesterol oxidase (COD) for the analysis of serum cholesterol, COD has risen to become the most widely used enzyme in clinical laboratories with the exception of glucose oxidase (GOD). The use is widespread because assays incorporating the enzyme are extremely simple, specific, and highly sensitive and thus offer distinct advantages over the Liebermann-Burchard analytical methodologies which employ corrosive reagents and can be prone to unreliable results due to interfering substances such as bilirubin. Individuals can now readily determine their own serum cholesterol levels with a simple disposable test kit. This review discusses COD in some detail and includes the topics: (1) The variety of bacterial sources available; (2) The various extraction/purification protocols utilised in order to obtain protein of sufficient clarification (purity) for use in food/clinical analysis; (3) Significant differences in the properties of the individual enzymes; (4) Substrate specificities of the various enzymes; (5) Examples of biological assays which have employed cholesterol oxidase as an integral part of the analysis, and the various assay protocols; (6) New steroidal products of COD. This review is not a comprehensive description of published work, but is intended to provide an account of recent and current research, and should promote further interest in the application of enzymes to analytical selectivity. PMID:10822008

  12. Optimizing Conditions to Cholesterol Adsorbed with Carboxymethyl Chitosan

    OpenAIRE

    Mardiyah Kurniasih; Dwi Kartika; Riyanti Riyanti

    2016-01-01

    A research on optimizing conditions to cholesterol adsorbed have been performed. Optimization was performed by varying: contact time, adsorbent weight and temperature of the system's. A full factorial experimental design was used in this study. Characterization performed on the synthesized chitosan and carboxymethyl chitosan including FTIR, water content, ash content, solubility, porosity, and swelling effect. The results showed that carboxymethyl chitosan able to adsorb cholesterol under con...

  13. Cholesterol depletion disorganizes oocyte membrane rafts altering mouse fertilization.

    Directory of Open Access Journals (Sweden)

    Jorgelina Buschiazzo

    Full Text Available Drastic membrane reorganization occurs when mammalian sperm binds to and fuses with the oocyte membrane. Two oocyte protein families are essential for fertilization, tetraspanins and glycosylphosphatidylinositol-anchored proteins. The firsts are associated to tetraspanin-enriched microdomains and the seconds to lipid rafts. Here we report membrane raft involvement in mouse fertilization assessed by cholesterol modulation using methyl-β-cyclodextrin. Cholesterol removal induced: (1 a decrease of the fertilization rate and index; and (2 a delay in the extrusion of the second polar body. Cholesterol repletion recovered the fertilization ability of cholesterol-depleted oocytes, indicating reversibility of these effects. In vivo time-lapse analyses using fluorescent cholesterol permitted to identify the time-point at which the probe is mainly located at the plasma membrane enabling the estimation of the extent of the cholesterol depletion. We confirmed that the mouse oocyte is rich in rafts according to the presence of the raft marker lipid, ganglioside GM1 on the membrane of living oocytes and we identified the coexistence of two types of microdomains, planar rafts and caveolae-like structures, by terms of two differential rafts markers, flotillin-2 and caveolin-1, respectively. Moreover, this is the first report that shows characteristic caveolae-like invaginations in the mouse oocyte identified by electron microscopy. Raft disruption by cholesterol depletion disturbed the subcellular localization of the signal molecule c-Src and the inhibition of Src kinase proteins prevented second polar body extrusion, consistent with a role of Src-related kinases in fertilization via signaling complexes. Our data highlight the functional importance of intact membrane rafts for mouse fertilization and its dependence on cholesterol.

  14. HIV-Cholesterol Connection Suggests a New Antiretroviral Strategy

    OpenAIRE

    Zahedi Mujawar; Honor Rose; Morrow, Matthew P.; Tatiana Pushkarsky; Larisa Dubrovsky; Nigora Mukhamedova; Ying Fu; Anthony Dart; Orenstein, Jan M.; Bobryshev, Yuri V.; Michael Bukrinsky; Dmitri Sviridov

    2006-01-01

    Several steps of HIV-1 replication critically depend on cholesterol. HIV infection is associated with profound changes in lipid and lipoprotein metabolism and an increased risk of coronary artery disease. Whereas numerous studies have investigated the role of anti-HIV drugs in lipodystrophy and dyslipidemia, the effects of HIV infection on cellular cholesterol metabolism remain uncharacterized. Here, we demonstrate that HIV-1 impairs ATP-binding cassette transporter A1 (ABCA1)-dependent chole...

  15. Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

    DEFF Research Database (Denmark)

    Elsøe, Sara; Christoffersen, Christina; Luchoomun, Jayraz;

    2013-01-01

    The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice.......The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice....

  16. Cholesterol granuloma of the right epididymis mimicking an acute scrotum

    Institute of Scientific and Technical Information of China (English)

    Borislav Spajic; Hrvoje Cupic; Goran Stimac; Ivica Brigic; Bozo Kruslin; Ognjen Kraus

    2006-01-01

    @@ Dear Sir, I am B. Spajic, the urologist from Clinical Department of Urology, Sestre Milosrdnice University Hospital,Zagreb, Croatia. Recently, we had a rare case of a cholesterol granuloma of the right epididymis at our department, showing clinical signs of acute scrotum. The case described here appears to be the second reporting cholesterol granuloma in the epididymis and the first one presenting with clinical signs of acute scrotum.

  17. Elastic deformation and failure of lipid bilayer membranes containing cholesterol.

    OpenAIRE

    Needham, D; Nunn, R. S.

    1990-01-01

    Giant bilayer vesicles were reconstituted from several lipids and lipid/cholesterol (CHOL) mixtures: stearolyloleoylphosphatidylcholine (SOPC), bovine sphingomyelin (BSM), diarachidonylphosphatidylcholine (DAPC), SOPC/CHOL, BSM/CHOL, DAPC/CHOL, and extracted red blood cell (RBC) lipids with native cholesterol. Single-walled vesicles were manipulated by micropipette suction and several membrane material properties were determined. The properties measured were the elastic area compressibility m...

  18. Emerging Roles for Cholesterol and Lipoproteins in Lung Disease

    OpenAIRE

    Gowdy, Kymberly M; Fessler, Michael B.

    2012-01-01

    Dyslipidemia, the condition of elevated serum triglycerides, elevated low-density lipoprotein cholesterol, and/or low high-density lipoprotein cholesterol, is a public health problem of growing concern. Dyslipidemia clusters with other disorders of the metabolic syndrome that together influence, and may derive from, chronic inflammation. While best recognized as a risk factor for atherosclerotic cardiovascular disease, lipid dysregulation has recently been shown to influence a variety of dise...

  19. The Role of Cholesterol in Driving IAPP-Membrane Interactions.

    Science.gov (United States)

    Sciacca, Michele F M; Lolicato, Fabio; Di Mauro, Giacomo; Milardi, Danilo; D'Urso, Luisa; Satriano, Cristina; Ramamoorthy, Ayyalusamy; La Rosa, Carmelo

    2016-07-12

    Our knowledge of the molecular events underlying type 2 diabetes mellitus-a protein conformational disease characterized by the aggregation of islet amyloid polypeptide (IAPP) in pancreatic β cells-is limited. However, amyloid-mediated membrane damage is known to play a key role in IAPP cytotoxicity, and therefore the effects of lipid composition on modulating IAPP-membrane interactions have been the focus of intense research. In particular, membrane cholesterol content varies with aging and consequently with adverse environmental factors such as diet and lifestyle, but its role in the development of the disease is controversial. In this study, we employ a combination of experimental techniques and in silico molecular simulations to shed light on the role of cholesterol in IAPP aggregation and the related membrane disruption. We show that if anionic POPC/POPS vesicles are used as model membranes, cholesterol has a negligible effect on the kinetics of IAPP fibril growth on the surface of the bilayer. In addition, cholesterol inhibits membrane damage by amyloid-induced poration on membranes, but enhances leakage through fiber growth on the membrane surface. Conversely, if 1:2 DOPC/DPPC raft-like model membranes are used, cholesterol accelerates fiber growth. Next, it enhances pore formation and suppresses fiber growth on the membrane surface, leading to leakage. Our results highlight a twofold effect of cholesterol on the amyloidogenicity of IAPP and help explain its debated role in type 2 diabetes mellitus. PMID:27410742

  20. Anaerobic oxidation of cholesterol by a denitrifying enrichment.

    Science.gov (United States)

    Barrandeguy, E; Tarlera, S

    2001-01-01

    Sterols (e.g. cholesterol) present in wool scouring effluent represent the most recalcitrant fraction in anaerobic treatment. This study was conducted to examine the feasibility of removal of this organic load through a denitrifying post-treatment stage. A stable cholesterol-denitrifying enrichment (CHOL-1) was obtained from sludge of a bench-scale upflow sludge bed (USB) denitrifying reactor integrated to a carbon and nitrogen removal system for sanitary landfill leachate. According to the amounts of cholesterol degraded and of nitrite and nitrogen gas formed, the capacity for complete cholesterol oxidation under anaerobic conditions by CHOL-1 can be assumed. Nitrite accumulation observed at a low C/N ratio outlines the importance of determining the optimal C/N ratio for adequate denitrifying reactor performance. The enrichment was partly identified with molecular analysis of cloned 16S rDNA sequences revealing the presence of two groups of bacteria belonging to the beta subclass of the Proteobacteria. According to analysis of sequences, it can be inferred that a yet uncultivated new bacterium is the one responsible for cholesterol oxidation. Results of this study suggest that sludge from a denitrifying reactor treating leachate is potentially useful in a combined anaerobic-anoxic system for degradation of cholesterol that remains after methanogenic treatment. PMID:11575077

  1. Cholesterol-dependent hemolytic activity of Passiflora quadrangularis leaves

    Directory of Open Access Journals (Sweden)

    L.N. Yuldasheva

    2005-07-01

    Full Text Available Plants used in traditional medicine are rich sources of hemolysins and cytolysins, which are potential bactericidal and anticancer drugs. The present study demonstrates for the first time the presence of a hemolysin in the leaves of Passiflora quadrangularis L. This hemolysin is heat stable, resistant to trypsin treatment, has the capacity to froth, and acts very rapidly. The hemolysin activity is dose-dependent, with a slope greater than 1 in a double-logarithmic plot. Polyethylene glycols of high molecular weight were able to reduce the rate of hemolysis, while liposomes containing cholesterol completely inhibited it. In contrast, liposomes containing phosphatidylcholine were ineffective. The Passiflora hemolysin markedly increased the conductance of planar lipid bilayers containing cholesterol but was ineffective in cholesterol-free bilayers. Successive extraction of the crude hemolysin with n-hexane, chloroform, ethyl acetate, and n-butanol resulted in a 10-fold purification, with the hemolytic activity being recovered in the n-butanol fraction. The data suggest that membrane cholesterol is the primary target for this hemolysin and that several hemolysin molecules form a large transmembrane water pore. The properties of the Passiflora hemolysin, such as its frothing ability, positive color reaction with vanillin, selective extraction with n-butanol, HPLC profile, cholesterol-dependent membrane susceptibility, formation of a stable complex with cholesterol, and rapid erythrocyte lysis kinetics indicate that it is probably a saponin.

  2. Effect of Moderate Alcohol Consumption on Parameters of Reverse Cholesterol Transport in Postmenopausal Women

    NARCIS (Netherlands)

    Sierksma, A.; Vermunt, S.H.F.; Lankhuizen, I.M.; Gaag, M.S. van der; Scheek, L.M.; Grobbee, D.E.; Tol, A. van; Hendriks, H.F.J.

    2004-01-01

    Background: Alcohol consumption is associated with increased high-density lipoprotein (HDL) cholesterol levels. One of the main antiatherogenic functions of HDL is reverse cholesterol transport. Three early steps of reverse cholesterol transport are (1) cellular cholesterol efflux, (2) plasma choles

  3. Trans-intestinal cholesterol effl ux is not mediated through high density lipoprotein

    NARCIS (Netherlands)

    Vrins, C.L.; Ottenhoff, R.; Oever, K. van den; Waart, D.R. de; Kruyt, J.K.; Zhao, Y.; Berkel, T.J. van; Havekes, L.M.; Aerts, J.M.; Eck, M. van; Rensen, P.C.; Groen, A.K.

    2012-01-01

    Transintestinal cholesterol efflux (TICE) provides an attractive target to increase body cholesterol excretion. At present, the cholesterol donor responsible for direct delivery of plasma cholesterol to the intestine is unknown. In this study, we investigated the role of HDL in TICE. ATP-binding cas

  4. LCAT, HDL Cholesterol and Ischemic Cardiovascular Disease: A Mendelian Randomization Study of HDL Cholesterol in 54,500 Individuals

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Ali Qayyum, Abbas;

    2012-01-01

    Background:Epidemiologically, high-density lipoprotein (HDL) cholesterol levels associate inversely with risk of ischemic cardiovascular disease. Whether this is a causal relation is unclear.Methods:We studied 10,281 participants in the Copenhagen City Heart Study (CCHS) and 50,523 participants in...... the Copenhagen General Population Study (CGPS), of which 991 and 1,693 participants, respectively, had developed myocardial infarction (MI) by August 2010. Participants in the CCHS were genotyped for all six variants identified by resequencing lecithin-cholesterol acyltransferase in 380 individuals....... One variant, S208T (rs4986970, allele frequency 4%), associated with HDL cholesterol levels in both the CCHS and the CGPS was used to study causality of HDL cholesterol using instrumental variable analysis.Results:Epidemiologically, in the CCHS, a 13% (0.21 mmol/liter) decrease in plasma HDL...

  5. Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus : Relevance for non-HDL cholesterol and apolipoprotein B guideline targets

    NARCIS (Netherlands)

    Kappelle, Paul J. W. H.; Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.

    2010-01-01

    The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein

  6. Effects of lovastatin and dietary cholesterol on sterol homeostasis in healthy human subjects.

    OpenAIRE

    Duane, W C

    1993-01-01

    We measured biliary and fecal sterol outputs in 12 human subjects on a metabolic ward in four randomly allocated, 6-7 wk periods: (a) lovastatin (40 mg b.i.d.) + low cholesterol diet (mean 246 mg/d), (b) lovastatin + high cholesterol diet (mean 1,071 mg/d), (c) low cholesterol diet alone, (d) high cholesterol diet alone. In addition to lowering serum LDL cholesterol, lovastatin significantly lowered biliary secretion of cholesterol, fecal output of endogenous neutral sterols, cholesterol bala...

  7. The origin of cholesterol in chyle demonstrated by nuclear indicator methods

    International Nuclear Information System (INIS)

    In order to obtain information about the mechanism of the intestinal absorption of cholesterol, rats having a lymphatic abdominal fistula are used. The animals receive either 4-14C- cholesterol subcutaneously or orally, or the 1-14C acetate. The study of the specific radio-activities of the cholesterol in chyle, in serum, in the lining, and in the intestinal contents makes it possible to define the roles played by the transfer cholesterol from the serum, by the cholesterol synthesised intestinally, and by the absorption cholesterol, in the formations of the lymph and of the chylomicrons. A new theory is proposed for the mechanism of cholesterol absorption. (author)

  8. How cholesterol interacts with membrane proteins: an exploration of cholesterol-binding sites including CRAC, CARC, and tilted domains

    OpenAIRE

    Fantini, Jacques; Barrantes, Francisco J.

    2013-01-01

    The plasma membrane of eukaryotic cells contains several types of lipids displaying high biochemical variability in both their apolar moiety (e.g., the acyl chain of glycerolipids) and their polar head (e.g., the sugar structure of glycosphingolipids). Among these lipids, cholesterol is unique because its biochemical variability is almost exclusively restricted to the oxidation of its polar −OH group. Although generally considered the most rigid membrane lipid, cholesterol can adopt a broad r...

  9. Lecithin:Cholesterol Acyltransferase (LCAT) Deficiency Promotes Differentiation of Satellite Cells to Brown Adipocytes in a Cholesterol-dependent Manner.

    Science.gov (United States)

    Nesan, Dinushan; Tavallaee, Ghazaleh; Koh, Deborah; Bashiri, Amir; Abdin, Rawand; Ng, Dominic S

    2015-12-18

    Our laboratory previously reported that lecithin:cholesterol acyltransferase (LCAT) and LDL receptor double knock-out mice (Ldlr(-/-)xLcat(-/-) or DKO) spontaneously develop functioning ectopic brown adipose tissue (BAT) in skeletal muscle, putatively contributing to protection from the diet-induced obesity phenotype. Here we further investigated their developmental origin and the mechanistic role of LCAT deficiency. Gene profiling of skeletal muscle in DKO newborns and adults revealed a classical lineage. Primary quiescent satellite cells (SC) from chow-fed DKO mice, not in Ldlr(-/-)xLcat(+/+) single-knock-out (SKO) or C57BL/6 wild type, were found to (i) express exclusively classical BAT-selective genes, (ii) be primed to express key functional BAT genes, and (iii) exhibit markedly increased ex vivo adipogenic differentiation into brown adipocytes. This gene priming effect was abrogated upon feeding the mice a 2% high cholesterol diet in association with accumulation of excess intracellular cholesterol. Ex vivo cholesterol loading of chow-fed DKO SC recapitulated the effect, indicating that cellular cholesterol is a key regulator of SC-to-BAT differentiation. Comparing adipogenicity of Ldlr(+/+)xLcat(-/-) (LCAT-KO) SC with DKO SC identified a role for LCAT deficiency in priming SC to express BAT genes. Additionally, we found that reduced cellular cholesterol is important for adipogenic differentiation, evidenced by increased induction of adipogenesis in cholesterol-depleted SC from both LCAT-KO and SKO mice. Taken together, we conclude that ectopic BAT in DKO mice is classical in origin, and its development begins in utero. We further showed complementary roles of LCAT deficiency and cellular cholesterol reduction in the SC-to-BAT adipogenesis. PMID:26494623

  10. Hydrophobic ionic liquid immoblizing cholesterol oxidase on the electrodeposited Prussian blue on glassy carbon electrode for detection of cholesterol

    International Nuclear Information System (INIS)

    A novel cholesterol biosensor was fabricated on hydrophobic ionic liquid (IL)/aqueous solution interface. The hydrophobic IL thin film played a signal amplification role because it not only enriched the cholesterol from the aqueous solution, but also immobilized matrix for cholesterol oxidase (ChOx). Prussian blue (PB) as advanced sensing materials was used as effective low-potential electron transfer mediation toward hydrogen peroxide (H2O2). The fabricated IL-ChOx/PB/Glassy carbon electrode (GCE) was characterized by electrochemical impedance spectroscopy (EIS) and cyclic voltammogram (CV), respectively. And it exhibited a linear response to cholesterol in the range of 0.01–0.40 mM with a detection limit of 4.4 μM. In addition, the kinetics behavior of cholesterol at IL-Chox/PB/GCE electrode was examined, and the electrocatalytic mechanism was proposed as shown in first scheme. ChOx immobilized in hydrophobic IL thin film was used as the first electrocatalyst for the cholesterol into H2O2, and the PB film onto the GCE was used as the second electrocatalyst for the 2e− reduction of the produced H2O2 into H2O

  11. Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo

    OpenAIRE

    Sacks, Frank M.; Rudel, Lawrence L.; Conner, Adam; Akeefe, Hassibullah; Kostner, Gerhard; Baki, Talal; Rothblat, George; de la Llera-Moya, Margarita; Asztalos, Bela; Perlman, Timothy; Zheng, Chunyu; Alaupovic, Petar; Maltais, Jo-Ann B.; Brewer, H. Bryan

    2009-01-01

    Uptake of cholesterol from peripheral cells by nascent small HDL circulating in plasma is necessary to prevent atherosclerosis. This process, termed reverse cholesterol transport, produces larger cholesterol-rich HDL that transfers its cholesterol to the liver facilitating excretion. Most HDL in plasma is cholesterol-rich. We demonstrate that treating plasma with a novel selective delipidation procedure converts large to small HDL [HDL-selectively delipidated (HDL-sdl)]. HDL-sdl contains seve...

  12. Lack of Cholesterol Awareness among Physicians Who Smoke

    Directory of Open Access Journals (Sweden)

    Richard E. Scranton

    2009-02-01

    Full Text Available Cigarette use is a known risk factor for the development of coronary artery disease (CAD as it adversely affects HDL cholesterol levels and promotes thrombogenesis. Smoking may also be associated with behavioral characteristics that potentiate the risk of CAD. A lack of cholesterol knowledge would indicate an aversion to a prevention-oriented lifestyle. Thus, our goal was to determine the association between tobacco use and knowledge of self-reported cholesterol among male physicians. Using the 1982 and follow-up questionnaires from the physician health study, we report the changes in the frequencies of awareness of self-reported total cholesterol and cardiovascular risk factors among the 22,067 participants. We classified physicians as being aware of their cholesterol if they reported a cholesterol level and unaware if the question was left unanswered. In 1997, 207 physicians were excluded, as the recorded cholesterol was not interpretable, leaving 21,860 for our follow up analyses. Using unadjusted logistic models, we determined the odds ratios (OR and 95% confidence intervals (CI of not reporting a cholesterol level in either 1982 or 1997 for each specified risk factor. We then evaluated whether the lack of cholesterol awareness at both time points was associated with the use of tobacco throughout the study. After 14-years of follow up, cholesterol awareness increased from 35.9 to 58.6 percent. During this period, the frequency of hypertension and hyperlipidemia treatment increased (13.5 to 40.5% and 0.57% to 19.6% respectively, as did the diagnosis of diabetes (2.40 to 7.79%. Behavioral characteristics such as a sedentary lifestyle and obesity also increased (27.8 to 42% and 43.5 to 53.5%, respectively, however the proportion of current smokers deceased from 11.1 to 4.05%. The percentages of individuals being unaware of their cholesterol decreased in all risk factor groups. However, individuals were likely to be unaware of their cholesterol

  13. Monomethylarsonous acid inhibited endogenous cholesterol biosynthesis in human skin fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Lei [Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521-0403 (United States); Xiao, Yongsheng [Department of Chemistry, University of California, Riverside, CA 92521-0403 (United States); Wang, Yinsheng, E-mail: yinsheng.wang@ucr.edu [Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521-0403 (United States); Department of Chemistry, University of California, Riverside, CA 92521-0403 (United States)

    2014-05-15

    Human exposure to arsenic in drinking water is a widespread public health concern, and such exposure is known to be associated with many human diseases. The detailed molecular mechanisms about how arsenic species contribute to the adverse human health effects, however, remain incompletely understood. Monomethylarsonous acid [MMA(III)] is a highly toxic and stable metabolite of inorganic arsenic. To exploit the mechanisms through which MMA(III) exerts its cytotoxic effect, we adopted a quantitative proteomic approach, by coupling stable isotope labeling by amino acids in cell culture (SILAC) with LC-MS/MS analysis, to examine the variation in the entire proteome of GM00637 human skin fibroblasts following acute MMA(III) exposure. Among the ∼ 6500 unique proteins quantified, ∼ 300 displayed significant changes in expression after exposure with 2 μM MMA(III) for 24 h. Subsequent analysis revealed the perturbation of de novo cholesterol biosynthesis, selenoprotein synthesis and Nrf2 pathways evoked by MMA(III) exposure. Particularly, MMA(III) treatment resulted in considerable down-regulation of several enzymes involved in cholesterol biosynthesis. In addition, real-time PCR analysis showed reduced mRNA levels of select genes in this pathway. Furthermore, MMA(III) exposure contributed to a distinct decline in cellular cholesterol content and significant growth inhibition of multiple cell lines, both of which could be restored by supplementation of cholesterol to the culture media. Collectively, the present study demonstrated that the cytotoxicity of MMA(III) may arise, at least in part, from the down-regulation of cholesterol biosynthesis enzymes and the resultant decrease of cellular cholesterol content. - Highlights: • MMA(III)-induced perturbation of the entire proteome of GM00637 cells is studied. • Quantitative proteomic approach revealed alterations of multiple cellular pathways. • MMA(III) inhibits de novo cholesterol biosynthesis. • MMA

  14. Ionic channels and nerve membrane lipids. Cholesterol-tetrodotoxin interaction.

    Science.gov (United States)

    Villegas, R; Barnola, F V; Camejo, G

    1970-04-01

    Experiments were carried out to investigate possible interactions of tetrodotoxin (TTX) with lipid molecules isolated from nerve fiber plasma membranes of the squid Dosidicus gigas. TTX has a highly selective ability to block the channel normally used by Na(+) to cross the axolemma during nervous impulse conduction. In order to investigate the interaction each lipid sample was spread on 5 x 10(-7)M TTX and TTX-free 0.15 M NaCl solutions adjusted to pH 7.4 with 7 x 10(-3)M phosphate buffer. The surface pressure-area diagrams of the lipid monolayers revealed that TTX interacts only with cholesterol. The expansion of the cholesterol monolayers at 5 x 10(-7)M TTX was 2 A(2)/molecule at zero pressure for the experiments at 20 degrees C and 2.5 A(2)/molecule for those at 25 degrees C. Similar results were obtained in KCl subphases. The apparent dissociation constant of the cholesterol-TTX complex calculated from dose-response experiments is 2.6 x 10(-7)M. Experiments at pH 10.1 revealed that the zwitter ionic form of TTX is less active. Experiments with cholesterol derivatives (cholesteryl acetate, cholesterol methyl ether, cholestanol, and cholestanyl acetate) indicate that for the interaction with TTX a partial negatively charged group at C-3 and a double bond between C-5 and C-6 on the steroid nucleus are required. Tetrodonic acid, a biologically inactive derivative of TTX, does not interact with cholesterol. The results lead us to propose that cholesterol is part of the Na(+) channel. PMID:5435784

  15. Measurement of rates of cholesterol synthesis using tritiated water

    International Nuclear Information System (INIS)

    Rates of sterol synthesis in various tissues commonly are assessed by assaying levels of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase on isolated microsomes or by measuring the rates of incorporation of various 14C-labeled substrates or [3H]water into cholesterol by whole cell preparations in vitro or by the tissues of the whole animal in vivo. While measurement of activities of HMG-CoA reductase or rates of incorporation of 14C-labeled substrates into cholesterol give useful relative rates of sterol production, neither method yields absolute rates of cholesterol synthesis. The use of [3H]water circumvents the problem of variable and unknown dilution of the specific activity of the precursor pool encountered when 14C-labeled substrates are used and does yield absolute rates of cholesterol synthesis provided that the 3H/C incorporation ratio is known for a particular tissue. In 12 different experimental situations it has been found that from 21 to 27 micrograms atoms of 3H are incorporated into cholesterol from [3H]water in different tissues of several animal species, so that the 3H/C incorporation ratio is similar under nearly all experimental conditions and varies from 0.78 to 1.00. When administered in vivo, [3H]water rapidly equilibrates with intracellular water and is incorporated into sterols within the various organs at rates that are linear with respect to time. From such data it is possible to obtain absolute rates of cholesterol synthesis in the whole animal and in the various organs of the animal. Current data suggest, therefore, that use of [3H]water yields the most accurate rates of cholesterol synthesis both in vitro and in vivo

  16. Monomethylarsonous acid inhibited endogenous cholesterol biosynthesis in human skin fibroblasts

    International Nuclear Information System (INIS)

    Human exposure to arsenic in drinking water is a widespread public health concern, and such exposure is known to be associated with many human diseases. The detailed molecular mechanisms about how arsenic species contribute to the adverse human health effects, however, remain incompletely understood. Monomethylarsonous acid [MMA(III)] is a highly toxic and stable metabolite of inorganic arsenic. To exploit the mechanisms through which MMA(III) exerts its cytotoxic effect, we adopted a quantitative proteomic approach, by coupling stable isotope labeling by amino acids in cell culture (SILAC) with LC-MS/MS analysis, to examine the variation in the entire proteome of GM00637 human skin fibroblasts following acute MMA(III) exposure. Among the ∼ 6500 unique proteins quantified, ∼ 300 displayed significant changes in expression after exposure with 2 μM MMA(III) for 24 h. Subsequent analysis revealed the perturbation of de novo cholesterol biosynthesis, selenoprotein synthesis and Nrf2 pathways evoked by MMA(III) exposure. Particularly, MMA(III) treatment resulted in considerable down-regulation of several enzymes involved in cholesterol biosynthesis. In addition, real-time PCR analysis showed reduced mRNA levels of select genes in this pathway. Furthermore, MMA(III) exposure contributed to a distinct decline in cellular cholesterol content and significant growth inhibition of multiple cell lines, both of which could be restored by supplementation of cholesterol to the culture media. Collectively, the present study demonstrated that the cytotoxicity of MMA(III) may arise, at least in part, from the down-regulation of cholesterol biosynthesis enzymes and the resultant decrease of cellular cholesterol content. - Highlights: • MMA(III)-induced perturbation of the entire proteome of GM00637 cells is studied. • Quantitative proteomic approach revealed alterations of multiple cellular pathways. • MMA(III) inhibits de novo cholesterol biosynthesis. • MMA

  17. Prenatal Ethanol Exposure Up-Regulates the Cholesterol Transporters ATP-Binding Cassette A1 and G1 and Reduces Cholesterol Levels in the Developing Rat Brain

    OpenAIRE

    Zhou, Chunyan; Chen, Jing; Zhang, Xiaolu; Costa, Lucio G.; Guizzetti, Marina

    2014-01-01

    Aims: Cholesterol plays a pivotal role in many aspects of brain development; reduced cholesterol levels during brain development, as a consequence of genetic defects in cholesterol biosynthesis, leads to severe brain damage, including microcephaly and mental retardation, both of which are also hallmarks of the fetal alcohol syndrome. We had previously shown that ethanol up-regulates the levels of two cholesterol transporters, ABCA1 (ATP binding cassette-A1) and ABCG1, leading to increased cho...

  18. Cholesterol metabolism changes under long-term dietary restrictions while the cholesterol homeostasis remains unaffected in the cortex and hippocampus of aging rats

    OpenAIRE

    Smiljanic, Kosara; Vanmierlo, Tim; Djordjevic, Aleksandra Mladenovic; Perovic, Milka; Ivkovic, Sanja; Luetjohann, Dieter; Kanazir, Selma

    2014-01-01

    Maintaining cholesterol homeostasis in the brain is vital for its proper functioning. While it is well documented that dietary restriction modulates the metabolism of cholesterol peripherally, little is known as to how it can affect cholesterol metabolism in the brain. The present study was designed to elucidate the impact of long-term dietary restriction on brain cholesterol metabolism. Three-month-old male Wistar rats were exposed to long-term dietary restriction until 12 and 24 months of a...

  19. Dietary Cholesterol Affects Plasma Lipid Levels, the Intravascular Processing of Lipoproteins and Reverse Cholesterol Transport without Increasing the Risk for Heart Disease

    OpenAIRE

    Jacqueline Barona; Maria Luz Fernandez

    2012-01-01

    The associations between dietary cholesterol and heart disease are highly controversial. While epidemiological studies and clinical interventions have shown the lack of correlation between cholesterol intake and cardiovascular disease (CVD) risk, there is still concern among health practitioners and the general population regarding dietary cholesterol. In this review, several clinical studies utilizing cholesterol challenges are analyzed in terms of changes that occur in lipoprotein metabolis...

  20. Chylomicron remnant model emulsions induce intracellular cholesterol accumulation and cell death due to lysosomal destabilization.

    Science.gov (United States)

    Wakita, Kyoko; Morita, Shin-ya; Okamoto, Naoko; Takata, Eriko; Handa, Tetsurou; Nakano, Minoru

    2015-05-01

    Chylomicron remnants, which carry dietary fats and cholesterol, play a role in promoting atherosclerosis. Chylomicron remnants are characterized by high cholesterol content at the surface, different from low-density lipoproteins (LDLs) containing high amounts of esterified cholesterol (CE) in the core. We prepared cholesterol-rich emulsions (TO-PC/cholesterol emulsions) as models for chylomicron remnants and compared their effects on J774 macrophages with acetylated-LDL (ac-LDL). Internalization of TO-PC/cholesterol emulsions into macrophages reduced cell viability, whereas ac-LDL did not. Surprisingly, there was no difference in intracellular free cholesterol content between cells incubated with TO-PC/cholesterol emulsions and with ac-LDL. Furthermore, cholesterol in TO-PC/cholesterol emulsions and ac-LDL both were internalized into J774 macrophages; however, incubation with TO-PC/cholesterol emulsions induced leakage of lysosomal protease, cathepsin-L, to cytosol, which was not observed for incubation with ac-LDL. Inhibition of the activity of cathepsin-L recovered the viability of macrophages that ingested TO-PC/cholesterol emulsions. We suggest an alternative fate of cholesterol-rich emulsions taken up by macrophages, which is different from other atherogenic lipoproteins rich in CE; internalization of TO-PC/cholesterol emulsions into macrophages induces rapid free cholesterol accumulation in lysosomes and cell death due to lysosomal destabilization. PMID:25661161

  1. The mechanism of dietary cholesterol effects on lipids metabolism in rats

    Directory of Open Access Journals (Sweden)

    Wang Jing-Feng

    2010-01-01

    Full Text Available Abstract Background Cholesterol administration has been reported to influence hepatic lipid metabolism in rats. In the present study, the effect of dietary cholesterol on hepatic activity and mRNA expression of the enzymes involved in lipid metabolism were investigated. Fourteen male Wistar rats were randomly divided into 2 groups and fed 1% cholesterol or cholesterol free AIN76 diets for 4 weeks. Results The serum triglyceride and high density lipoprotein cholesterol levels were significantly decreased but the total cholesterol and non high density lipoprotein cholesterol levels were significantly increased in the cholesterol-fed rats compared with the control rats. And the concentrations of the hepatic total cholesterol and triglyceride increased about 4-fold and 20-fold separately by dietary cholesterol. The activities of hepatic malic enzyme, glucose-6-phosphate dehydrogenase, fatty acid synthase, phosphatidate phophatase and carnitine palmitoyl transferase were depressed by the cholesterol feeding (40%, 70%, 50%, 15% and 25% respectively. The results of mRNA expression showed that fatty acid synthase, carnitine palmitoyl transferase 1, carnitine palmitoyl transferase 2, and HMG-CoA reductase were down-regulated (35%, 30%, 50% and 25% respectively and acyl-CoA: cholesterol acyltransferase and cholesterol 7α-hydroxylase were up regulated (1.6 and 6.5 folds in liver by the cholesterol administration. Conclusions The dietary cholesterol increased the triglyceride accumulation in liver, but did not stimulate the activity and the gene expression of hepatic enzymes related to triglyceride and fatty acid biosynthesis.

  2. Plasma lipoprotein profiles and arylesterase activities in two inbred strains of rabbits with high or low response of plasma cholesterol to dietary cholesterol

    NARCIS (Netherlands)

    Beynen, A.C.; Katan, M.B.; Zutphen, van L.F.M.

    1984-01-01

    1. 1. Cholesterol feeding for 4 weeks of female and male rabbits of two inbred strains increased plasma cholesterol concentrations by about 11 and 48 mmole/I in the hypo- and hyperresponsive strain, respectively. 2. 2. On the low-cholesterol pre-experimental diet, the hyporesponsive animals had sign

  3. Treatment of young rats with cholestyramine or a hypercholesterolemic diet does not influence the response of serum cholesterol to dietary cholesterol in later life

    NARCIS (Netherlands)

    Beynen, A.C.; Bruijne, J.J. de; Katan, M.B.

    1985-01-01

    Groups of 10 female Wistar rats (aged 4 weeks) were fed for 29 days either a low-cholesterol commercial diet, a commercial diet containing 2% (w/w) cholesterol, 0.5% cholate and 5% olive oil or a diet containing 2% cholestyramine. The rats were then fed the low-cholesterol commercial diet for the ne

  4. Human immunodeficiency virus impairs reverse cholesterol transport from macrophages.

    Directory of Open Access Journals (Sweden)

    Zahedi Mujawar

    2006-10-01

    Full Text Available Several steps of HIV-1 replication critically depend on cholesterol. HIV infection is associated with profound changes in lipid and lipoprotein metabolism and an increased risk of coronary artery disease. Whereas numerous studies have investigated the role of anti-HIV drugs in lipodystrophy and dyslipidemia, the effects of HIV infection on cellular cholesterol metabolism remain uncharacterized. Here, we demonstrate that HIV-1 impairs ATP-binding cassette transporter A1 (ABCA1-dependent cholesterol efflux from human macrophages, a condition previously shown to be highly atherogenic. In HIV-1-infected cells, this effect was mediated by Nef. Transfection of murine macrophages with Nef impaired cholesterol efflux from these cells. At least two mechanisms were found to be responsible for this phenomenon: first, HIV infection and transfection with Nef induced post-transcriptional down-regulation of ABCA1; and second, Nef caused redistribution of ABCA1 to the plasma membrane and inhibited internalization of apolipoprotein A-I. Binding of Nef to ABCA1 was required for down-regulation and redistribution of ABCA1. HIV-infected and Nef-transfected macrophages accumulated substantial amounts of lipids, thus resembling foam cells. The contribution of HIV-infected macrophages to the pathogenesis of atherosclerosis was supported by the presence of HIV-positive foam cells in atherosclerotic plaques of HIV-infected patients. Stimulation of cholesterol efflux from macrophages significantly reduced infectivity of the virions produced by these cells, and this effect correlated with a decreased amount of virion-associated cholesterol, suggesting that impairment of cholesterol efflux is essential to ensure proper cholesterol content in nascent HIV particles. These results reveal a previously unrecognized dysregulation of intracellular lipid metabolism in HIV-infected macrophages and identify Nef and ABCA1 as the key players responsible for this effect. Our findings

  5. The micromethod for determination of cholesterol, cholesteryl esters and phospholipids

    Directory of Open Access Journals (Sweden)

    Okabe,Akinobu

    1974-12-01

    Full Text Available We examined the method for determining microquantities of lipids, including cholesterol, cholesteryl esters and phospholipids. A standard colorimetric procedure of cholesteryl esters was modified to accommodate a quantitative thin-layer chromatography. This method involved the following steps. (1 Separation of lipids by a thin-layer chromatography: Lipids were applied to Silica gel G plates. Plates were developed with petroleum ether-diethyl etheracetic acid (82: 18: 2, vIvIv. (2 Elution of cholesterol and its esters from scraped silica gel: After scraping the silica gel with adhered cholesterol and its esters, they were eluted with chloroform-methanol (4: 1, v,tv. In the case of phspholipids, the silica gel was calcified. (3 Colorimetric determination of the lipids: Cholesterol and its esters eluted from the silica gel were determined by the method of ZAK with ROSENTHAL'S color reagent directly and after saponification, respectively. Phospholipids were calculated from the phosphorous content determined by the method of KATES. On the basis of examination of recovery and analyses of lipids extracted from tissue, it was concluded that this method permitted a reliable estimation of microquantities of cholesterol, its esters and phospholipids from small amounts of biological materials.

  6. [An operative case of cholesterol granuloma of the petrous apex].

    Science.gov (United States)

    Saino, M; Kayama, T; Kuroki, A; Siraisi, Y; Sato, K; Nakai, O

    1996-11-01

    A 59-year-old man presented with a rare cholesterol granuloma of the petrous apex manifesting as headache, left facial dysesthesia, diplopia, left hearing impairment, and left tinnitus. Neurological examination revealed dysesthesia of territory in all divisions of the left trigeminal nerve, left incomplete abducens nerve palsy, left mixed hearing impairment, and left tinnitus. Plain CT scan showed a smoothly marginated mass involving the left petrous apex. The mass was isodense with the brain parenchyma and not enhanced by contrast medium. The mass appeared heterogeneously slightly hyperintense on the T1-weighted MR image and homogeneously hyperintense on the T2-weighted MR image except for the peripheral portion. The mass was not enhanced after intravenous gadolinium DTPA administration. Surgery via a petrosal approach totally removed the mass in the intracranial, extradural space. Histological examination showed typical features of cholesterol granuloma, with cholesterin clefts, hemosiderin deposits, and erythrocytes in non-specific granulation tissue. Cholesterol granuloma most commonly occurs in the middle ear cavity, and rarely in the petrous apex. The characteristic hyperintense appearance of cholesterol granuloma on T1- and T2-weighted MR images is very useful for differentiation from other lesions of the petrous apex and the cerebellopontine angle such as cholesteatoma, mucocele, chordoma, and meningioma. Solid cholesterol granuloma of the petrous apex should be treated by total removal via craniotomy, not by drainage which is commonly performed by otorhinologists. PMID:8934474

  7. Optimizing Conditions to Cholesterol Adsorbed with Carboxymethyl Chitosan

    Directory of Open Access Journals (Sweden)

    Mardiyah Kurniasih

    2016-05-01

    Full Text Available A research on optimizing conditions to cholesterol adsorbed have been performed. Optimization was performed by varying: contact time, adsorbent weight and temperature of the system's. A full factorial experimental design was used in this study. Characterization performed on the synthesized chitosan and carboxymethyl chitosan including FTIR, water content, ash content, solubility, porosity, and swelling effect. The results showed that carboxymethyl chitosan able to adsorb cholesterol under conditions optimal adsorbent with cholesterol ratio (1:200 with a contact time of 90 minutes at temperature of 40 °C. Meanwhile, at a temperature of 55 °C carboxymethyl chitosan capable of adsorb cholesterol under conditions optimal adsorbent with cholesterol ratio (1:300 with a contact time of 30 minutes. Chitosan and carboxymethyl chitosan synthesized has a water content of 7.4 and 10.2%, ash content of 0.14 and 2.29%, solubility in distilled water at 1.10-5and 1.98.10-3%, solubility in acetic acid 0.02 and 0.04%, porosity at 88.3% and 88.8%, and swelling at 163.13 and 182.98%.

  8. 3 Benzyl-6-chloropyrone: a suicide inhibitor of cholesterol esterase

    International Nuclear Information System (INIS)

    Cholesterol, absorbed from the intestine, appears in lymph as the ester. Cholesterol esterase is essential for this process, since depletion of the enzyme blocks and repletion restores, absorption. Selective inhibitors of cholesterol esterase may thus prove useful in reducing cholesterol uptake. A series of potential suicide substrates were synthesized which, following cleavage by the enzyme, would attack the putative nucleophile in the active site. One of these, 3-benzyl-6-chloropyrone (3BCP), inhibited both synthesis and hydrolysis of 14C-cholesteryl oleate with an I50 of approximately 150 μM. The inactivation was time-dependent and characteristic of a suicide mechanism. The α pyrone structure (lactone analog) is cleaved by a serine-hydroxyl in the active site. This generates an enoyl chloride which inactivates the imidazole believed to play a part in the catalytic function of the enzyme. Inhibition by 3BCP is selective for cholesterol esterase. The activity of pancreatic lipase as not affected by concentrations up to 1 mM

  9. Treating elevated cholesterol levels: the great Satan in perspective.

    Science.gov (United States)

    Gibaldi, M; Kradjan, W

    1996-03-01

    The purpose of this review is to provide perspective on the developments leading to the recognition of high cholesterol levels as a risk factor for coronary heart disease (CHD). Another objective is to consider the unfolding controversies regarding the relative value of cholesterol-lowering drug therapy in primary and secondary prevention. Should physicians use lipid-lowering drugs to treat patients with elevated cholesterol levels but no clinical evidence of coronary disease, or limit intervention to patients with a previous history of angina, coronary angioplasty, coronary artery bypass surgery, or myocardial infarction? This review finds inadequate data to support a recommendation for screening large populations for the presence of elevated cholesterol levels or for primary prevention in those known to have high cholesterol. On the other hand, there is mounting evidence to support vigorous intervention in those with known coronary disease. Further study is needed to determine whether a subset of patients with one or more well-defined risk factors would benefit from primary prevention. PMID:8690811

  10. Cholesterol crystal embolization diagnosed on bladder transurethral resection.

    Science.gov (United States)

    Chatelain, Denis; Cordonnier, Carole; Brevet, Marie; Petit, Jacques; Sevestre, Henri

    2005-08-01

    Cholesterol crystal embolization (CCE) is a severe systemic disorder caused by vascular migration of cholesterol crystals originating from ulcerative atherosclerotic plaques located in large arteries. We report 2 cases of CCE diagnosed on bladder transurethral resection in 2 men aged 94 and 72 years. Both patients had atherosclerosis disease. One patient had been treated by heparin 1 month before for pulmonary embolism and the other had had a coronary angiography and bypass graft surgery 5 months before for silent myocardial infarction. One patient presented with hematuria and the other with acute renal failure. Cystoscopy showed multiple papillary tumors of the bladder wall. Bladder transurethral resections showed transitional cell carcinoma with cholesterol crystals occluding the lumen of small arterioles in the submucosa. Eight cases of CCE in the bladder wall have been reported in the literature in 3 women and 5 men aged 56 to 79 years. Cholesterol crystal embolization is often discovered in the bladder wall on necropsy specimens. Only 2 cases have been fortuitously discovered on bladder transurethral resection performed for transitional cell carcinoma. Cholesterol crystal embolization in the bladder wall is often a marker of severe disease although the evolution is quite favorable in our patients, still alive 1 and 2 years after diagnosis. PMID:16084459

  11. The fate of chylomicron cholesterol in the rat. 1. research into the storing of chylomicrons (1961)

    International Nuclear Information System (INIS)

    Rats conditioned to take their dally meal between midnight and 2 a.m. are given at midnight, by stomach tubing, 0,5 mg 4-14C-cholesterol, and are sacrificed in the following hours. During the most active phase of intestinal absorption, specific radioactivities of free and esterified liver cholesterol and of serum cholesterol are practically equal. Consequently, captation of absorbed cholesterol by the liver is not detectable. The results obtained exclude, on the other hand, the possibility that the lungs might play a similar role. The problem of the fate of chylomicron cholesterol is discussed. In order to avoid any ambiguity in this discussion, we have determined the concentration and specific radioactivity of free and esterified cholesterol in chylomicrons and lymph obtained by continuous drainage of chyle. 5 p. 100 of the radioactive cholesterol of chyle are found in lymph: in chylomicrons, the radioactivity of free cholesterol is higher than that of esterified cholesterol. (authors)

  12. Cholesterol transfer from normal and atherogenic low density lipoproteins to Mycoplasma membranes

    International Nuclear Information System (INIS)

    The purpose of this study was to determine whether the free cholesterol of hypercholesterolemic low density lipoprotein from cholesterol-fed nonhuman primates has a greater potential for surface transfer to cell membranes than does the free cholesterol of normal low density lipoprotein. The low density lipoproteins were isolated from normal and hypercholesterolemic rhesus and cynomolgus monkeys, incubated with membranes from Acholeplasma laidlawii, a mycoplasma species devoid of cholesterol in its membranes, and the mass transfer of free cholesterol determined by measuring membrane cholesterol content. Since these membranes neither synthesize nor esterify cholesterol, nor degrade the protein or cholesterol ester moieties of low density lipoprotein, they are an ideal model with which to study differences in the cholesterol transfer potential of low density lipoprotein independent of the uptake of the intact low density lipoprotein particle. These studies indicate that, even though there are marked differences in the cholesterol composition of normal and hypercholesterolemic low density lipoproteins, this does not result in a greater chemical potential for surface transfer of free cholesterol. Consequently, if a difference in the surface transfer of free cholesterol is responsible for the enhanced ability of hypercholesterolemic low density lipoprotein to promote cellular cholesterol accumulation and, perhaps, also atherosclerosis, it must be the result of differences in the interaction to the hypercholesterolemic low density lipoprotein with the more complicated mammalian cell membranes, rather than differences in the chemical potential for cholesterol transfer

  13. Influence of molecular packing and phospholipid type on rates of cholesterol exchange

    International Nuclear Information System (INIS)

    The rates of [14C]cholesterol transfer from small unilamellar vesicles containing cholesterol dissolved in bilayers of different phospholipids have been determined to examine the influence of phospholipid-cholesterol interactions on the rate of cholesterol desorption from the lipid-water interface. At 370C, for vesicles containing 10 mol % cholesterol, the half-times for exchange are about 1, 13, and 80 h, respectively, for unsaturated PC, saturated PC, and SM. In order to probe how differences in molecular packing in the bilayers cause the rate constants for cholesterol desorption to be in the order unsaturated PC > saturated PC > SM, nuclear magnetic resonance (NMR) and monolayer methods were used to evaluate the cholesterol physical state and interactions with phospholipid. The NMR relaxation parameters for [4-13C] cholesterol reveal no differences in molecular dynamics in the above bilayers. The greater van der Waals interaction in the SM monolayer (or bilayer) compared to PC gives rise to a larger condensation by cholesterol. This is a direct demonstration of the greater interaction of cholesterol with SM compared to PC. An estimate of the van der Waals interactions between cholesterol and these phospholipids has been used to derive a relationship between the ratio of the rate constants for cholesterol desorption and the relative molecular areas (lateral packing density) in two bilayers. This analysis suggests that differences in cholesterol-phospholipid van der Waals interaction energy are an important cause of varying rates of cholesterol exchange from different host phospholipid bilayers

  14. Effects of Lowering LDL Cholesterol on Progression of Kidney Disease

    DEFF Research Database (Denmark)

    Haynes, Richard; Lewis, David; Emberson, Jonathan;

    2014-01-01

    Lowering LDL cholesterol reduces the risk of developing atherosclerotic events in CKD, but the effects of such treatment on progression of kidney disease remain uncertain. Here, 6245 participants with CKD (not on dialysis) were randomly assigned to simvastatin (20 mg) plus ezetimibe (10 mg) daily...... or matching placebo. The main prespecified renal outcome was ESRD (defined as the initiation of maintenance dialysis or kidney transplantation). During 4.8 years of follow-up, allocation to simvastatin plus ezetimibe resulted in an average LDL cholesterol difference (SEM) of 0.96 (0.02) mmol.......2%] events with placebo; rate ratio, 0.93; 95% CI, 0.86 to 1.01; P=0.09). Exploratory analyses also showed no significant effect on the rate of change in eGFR. Lowering LDL cholesterol by 1 mmol/L did not slow kidney disease progression within 5 years in a wide range of patients with CKD....

  15. biosynthesis of extracellular cholesterol oxidase by irradiated streptomyces species

    International Nuclear Information System (INIS)

    streptomyces sp.culture produced extracellular cholesterol oxidase (COD)at favorable conditions (o.5 g/L cholesterol. 200 Gy, 300 C, ph 7 and 100 r.p.m) at the end of 6 days incubation period. an extracellular enzyme activity (cholesterol degradation %) of 95.36 was achieved during the stationary phase, a specific activity of 1.34 e.u was possible by (NH4)2SO4 precipitation, 1.7 by ultrafiltration and 4.1 E.U/mg protein by sephadex G100 column . COD was stable over a ph range of 6-9 for 1 h .at 300C, the enzyme was also stable up 400C it retained 95.4% of the original activity but when heated up to 500C for 1 h it retained only 65% of the original activity

  16. High levels of confusion for cholesterol awareness campaigns.

    Science.gov (United States)

    Hall, Danika V

    2008-09-15

    Earlier this year, two industry-sponsored advertising campaigns for cholesterol awareness that target the general public were launched in Australia. These campaigns aimed to alert the public to the risks associated with having high cholesterol and encouraged cholesterol testing for wider groups than those specified by the National Heart Foundation. General practitioners should be aware of the potential for the two campaigns to confuse the general public as to who should be tested, and where. The campaign sponsors (Unilever Australasia and Pfizer) each have the potential to benefit by increased market share for their products, and increased profits. These disease awareness campaigns are examples of what is increasingly being termed "condition branding" by pharmaceutical marketing experts. PMID:18803537

  17. The Observation of Highly Ordered Domains in Membranes with Cholesterol

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, Clare L [McMaster University; Marquardt, Drew [Brock University, St. Catharines, ON, Canada; Dies, Hannah [McMaster University; Kucerka, Norbert [Canadian Neutron Beam Centre and Comelius University (Slovakia); Yamani, Zahra [Canadian Neutron Beam Centre, National Research Council, Chalk River Laboratorie; Harroun, Thad [Brock University, St. Catharines, ON, Canada; Katsaras, John [ORNL; Shi, A-C [McMaster University; Rheinstadter, Maikel C [McMaster University

    2013-01-01

    Rafts, or functional domains, are transient nano- or mesoscopic structures in the exoplasmic leaflet of the plasma membrane, and are thought to be essential for many cellular processes. Using neutron diffraction and computer modelling, we present evidence for the existence of highly ordered lipid domains in the cholesterol-rich (32.5 mol%) liquid-ordered (lo) phase of dipalmitoylphosphatidylcholine membranes. The liquid ordered phase in one-component lipid membranes has previously been thought to be a homogeneous phase. The presence of highly ordered lipid domains embedded in a disordered lipid matrix implies non-uniform distribution of cholesterol between the two phases. The experimental results are in excellent agreement with recent computer simulations of DPPC/cholesterol complexes [Meinhardt, Vink and Schmid (2013). Proc Natl Acad Sci USA 110(12): 4476 4481], which reported the existence of nanometer size lo domains in a liquid disordered lipid environment.

  18. Synthesis of the oxysterol, 24(S), 25-epoxycholesterol, parallels cholesterol production and may protect against cellular accumulation of newly-synthesized cholesterol

    OpenAIRE

    Brown Andrew J; Quinn Carmel M; Wong Jenny

    2007-01-01

    Abstract Aim The effects of 24(S),25-epoxycholesterol (24,25EC) on aspects of cholesterol homeostasis is well-documented. When added to cells, 24,25EC decreases cholesterol synthesis and up-regulates cholesterol efflux genes, including ABCA1. Synthesis of 24,25EC occurs in a shunt of the mevalonate pathway which also produces cholesterol. Therefore, 24,25EC synthesis should be subject to the same negative feedback regulation as cholesterol synthesis. To date, no role has been ascribed to 24,2...

  19. Preparation of a Polypyrrole-Polyvinylsulphonate Composite Film Biosensor for Determination of Cholesterol Based on Entrapment of Cholesterol Oxidase

    Directory of Open Access Journals (Sweden)

    Ahmet Yaşar

    2009-08-01

    Full Text Available In this paper, a novel amperometric cholesterol biosensor with immobilization of cholesterol oxidase on electrochemically polymerized polypyrrole–polyvinylsulphonate (PPy–PVS films has been accomplished via the entrapment technique on the surface of a platinum electrode. Electropolymerization of pyrrole and polyvinylsulphonate on the Pt surface was carried out by cyclic voltammetry between -1.0 and +2.0 V (vs. Ag/AgCl at a scan rate of 100 mV upon the Pt electrode with an electrochemical cell containing pyrrole and polyvinylsulphonate. The amperometric determination is based on the electrochemical detection of H2O2 generated in the enzymatic reaction of cholesterol. Determination of cholesterol was carried out by the oxidation of enzymatically produced H2O2 at 0.4 V vs. Ag/AgCl. The effects of pH and temperature were investigated and optimum parameters were found to be 7.25 and 35 °C, respectively. The storage stability and operational stability of the enzyme electrode were also studied. The results show that 32% of the response current was retained after 19 activity assays. The prepared cholesterol biosensor retained 43% of initial activity after 45 days when stored in 0.1 M phosphate buffer solution at 4 °C.

  20. Intracellular cholesterol transport proteins enhance hydrolysis of HDL-CEs and facilitate elimination of cholesterol into bile.

    Science.gov (United States)

    Wang, Jing; Bie, Jinghua; Ghosh, Shobha

    2016-09-01

    While HDL-associated unesterified or free cholesterol (FC) is thought to be rapidly secreted into the bile, the fate of HDL-associated cholesteryl esters (HDL-CEs) that represent >80% of HDL-cholesterol, is only beginning to be understood. In the present study, we examined the hypothesis that intracellular cholesterol transport proteins [sterol carrier protein 2 (SCP2) and fatty acid binding protein-1 (FABP1)] not only facilitate CE hydrolase-mediated hydrolysis of HDL-CEs, but also enhance elimination of cholesterol into bile. Adenovirus-mediated overexpression of FABP1 or SCP2 in primary hepatocytes significantly increased hydrolysis of HDL-[(3)H]CE, reduced resecretion of HDL-CE-derived FC as nascent HDL, and increased its secretion as bile acids. Consistently, the flux of [(3)H]cholesterol from HDL-[(3)H]CE to biliary bile acids was increased by overexpression of SCP2 or FABP1 in vivo and reduced in SCP2(-/-) mice. Increased flux of HDL-[(3)H]CE to biliary FC was noted with FABP1 overexpression and in SCP2(-/-) mice that have increased FABP1 expression. Lack of a significant decrease in the flux of HDL-[(3)H]CE to biliary FC or bile acids in FABP1(-/-) mice indicates the likely compensation of its function by an as yet unidentified mechanism. Taken together, these studies demonstrate that FABP1 and SCP2 facilitate the preferential movement of HDL-CEs to bile for final elimination. PMID:27381048

  1. Urotensin II promotes atherosclerosis in cholesterol-fed rabbits.

    Directory of Open Access Journals (Sweden)

    Yafeng Li

    Full Text Available Urotensin II (UII is a vasoactive peptide composed of 11 amino acids that has been implicated to contribute to the development of cardiovascular disease. The purpose of this study was to investigate whether UII affects the development of atherosclerosis in cholesterol-fed rabbits. UII was infused for 16 weeks through an osmotic mini-pump into male Japanese White rabbits fed on a high-cholesterol diet. Plasma lipids and body weight were measured every 4 weeks. Aortic atherosclerotic lesions along with cellular components, collagen fibers, matrix metalloproteinase-1 and -9 were examined. Moreover, vulnerability index of atherosclerotic plaques was evaluated. UII infusion significantly increased atherosclerotic lesions within the entire aorta by 21% over the control (P = 0.013. Atherosclerotic lesions were increased by 24% in the aortic arch (P = 0.005, 11% in the thoracic aorta (P = 0.054 and 18% in the abdominal aorta (P = 0.035. These increases occurred without changes in plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or body weight. Immunohistochemical staining revealed that macrophages and matrix metalloproteinase-9 were significantly enhanced by 2.2-fold and 1.6-fold in UII group. In vitro studies demonstrated that UII up-regulated the expression of vascular cell adhesion protein-1 and intercellular adhesion molecule-1 in human umbilical vein endothelial cells, which was inhibited by the UII receptor antagonist urantide. In conclusion, our results showed that UII promotes the development of atherosclerotic lesions and destabilizes atherosclerotic plaques in cholesterol-fed rabbits.

  2. Ezetimibe Promotes Brush Border Membrane-to-Lumen Cholesterol Efflux in the Small Intestine

    Science.gov (United States)

    Nakano, Takanari; Inoue, Ikuo; Takenaka, Yasuhiro; Ono, Hiraku; Katayama, Shigehiro; Awata, Takuya; Murakoshi, Takayuki

    2016-01-01

    Ezetimibe inhibits Niemann-Pick C1-like 1 (NPC1L1), an apical membrane cholesterol transporter of enterocytes, thereby reduces intestinal cholesterol absorption. This treatment also increases extrahepatic reverse cholesterol transport via an undefined mechanism. To explore this, we employed a trans-intestinal cholesterol efflux (TICE) assay, which directly detects circulation-to-intestinal lumen 3H-cholesterol transit in a cannulated jejunal segment, and found an increase of TICE by 45%. To examine whether such increase in efflux occurs at the intestinal brush border membrane(BBM)-level, we performed luminal perfusion assays, similar to TICE but the jejunal wall was labelled with orally-given 3H-cholesterol, and determined elevated BBM-to-lumen cholesterol efflux by 3.5-fold with ezetimibe. Such increased efflux probably promotes circulation-to-lumen cholesterol transit eventually; thus increases TICE. Next, we wondered how inhibition of NPC1L1, an influx transporter, resulted in increased efflux. When we traced orally-given 3H-cholesterol in mice, we found that lumen-to-BBM 3H-cholesterol transit was rapid and less sensitive to ezetimibe treatment. Comparison of the efflux and fractional cholesterol absorption revealed an inverse correlation, indicating the efflux as an opposite-regulatory factor for cholesterol absorption efficiency and counteracting to the naturally-occurring rapid cholesterol influx to the BBM. These suggest that the ezetimibe-stimulated increased efflux is crucial in reducing cholesterol absorption. Ezetimibe-induced increase in cholesterol efflux was approximately 2.5-fold greater in mice having endogenous ATP-binding cassette G5/G8 heterodimer, the major sterol efflux transporter of enterocytes, than the knockout counterparts, suggesting that the heterodimer confers additional rapid BBM-to-lumen cholesterol efflux in response to NPC1L1 inhibition. The observed framework for intestinal cholesterol fluxes may provide ways to modulate the flux

  3. Implications of the obesity epidemic for lipid-lowering therapy: Non-HDL cholesterol should replace LDL cholesterol as the primary therapeutic target

    Directory of Open Access Journals (Sweden)

    Michel R Hoenig

    2008-05-01

    Full Text Available Michel R HoenigRoyal Brisbane and Women’s Hospital, Herston, Queensland, AustraliaAbstract: Obesity, metabolic syndrome and diabetes are conditions with increasing prevalence around the world. Cardiovascular risk in diabetics is often so high as to overlap with event rates observed in those with established coronary disease and this has lead to diabetes being classified as a coronary risk equivalent. However, despite the elevated risk of cardiovascular events associated with diabetes and the metabolic syndrome, these patients often have normal low density lipoprotein (LDL cholesterol despite frequent increases in apolipoprotein B, triglycerides and nonhigh density lipoprotein (HDL cholesterol. In contrast to LDL cholesterol, non-HDL cholesterol represents cardiovascular risk across all patient populations but is currently only recommended as a secondary target of therapy by the ATP III report for patients with hypertriglyceridemia. This article provides an overview of the studies that shown non-HDL cholesterol to be superior to LDL cholesterol in predicting cardiovascular events and presents the case for non-HDL cholesterol being the more appropriate primary target of therapy in the context of the obesity pandemic. Adopting non-HDL cholesterol as the primary therapeutic target for all patients will conceivably lead to an appropriate intensification of therapy for high risk patients with low LDL cholesterol.Keywords: obesity, coronary artery disease, non-HDL cholesterol, LDL cholesterol, metabolic syndrome, diabetes

  4. Cholesterol gallstone disease: focusing on the role of gallbladder.

    Science.gov (United States)

    Chen, Yongsheng; Kong, Jing; Wu, Shuodong

    2015-02-01

    Gallstone disease (GSD) is one of the most common biliary tract diseases worldwide in which both genetic and environmental factors have roles in its pathogenesis. Biliary cholesterol supersaturation from metabolic defects in the liver is traditionally seen as the main pathogenic factor. Recently, there have been renewed investigative interests in the downstream events that occur in gallbladder lithogenesis. This article focuses on the role of the gallbladder in the pathogenesis of cholesterol GSD (CGD). Various conditions affecting the crystallization process are discussed, such as gallbladder motility, concentrating function, lipid transport, and an imbalance between pro-nucleating and nucleation inhibiting proteins. PMID:25502177

  5. Orbitofrontal cholesterol granuloma: percutaneous endoscopic-assisted curettage.

    Science.gov (United States)

    Selva, Dinesh; Lai, Tze; Krishnan, Suren

    2003-11-01

    This paper describes the use of endoscopic visualization in curettage of orbital cholesterol granuloma (OCG). Two males aged 54 and 50 years presented with orbitofrontal cholesterol granulomas arising in the superolateral frontal bone and abutting the dura. The granulomas were approached via a superior eyelid crease incision and a 70 degree rigid endoscope was used to visualize curettage of the granuloma from the inner surface of the frontal bone and the dura. Both patients made an uncomplicated recovery and there was no recurrence at eight months and two years follow up. Percutaneous endoscopic curettage is an alternative to blind curettage, lateral orbitotomy or frontal craniotomy for OCG. PMID:14670153

  6. Remnant Cholesterol, Low-Density Lipoprotein Cholesterol, and Blood Pressure as Mediators From Obesity to Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Smith, George Davey;

    2015-01-01

    lipoproteins, blood pressure, glucose, and C-reactive protein. METHODS AND RESULTS: Approximately 90 000 participants from Copenhagen were included in a Mendelian randomization design with mediation analyses. Associations were examined using conventional measurements of body mass index and intermediate...... pressure, and possibly also through elevated nonfasting glucose levels; however, reduced high-density lipoprotein cholesterol and elevated C-reactive protein levels were not mediators in genetic analyses. The 3 intermediate variables that explained the highest excess risk of IHD from genetically determined...... obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. CONCLUSIONS: The increased IHD risk because of...

  7. A role for 1-acylglycerol-3-phosphate-O-acyltransferase-1 in myoblast differentiation.

    Science.gov (United States)

    Subauste, Angela R; Elliott, Brandon; Das, Arun K; Burant, Charles F

    2010-01-01

    AGPAT isoforms catalyze the acylation of lysophosphatidic acid (LPA) to form phosphatidic acid (PA). AGPAT2 mutations are associated with defective adipogenesis. Muscle and adipose tissue share common precursor cells. We investigated the role of AGPAT isoforms in skeletal muscle development. We demonstrate that small interference RNA-mediated knockdown of AGPAT1 expression prevents the induction of myogenin, a key transcriptional activator of the myogenic program, and inhibits the expression of myosin heavy chain. This effect is rescued by transfection with AGPAT1 but not AGPAT2. Knockdown of AGPAT2 has no effect. The regulation of myogenesis by AGPAT1 is associated with alterations on actin cytoskeleton. The role of AGPAT1 on actin cytoskeleton is further supported by colocalization of AGPAT1 to areas of active actin polymerization. AGPAT1 overexpression was not associated with an increase in PA levels. Our observations strongly implicate AGPAT1 in the development of skeletal muscle, specifically to terminal differentiation. These findings are linked to the regulation of actin cytoskeleton. PMID:20561744

  8. A role for 1-acylglycerol-3-phosphate-O-acyltransferase-1 in myoblast differentiation

    OpenAIRE

    Subauste, Angela R; Elliott, Brandon; Das, Arun K.; Burant, Charles F.

    2010-01-01

    AGPAT isoforms catalyze the acylation of lysophosphatidic acid (LPA) to form phosphatidic acid (PA). AGPAT2 mutations are associated with defective adipogenesis. Muscle and adipose tissue share common precursor cells. We investigated the role of AGPAT isoforms in skeletal muscle development. We demonstrate that small interference RNA-mediated knockdown of AGPAT1 expression prevents the induction of myogenin, a key transcriptional activator of the myogenic program, and inhibits the expression ...

  9. Longitudinal Trajectories of Cholesterol from Midlife through Late Life according to Apolipoprotein E Allele Status

    Directory of Open Access Journals (Sweden)

    Brian Downer

    2014-10-01

    Full Text Available Background: Previous research indicates that total cholesterol levels increase with age during young adulthood and middle age and decline with age later in life. This is attributed to changes in diet, body composition, medication use, physical activity, and hormone levels. In the current study we utilized data from the Framingham Heart Study Original Cohort to determine if variations in apolipoprotein E (APOE, a gene involved in regulating cholesterol homeostasis, influence trajectories of total cholesterol, HDL cholesterol, and total: HDL cholesterol ratio from midlife through late life. Methods: Cholesterol trajectories from midlife through late life were modeled using generalized additive mixed models and mixed-effects regression models. Results: APOE e2+ subjects had lower total cholesterol levels, higher HDL cholesterol levels, and lower total: HDL cholesterol ratios from midlife to late life compared to APOE e3 and APOE e4+ subjects. Statistically significant differences in life span cholesterol trajectories according to gender and use of cholesterol-lowering medications were also detected. Conclusion: The findings from this research provide evidence that variations in APOE modify trajectories of serum cholesterol from midlife to late life. In order to efficiently modify cholesterol through the life span, it is important to take into account APOE allele status.

  10. Cholesterol efflux monitoring in macrophage form cells by using fluorescence lifetime imaging

    Science.gov (United States)

    Song, Young Sik; Lee, Sang Hak; Park, Byoung Hee; Kim, Soo Hyeok; Hwang, Won Sang; Kim, Dug Young

    2015-03-01

    Macrophages play a key role in atherosclerotic plaque destabilization and rupture, since they accumulate large amounts of lipid through the uptake of modified lipoproteins which results in foam cell formation. Cholesterol efflux is the process of removing cholesterol from macrophages in the subintima of the vessel wall, and efflux mechanism in a cell is one of the critical issues for the prevention of cardiovascular diseases. High density lipoproteins (HDL) stimulate cholesterol efflux from macrophage foam cells in the arterial wall. Radioisotope-labeled cholesterol analysis method is well known conventional method for observing cholesterol efflux. The major drawback of this method is its long and complicated process. Fluorescence intensity imaging schemes are replacing the radioisotope-labeled method in recent years for cholesterol efflux monitoring. Various spectroscopic methods are also adapted for cholesterol efflux imaging. Here we present a fluorescence lifetime imaging method for more quantitative observation of cholesterol efflux process in macrophages, which enables us to observe cholesterol level changes with various conditions. We used J774 macrophage cell and 25-NBD-cholesterol which is a famous cholesterol specific dye. Our lifetime imaging results clearly show cholesterol efflux rate very effectively. We believe that fluorescence lifetime analysis is new and very powerful for cholesterol imaging or monitoring.

  11. Treatment with methotrexate inhibits atherogenesis in cholesterol-fed rabbits.

    Science.gov (United States)

    Bulgarelli, Adriana; Martins Dias, Adriana Abalen; Caramelli, Bruno; Maranhão, Raul Cavalcante

    2012-04-01

    A decrease in the number of cardiovascular events in patients with rheumatoid arthritis or psoriasis treated with methotrexate (MTX) has been observed in the literature. The aim of this study was to test whether MTX could promote anti-inflammatory effects and reduce the atherosclerotic lesions in rabbits with atherosclerosis induced by cholesterol feeding. Twenty male New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30 of cholesterol feeding, 10 animals were treated with 4 weekly intravenous injections of MTX (4 mg/kg) and 10 with 4 weekly saline solution injections for 30 days. MTX reduced the size of the lesion areas of cholesterol-fed animals by 75% and intima-media ratio 2-fold. The drug inhibited macrophage migration into the intima by 50% and the presence of apoptotic cells by 84% but did not inhibit the intimal proliferation of smooth muscle cells. MTX treatment also diminished the positive staining area of metalloproteinase 9 in the intima, which is probably beneficial. In the tumor necrosis factor-α-treated human umbilical vein endothelial cell line, incubation with MTX led to downregulation of 5 pro-inflammatory genes, TNF-α, VAP-1, IL-1β, CXCL2, and TLR2, and upregulation of the anti-inflammatory TGF-β1 gene, thus showing endothelium-protective properties. In conclusion, MTX showed direct in vivo anti-atherosclerotic action and may have potential in the treatment of this disorder. PMID:22113347

  12. Plasma HDL cholesterol and risk of myocardial infarction

    DEFF Research Database (Denmark)

    Voight, Benjamin F; Peloso, Gina M; Orho-Melander, Marju;

    2012-01-01

    High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes......, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal....

  13. Influence of dietary proteins on cholesterol metabolism and nephrocalcinosis.

    NARCIS (Netherlands)

    Zhang, X.

    1992-01-01

    This thesis consists of two parts. The first part deals with the effects of type and amount of various animal proteins on plasma and liver cholesterol concentrations in female, weanling rats. The second part focusses on the nephrocalcinogenic effects of dietary proteins in female rats.Chapter 1 pres

  14. 21 CFR 862.1175 - Cholesterol (total) test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cholesterol (total) test system. 862.1175 Section 862.1175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  15. Zymosan-mediated inflammation impairs in vivo reverse cholesterol transport.

    Science.gov (United States)

    Malik, Priya; Berisha, Stela Z; Santore, Jennifer; Agatisa-Boyle, Colin; Brubaker, Gregory; Smith, Jonathan D

    2011-05-01

    Inflammation has been proposed to impair HDL function and reverse cholesterol transport (RCT). We investigated the effects of inflammation mediated by zymosan, a yeast glucan, on multiple steps along the RCT pathway in vivo and ex vivo. Acute inflammation with 70 mg/kg zymosan impaired RCT to plasma, liver, and feces similarly by 17-22% (P < 0.05), with no additional block at the liver. Hepatic gene expression further demonstrated no change in ABCG5, ABCB4, and ABCB11 expression but a decline in ABCG8 mRNA (32% P < 0.05). Plasma from zymosan-treated mice had a 21% decrease in cholesterol acceptor ability (P < 0.01) and a 35% decrease in ABCA1-specific efflux capacity (P < 0.01) in vitro. Zymosan treatment also decreased HDL levels and led to HDL remodeling with increased incorporation of serum amyloid A. In addition, cholesterol efflux from cultured macrophages declined with zymosan treatment in a dose dependent manner. Taken together, our results suggest that zymosan impairs in vivo RCT primarily by decreasing macrophage-derived cholesterol entering the plasma, with minimal additional blocks downstream. Our study supports the notion that RCT impairment is one of the mechanisms for the increased atherosclerotic burden observed in inflammatory conditions. PMID:21335620

  16. Endosomal cholesterol trafficking: protein factors at a glance

    Institute of Scientific and Technical Information of China (English)

    Ximing Du; Hongyuan Yang

    2013-01-01

    The delivery of low-density lipoprotein-derived cholesterol (LDL-C) from endosomal compartments to the plasma membrane and the endoplasmic reticulum (ER) is an important yet poorly understood cellular process.NiemannPick C1 (NPC1),a multi-pass integral membrane protein on the limiting membranes of late endosomes (LE)/lysosomes (Ly),is known to insert lumenal LDL-C to the limiting membrane of LE/Ly.Recent progress has identified novel cytoplasmic proteins that regulate the exit of LDL-C from LE/Ly,such as ORP5,a member of the oxysterolbinding protein-related protein (ORPs) family,and Hrs/VPS27,a well-established regulator of the endosomal sorting complex required for transport pathway.Whereas ORP5/ORPs may serve as cytosolic cholesterol carriers and deliver cholesterol in a non-vesicular manner,how Hrs/VPS27 regulate endosomal cholesterol sorting remains enigmatic.We discuss the functional relationship between NPC1,Hrs,and ORP5,and formulate possible schemes on how LDL-C may be moved from endosomal compartments to other cellular organelles.

  17. Effect of cholesterol supplementation on cryosurvival of goat spermatozoa

    Directory of Open Access Journals (Sweden)

    Sunita Behera

    2015-12-01

    Full Text Available Aim: Sperm membrane cholesterol influences cryodamage during cryopreservation. The present study was carried out to evaluate the effect of varying cholesterol levels in Tris based extenders on the freezability of sexually healthy Malabari buck semen. Materials and Methods: A total of 48 ejaculates from two adults healthy sexually healthy Malabari bucks were utilized for the study. The collected and pooled ejaculates were divided into four groups with Group I serving as Control - I, Group II and III were treated with 1 mg and 2 mg of cholesterol-loaded-cyclodextrin (CLC/120 × 106 spermatozoa, respectively, and Group IV treated with 1 mg methyl-β-cyclodextrin (MβCD served as Control - II. Manual freezing was carried out to cryopreserve the treated and control spermatozoa. Results: Treatment of semen samples with CLC resulted in improved maintenance of sperm motility at pre-freeze and post-thaw stages of cryopreservation without affecting hypo-osmotic swelling response. Treatment of semen with 1 mg of CLC/120 × 106 spermatozoa was observed to be better than treatment with 2 mg of CLC/120 × 106 spermatozoa. In general, MβCD treatment was found to result in significantly lower sperm characteristics than those of Control - I and CLC treatment at pre-feeze and post-thaw stages and when incubated up to 4 h. Conclusion: Cholesterol treatment of sexually healthy Malabari buck semen was found to hold promise for improving cryopreser-vability of spermatozoa.

  18. LDL cholesterol goals and cardiovascular risk during statin treatment

    DEFF Research Database (Denmark)

    Olsson, Anders G; Lindahl, Christina; Holme, Ingar;

    2011-01-01

    We assessed the proportion of patients treated with either simvastatin 20 or 40 mg or atorvastatin 80 mg who achieved low-density lipoprotein cholesterol (LDL-C) goals of 2.5 or 2.0 mmol/l in the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study. We explored how...

  19. The effect of lowering LDL cholesterol on vascular access patency

    DEFF Research Database (Denmark)

    Herrington, William; Emberson, Jonathan; Staplin, Natalie;

    2014-01-01

    BACKGROUND AND OBJECTIVES: Reducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of major atherosclerotic events among patients with CKD, including dialysis patients, but the effect of lowering LDL-C on vascular access patency is unclear. DESIGN, SETTING, PARTICIPANTS...

  20. Low-density lipoprotein cholesterol and risk of gallstone disease

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, Ruth; Benn, Marianne;

    2013-01-01

    Drugs which reduce plasma low-density lipoprotein cholesterol (LDL-C) may protect against gallstone disease. Whether plasma levels of LDL-C per se predict risk of gallstone disease remains unclear. We tested the hypothesis that elevated LDL-C is a causal risk factor for symptomatic gallstone...

  1. Cholesterol and Alzheimer Type Dementia among Adults with Down Syndrome

    Science.gov (United States)

    Buckley, Frank

    2008-01-01

    This article reports a summary of research by Warren Zigman and colleagues investigating the link between cholesterol levels and Alzheimer type dementia among adults with Down syndrome. Warren Zigman and colleagues followed 123 adults with Down syndrome between May 1998 and April 2006. The participants were aged between 41 and 78 years at the…

  2. Investigating structural details of lipid-cholesterol-A β interactions

    Science.gov (United States)

    Rai, Durgesh; Anunciado, Divina; Heller, William; O'Neill, Hugh; Urban, Volker; Qian, Shuo

    2015-03-01

    Alzheimer's disease (AD) is the most common form of dementia and is predicted to affect 1 in 85 people around the world by 2050. Amyloid beta (A β) -peptide, a peptide composed of 40- 42 amino acids that is the product of cleavage from the amyloid precursor protein (APP), is regarded to play a major role in the development of AD. In addition, accumulating evidence points to a positive association between cholesterol and AD. Here, we present results from our studies about A β-peptide and cholesterol in bilayer by small-angle neutron scattering (SANS) using a combination of dimyristoyl, phosphocholine (DMPC) and partially deuterated cholesterol (cholesterol-d7) with and without A β. We compare the results using grazing incidence and transmission SANS on lipid bilayer films and unilamellar vesicles respectively. The structural details on vesicles and bilayers work in conjunction with the circular dichroism on peptide in solution and oriented circular dichroism in bilayer films. The studies confirm a positive association of A β with the membrane layers. The results from different studies will be compared and contrasted in presentation.

  3. Effect of Daxx on cholesterol accumulation in hepatic cells

    Institute of Scientific and Technical Information of China (English)

    Qin-Hui Tuo; Lei Liang; Bing-Yang Zhu; Xuan Cao; Duan-Fang Liao

    2008-01-01

    AIM: To study the effect of Daxx on cholesterol accumulation in hepatic cells. METHODS: Sprague Dawley (SD) rats were fed a normal or high fat diet for 6 wk, and serum lipids and Daxx expression of hepatic tissues were measured by immunoblot assays. HepG2 cells were transfected with the pEGFP-C1/Daxx or pEGFP-C1 plasmid. Cells stably transfected with Daxx were identified by RT- PCR analysis. Total cholesterol levels were determined by high performance liquid chromatography. Activated- SREBP and caveolin-1 were assayed by western blotting. RESULTS: Hepatic Daxx protein was higher in normal rats than in high fat diet-fed rats. Noticeable negative correlations were seen between Daxx and LDL-C (7 = -7.56, P = 0.018), and between Daxx and TC (y = -9.07, P = 0.01), respectively. The total cholesterol of HepG2/GFP-Daxx cells was lower than that of control cells or HepG2/GFP cells (9.28 ± 0.19 vs 14.36 ± 4.45 or 13.94 ± 2.62, both P < 0.05). Furthermore, in HepG2/GFP cells, the expression of activated SREBP was lower than that ofcontrol cells, whereas caveolin-1 expression was higher. CONCLUSION: Overexpression of Daxx in HepG2 cells decreased intracellular cholesterol accumulation, which might be associated with inhibition of SREBP activity and an increase in caveolin-1 expression.

  4. Hearing Outcomes after Surgical Drainage of Petrous Apex Cholesterol Granuloma.

    Science.gov (United States)

    Rihani, Jordan; Kutz, J Walter; Isaacson, Brandon

    2015-06-01

    Objective This study aims to assess the hearing outcomes of patients undergoing surgical management of petrous apex cholesterol granuloma and to discuss the role of otic capsule-sparing approaches in drainage of petrous apex cholesterol granulomas. Design Retrospective case series. Setting Tertiary care medical center. Participants Eight patients underwent surgery for presumed or definitive cholesterol granuloma between 2002 and 2011 and met the inclusion criteria for this study. Main Outcome Measures Pre- and postoperative audiogram results as measured by pure tone thresholds and word recognition scores. Results Four patients (50%) demonstrated improvement in speech discrimination. One patient had an increase from 0 to 67% in word recognition scores. Four patients (50%) demonstrated worsening of pure tone thresholds, including two patients with anacusis. Conclusion Perilabyrinthine drainage of petrous apex cholesterol granulomas may result in hearing preservation or hearing improvement, even in the setting of otic capsule erosion. Patients should be counseled about the potential risk of significant hearing loss. PMID:26225297

  5. The effect of hyperthyroidism on serum cholesterol in Sudanese females

    International Nuclear Information System (INIS)

    This study was done, essentially to assess the effect of hyperthyroidism on lipid metabolism, respectively on total cholesterol in Sudanese females. Samples were collected from the referred patients to RIA lab in Sudan Atomic Energy Commission (SAEC). Ninety eight subjects were selected as study group. 48 hyperthyroid females age range (18-60) years in addition 50 euthyroid specimens were collected from females (of the same ages range) and used as control. Thyroid hormones, thyroxine (T4) and Triiodothyronine (T3), the thyroid stimulating hormone (TSH), and serum total cholestrol were measured for all subjects. Statistical analysis was done using SPSS computer program to compare the mean of cholesterol levels the control with the study group. The result showed that the significantly (P < 0.01). High levels of thyroid hormones in patients were accompanied by significantly (P< 0.01) decreased cholesterol levels. When this finding was compared in the control group serum total cholesterol levels kept the normal rang with the normal thyroid function.(Author)

  6. Lecithin:cholesterol acyltransferase-mediated modification of discoidal peripheral lymph high density lipoproteins: possible mechanism of formation of cholesterol-induced high density lipoproteins (HDLc) in cholesterol-fed dogs.

    OpenAIRE

    Dory, L; Sloop, C H; Boquet, L M; Hamilton, R L; Roheim, P S

    1983-01-01

    Peripheral lymph high density lipoproteins (HDL) of the cholesterol-fed dog differ in a number of characteristics from plasma HDL of the same animal. Their high content of free cholesterol, phospholipid, apoprotein E, and apoprotein A-IV, their greater heterogeneity in size, and the presence of many discoidal particles suggest that a portion of lymph HDL is assembled within the interstitial fluid. The present experiments demonstrate that the endogenous lecithin:cholesterol acyltransferase (LC...

  7. Characteristics of mRNA levels of hepatic key enzymes in cholesterol metabolism of genetically gallstone-susceptible mice

    Institute of Scientific and Technical Information of China (English)

    许国强; 赵力

    2004-01-01

    @@ Our previous study1 indicated that biliary cholesterol hypersecretion was the key pathophysiological defect of gallstone formation. Lith genes determine biliary cholesterol hypersecretion and susceptibility to cholesterol gallstone formation in C57L mice.

  8. 12-[(5-Iodo-4-azido-2-hydroxybenzoyl)amino]dodecanoic acid: Biological recognition by cholesterol esterase and acyl-CoA:cholesterol O-acyltransferase

    International Nuclear Information System (INIS)

    Potential probes of protein cholesterol and fatty acid binding sites, namely, 12-[(5-iodo-4-azido-2-hydroxybenzoyl)amino]dodecanoate (IFA) and its coenzyme A (IFA:CoA) and cholesteryl (IFA:CEA) esters, were synthesized. These radioactive, photoreactive lipid analogues were recognized as substrates and inhibitors of acyl-CoA;cholesterol O-acyltransferase (ACAT) and cholesterol esterase, neutral lipid binding enzymes which are key elements in the regulation of cellular cholesterol metabolism. In the dark, IFA reversibly inhibited cholesteryl [14C]oleate hydrolysis by purified bovine pancreatic cholesterol esterase with an apparent Ki of 150 μM. Cholesterol esterase inhibition by IFA became irreversible after photolysis with UV light and oleic acid provided 50% protection against inactivation. Incubation of homogeneous bovine pancreatic cholesterol esterase with IFA:CEA resulted in its hydrolysis to IFA and cholesterol, indicating recognition of IFA:CEA as a substrate by cholesterol esterase. The coenzyme A ester, IFA:CoA, was a reversible inhibitor of microsomal ACAT activity under dark conditions, and photolysis resulted in irreversible inhibition of enzyme activity with 87% efficiency. IFA:CoA was also recognized as a substrate by both liver and aortic microsomal ACATs, with resultant synthesis of 125IFA:CEA. IFA and its derivatives, IFA:CEA and IFA:CoA, are thus inhibitors and substrates for cholesterol esterase and ACAT. Biological recognition of these photoaffinity lipid analogues will facilitate the identification and structural analysis of hitherto uncharacterized protein lipid binding sites

  9. Influence of cholesterol and ceramide VI on the structure of multilamellar lipid membranes at water exchange

    International Nuclear Information System (INIS)

    The structural changes in the multilamellar lipid membranes of dipalmitoylphosphatidylcholine (DPPC)/cholesterol and DPPC/ceramide VI binary systems during hydration and dehydration have been studied by neutron diffraction. The effect of cholesterol and ceramide on the kinetics of water exchange in DPPC membranes is characterized. Compared to pure DPPC, membranes of binary systems swell faster during hydration (with a characteristic time of ∼30 min). Both compounds, ceramide VI and cholesterol, similarly affect the hydration of DPPC membranes, increasing the repeat distance due to the bilayer growth. However, in contrast to cholesterol, ceramide significantly reduces the thickness of the membrane water layer. The introduction of cholesterol into a DPPC membrane slows down the change in the parameters of the bilayer internal structure during dehydration. In the DPPC/ceramide VI/cholesterol ternary system (with a molar cholesterol concentration of 40%), cholesterol is partially released from the lamellar membrane structure into the crystalline phase.

  10. Cholesterol granuloma of a Haller cell associated with unilateral exophthalmos and diplopia.

    Science.gov (United States)

    Lee, Dong Hoon; Yoon, Tae Mi; Lee, Joon Kyoo; Lim, Sang Chul

    2016-09-01

    Cholesterol granuloma is rare in the paranasal sinuses. We present what is to our knowledge the first case of cholesterol granuloma of a Haller cell associated with unilateral exophthalmos and diplopia in a 55-year-old man. PMID:26719083

  11. Cholesterol Levels: What You Need to Know | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... in families. Lowering Cholesterol Using Therapeutic Lifestyle Changes (TLC) TLC is a set of lifestyle changes you ... cholesterol. The main parts of TLC are: The TLC Diet. The TLC Diet. This is a low- ...

  12. Characteristics associated with compliance to cholesterol lowering eating patterns.

    Science.gov (United States)

    Caggiula, A W; Watson, J E

    1992-02-01

    The achievement of high levels of adherence is the most important objective of nutrition intervention programs. In order to determine characteristics which were most highly related to adherence to a cholesterol lowering eating pattern, a group of 264 men were sampled. Participants had been enrolled for six years in a multi-risk reduction program for cardiovascular disease which included dietary intervention for blood cholesterol. They were asked to respond to 35 statements, each of which was designed to reflect one of seven characteristics: perception of threat of disease, cost-benefit of therapy, quality of care, social support, external environmental media, and internal as well as external health locus of control. There were seven possible responses to each statement, from strongly agree to strongly disagree. Using a reduced rank regression analysis the numerical answers to the items were treated as a set of predictors for the criterion measure, the food record rating (FRR) score which reflected compliance to a cholesterol lowering eating pattern. Overall the seven characteristics accounted for almost half of the variance in the FRR score (multiple R = 0.48). The most highly related characteristics were cost-benefit, quality of care and external environmental media. These results are highly consistent with those obtained in another population, and indicate the importance of minimizing the cost and increasing the benefits of cholesterol lowering programs by providing high quality treatment programs which emphasize tailoring the regimen to the individual. These results also support the importance of public information efforts such as the National Cholesterol Education Program. PMID:1298947

  13. Specific Cellular Incorporation of a Pyrene-Labelled Cholesterol: Lipoprotein-Mediated Delivery toward Ordered Intracellular Membranes

    OpenAIRE

    Gérald Gaibelet; Sophie Allart; François Tercé; Vincent Azalbert; Justine Bertrand-Michel; Safouane Hamdi; Xavier Collet; Stéphane Orlowski

    2015-01-01

    In the aim of testing tools for tracing cell trafficking of exogenous cholesterol, two fluorescent derivatives of cholesterol, 22-nitrobenzoxadiazole-cholesterol (NBD-Chol) and 21-methylpyrenyl-cholesterol (Pyr-met-Chol), with distinctive chemico-physical characteristics, have been compared for their cell incorporation properties, using two cell models differently handling cholesterol, with two incorporation routes. In the Caco-2 cell model, the cholesterol probes were delivered in bile salt ...

  14. Australian consumers' willingness to pay and willingness to purchase a hypothetical lower cholesterol pork product

    OpenAIRE

    Bellhouse, Amy; Malcolm, Bill; Griffith, Garry R.; Dunshea, Frank

    2010-01-01

    This study investigated whether there would be an increase in consumer willingness to pay and purchase if reduced cholesterol pork was introduced to the Australian market. A stated choice analysis was used, with the following questions addressed. How are current purchases of fresh pork affected by concerns about cholesterol content? What financial premium, if any, would consumers place on reduced cholesterol pork? Would consumers buy more pork if a low cholesterol option were available? Is th...

  15. A public health approach to cholesterol. Confronting the 'TV-auto-supermarket society'.

    OpenAIRE

    Bodenheimer, T

    1991-01-01

    Coronary heart disease has been proved to be associated with a "high-risk" diet and with elevated blood cholesterol levels. The National Cholesterol Education Program has embarked on a campaign based on intensive medical treatment of 60 million Americans with high blood cholesterol levels, but the degree of benefit of dietary change or pharmaceutical intervention or both to reduce blood cholesterol values remains a subject of disagreement within the scientific community. Evidence from compara...

  16. Helicobacter pylori lipopolysaccharide modification, Lewis antigen expression, and gastric colonization are cholesterol-dependent

    OpenAIRE

    McGee David J; Hildebrandt Ellen

    2009-01-01

    Abstract Background Helicobacter pylori specifically takes up cholesterol and incorporates it into the bacterial membrane, yet little is currently known about cholesterol's physiological roles. We compared phenotypes and in vivo colonization ability of H. pylori grown in a defined, serum-free growth medium, F12 with 1 mg/ml albumin containing 0 to 50 μg/ml cholesterol. Results While doubling times were largely unaffected by cholesterol, other overt phenotypic changes were observed. H. pylori ...

  17. Improved Coarse-Grained Modeling of Cholesterol-Containing Lipid Bilayers

    Science.gov (United States)

    2015-01-01

    Cholesterol trafficking, which is an essential function in mammalian cells, is intimately connected to molecular-scale interactions through cholesterol modulation of membrane structure and dynamics and interaction with membrane receptors. Since these effects of cholesterol occur on micro- to millisecond time scales, it is essential to develop accurate coarse-grained simulation models that can reach these time scales. Cholesterol has been shown experimentally to thicken the membrane and increase phospholipid tail order between 0 and 40% cholesterol, above which these effects plateau or slightly decrease. Here, we showed that the published MARTINI coarse-grained force-field for phospholipid (POPC) and cholesterol fails to capture these effects. Using reference atomistic simulations, we systematically modified POPC and cholesterol bonded parameters in MARTINI to improve its performance. We showed that the corrections to pseudobond angles between glycerol and the lipid tails and around the oleoyl double bond particle (the “angle-corrected model”) slightly improves the agreement of MARTINI with experimentally measured thermal, elastic, and dynamic properties of POPC membranes. The angle-corrected model improves prediction of the thickening and ordering effects up to 40% cholesterol but overestimates these effects at higher cholesterol concentration. In accordance with prior work that showed the cholesterol rough face methyl groups are important for limiting cholesterol self-association, we revised the coarse-grained representation of these methyl groups to better match cholesterol-cholesterol radial distribution functions from atomistic simulations. In addition, by using a finer-grained representation of the branched cholesterol tail than MARTINI, we improved predictions of lipid tail order and bilayer thickness across a wide range of concentrations. Finally, transferability testing shows that a model incorporating our revised parameters into DOPC outperforms other

  18. Apolipoprotein E gene polymorphism influences aggressive behavior in prostate cancer cells by deregulating cholesterol homeostasis

    OpenAIRE

    IFERE, GODWIN O.; Desmond, Renee; Demark-Wahnefried, Wendy; Nagy, Tim R.

    2013-01-01

    High circulating cholesterol and its deregulated homeostasis may facilitate prostate cancer progression. Genetic polymorphism in Apolipoprotein (Apo) E, a key cholesterol regulatory protein may effect changes in systemic cholesterol levels. In this investigation, we determined whether variants of the Apo E gene can trigger defective intracellular cholesterol efflux, which could promote aggressive prostate cancer. ApoE genotypes of weakly (non-aggressive), moderate and highly tumorigenic (aggr...

  19. Exosome Secretion Ameliorates Lysosomal Storage of Cholesterol in Niemann-Pick Type C Disease*

    OpenAIRE

    STRAUSS, K; C. GOEBEL; Runz, H.; Mobius, W.; Weiss, S; Feussner, I.; M. Simons; A. Schneider

    2010-01-01

    Niemann-Pick type C1 disease is an autosomal-recessive lysosomal storage disorder. Loss of function of the npc1 gene leads to abnormal accumulation of free cholesterol and sphingolipids within the late endosomal and lysosomal compartments resulting in progressive neurodegeneration and dysmyelination. Here, we show that oligodendroglial cells secrete cholesterol by exosomes when challenged with cholesterol or U18666A, which induces late endosomal cholesterol accumulation. Up-regulation of exos...

  20. Concentration-dependent Diversification Effects of Free Cholesterol Loading on Macrophage Viability and Polarization

    OpenAIRE

    Xu, Xiaoyang; Zhang, Aolin; Li, Ningjun; Li, Pin-Lan; Zhang, Fan

    2015-01-01

    The accumulation of free cholesterol in atherosclerotic lesions has been well documented in both animals and humans. In studying the relevance of free cholesterol buildup in atherosclerosis, contradictory results have been generated, indicating that free cholesterol produces both pro- and anti-atherosclerosis effects in macrophages. This inconsistency might stem from the examination of only select concentrations of free cholesterol. In the present study, we sought to investigate the implicati...

  1. Studies on cholesterol and bile acid metabolism in relation to plasma lipoproteins

    OpenAIRE

    Sjöberg, Beatrice

    2016-01-01

    The metabolism of cholesterol and bile acids is tightly controlled but only partially characterized. The liver is responsible for most of the clearance and catabolism of plasma cholesterol, and the hepatocyte expression of LDL receptors is central in this process. The major pathways for net excretion of cholesterol from the body are through biliary excretion as free cholesterol or after conversion to bile acids. Through activation of the nuclear receptor FXR and the G protein-coupled receptor...

  2. The Role of Nutrition and Physical Activity in Cholesterol and Aging.

    Science.gov (United States)

    Ribeiro, Sandra Maria Lima; Luz, Silmara Dos Santos; Aquino, Rita de Cássia

    2015-08-01

    Cholesterol is a precursor of several substances with important biologic activities; however, it is common to associate this molecule only with bad outcomes. This article reviews the cholesterol metabolism, its functions in the human body, its pathogenicity, and its elimination. The modifications in biochemical paths of cholesterol in aging are highlighted. Finally, the role of diet, physical activity, and exercise in cholesterol management is discussed. PMID:26195099

  3. Animal model of high cholesterol atherosclerotic erectile dysfunction and mechanism of atherosclerotic erectile dysfunction

    Institute of Scientific and Technical Information of China (English)

    Guo-ShengYang; Zhao-DianChen; Hong-JuWang

    2004-01-01

    Aim: To establish the animal model of atherosclerotic erectile dysfunction (ED) induced by high cholesterol diet and explore the mechanism of atherosclerotic ED. Methods: Thirty male rabbits were divided at random into two groups: the normal diet (ND)group (n=10) and the high cholesterol (HCH) group fed with 1.5% cholesterol diet (n=20). Serum total cholesterol, plaque areas of the ascending aorta,

  4. Relation of cholesterol metabolism to pediatric gallstone disease: a retrospective controlled study

    OpenAIRE

    Koivusalo, Antti; Pakarinen, Mikko; Gylling, Helena; Nissinen, Markku J

    2015-01-01

    Background Cholesterol metabolism may be involved in pediatric gallstone disease. We aimed to reveal cholesterol metabolites and phytosterols and their relation to stone composition of sterols in children having black pigment and cholesterol stones. Methods We performed retrospective controlled clinical study, in which we examined parameters of cholesterol metabolism and liver function values in serum (n = 28) and gallstones (n = 46) of consecutively cholecystectomized children. Serum values ...

  5. Methanol Leaf Extract of Persea americana Protects Rats against Cholesterol-Induced Hyperlipidemia

    OpenAIRE

    Kolawole, O. T.; Kolawole, S. O.; Ayankunle, A. A.; Olaniran, I. O.

    2012-01-01

    Aim: To investigate anti-hyperlipidemic activity of methanol leaf extract of Persea americana (MEPA) in cholesterol-induced hyperlipidemic rats. Methodology: The animals were randomly divided into five groups of 5 rats each. Group1 served as the normal control (NC) and received distilled water. Group 2, the cholesterol-induced hyperlipidemic control (CHOL) was given cholesterol diet (20% groundnut oil, 1% cholesterol and 0.5% cholic acid mixed with rat pellet) orally. Groups 3 and 4 received ...

  6. Better risk assessment with glycated hemoglobin instead of cholesterol in CVD risk prediction charts

    OpenAIRE

    Faeh, David; Rohrmann, Sabine; Braun, Julia

    2013-01-01

    Traditional risk charts for the prediction of cardiovascular disease (CVD) include cholesterol parameters. We evaluated how models predict fatal CVD when cholesterol is replaced by glucose parameters. We used data from NHANES III, a US survey conducted 1988-1994 (follow-up until 2006); 15,454 participants (1,716 CVD deaths) were included. Based on the ESC SCORE method, we used age, sex, blood pressure, smoking and either of the following: (1) total cholesterol, (2) total-to-HDL-cholesterol, (...

  7. Cholesterol as a Causative Factor in Alzheimer Disease: A Debatable Hypothesis

    OpenAIRE

    Wood, W. Gibson; Li, Ling; Müller, Walter E.; Eckert, Gunter P.

    2014-01-01

    High serum/plasma cholesterol levels have been suggested as a risk factor for Alzheimer disease (AD). Some reports, mostly retrospective epidemiological studies, have observed a decreased prevalence of AD in patients taking the cholesterol lowering drugs, statins. The strongest evidence causally linking cholesterol to AD is provided by experimental studies showing that adding/reducing cholesterol alters amyloid precursor protein (APP) and amyloid beta-protein (Aβ) levels. However, there are p...

  8. Cholesterol, Atherosclerosis and Coronary Disease in the UK, 1950–2000, vol. 27.

    OpenAIRE

    2006-01-01

    Cholesterol began to be accepted after the Second World War as a significant cause of atherosclerosis and associated conditions such as coronary heart disease (CHD). This Witness Seminar, chaired by Professor Michael Oliver, included a discussion of the basic research on cholesterol. Moving on, early epidemiological studies demonstrated the relationship between excess saturated fat consumption and elevated levels of cholesterol, although cholesterol alone did not explain all population differ...

  9. Fabricating an Amperometric Cholesterol Biosensor by a Covalent Linkage between Poly(3-thiopheneacetic acid and Cholesterol Oxidase

    Directory of Open Access Journals (Sweden)

    Kuo-Chuan Ho

    2009-03-01

    Full Text Available In this study, use of the covalent enzyme immobilization method was proposed to attach cholesterol oxidase (ChO on a conducting polymer, poly(3-thiopheneacetic acid, [poly(3-TPAA]. Three red-orange poly(3-TPAA films, named electrodes A, B and C, were electropolymerized on a platinum electrode by applying a constant current of 1.5 mA, for 5, 20 and 100 s, respectively. Further, 1-ethyl-3-(3-dimethylamiopropylcarbodiimide hydrochloride (EDC‧HCl and N-hydroxysuccinimide (NHS were used to activate the free carboxylic groups of the conducting polymer. Afterwards, the amino groups of the cholesterol oxidase were linked on the activated groups to form peptide bonds. The best sensitivity obtained for electrode B is 4.49 mA M-1 cm-2,with a linear concentration ranging from 0 to 8 mM, which is suitable for the analysis of cholesterol in humans. The response time (t95 is between 70 and 90 s and the limit of detection is 0.42 mM, based on the signal to noise ratio equal to 3. The interference of species such as ascorbic acid and uric acid increased to 5.2 and 10.3% of the original current response, respectively, based on the current response of cholesterol (100%. With respect to the long-term stability, the sensing response retains 88% of the original current after 13 days.

  10. Caveolae and Caveolin-1 Integrate Reverse Cholesterol Transport and Inflammation in Atherosclerosis.

    Science.gov (United States)

    Qin, Li; Zhu, Neng; Ao, Bao-Xue; Liu, Chan; Shi, Ya-Ning; Du, Ke; Chen, Jian-Xiong; Zheng, Xi-Long; Liao, Duan-Fang

    2016-01-01

    Lipid disorder and inflammation play critical roles in the development of atherosclerosis. Reverse cholesterol transport is a key event in lipid metabolism. Caveolae and caveolin-1 are in the center stage of cholesterol transportation and inflammation in macrophages. Here, we propose that reverse cholesterol transport and inflammation in atherosclerosis can be integrated by caveolae and caveolin-1. PMID:27011179

  11. Caveolae and Caveolin-1 Integrate Reverse Cholesterol Transport and Inflammation in Atherosclerosis

    OpenAIRE

    Li Qin; Neng Zhu; Bao-Xue Ao; Chan Liu; Ya-Ning Shi; Ke Du; Jian-Xiong Chen; Xi-Long Zheng; Duan-Fang Liao

    2016-01-01

    Lipid disorder and inflammation play critical roles in the development of atherosclerosis. Reverse cholesterol transport is a key event in lipid metabolism. Caveolae and caveolin-1 are in the center stage of cholesterol transportation and inflammation in macrophages. Here, we propose that reverse cholesterol transport and inflammation in atherosclerosis can be integrated by caveolae and caveolin-1.

  12. Caveolae and Caveolin-1 Integrate Reverse Cholesterol Transport and Inflammation in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Li Qin

    2016-03-01

    Full Text Available Lipid disorder and inflammation play critical roles in the development of atherosclerosis. Reverse cholesterol transport is a key event in lipid metabolism. Caveolae and caveolin-1 are in the center stage of cholesterol transportation and inflammation in macrophages. Here, we propose that reverse cholesterol transport and inflammation in atherosclerosis can be integrated by caveolae and caveolin-1.

  13. Effect of a Konjac flour diet on the endogenous cholesterol metabolism in rats

    International Nuclear Information System (INIS)

    The influence of Konjac flour (KF), crude Konjac mannan prepared from the tubers of Amorphophallus Konjac K. Koch (Araceae), on the endogenous cholesterol metabolism in rats was studied. 1) The high levels of serum and liver cholesterol in the rats preliminary fed a hypercholesterolemic diet containing 1% cholesterol and 0.25% bile acids for 10 days were reduced to normal by changing that diet to cholesterol-free diets supplemented with or without KF, and their reduction rates were especially stimulated when shifted to a cholesterol-free diet with 5% KF. 2) The in vivo and in vitro incorporations of acetate-2-14C into liver cholesterol and the in vivo degradation of cholesterol-26-14C to the expired CO2 in rats fed a cholesterol-free, KF diet for 10 days were examined. The biosynthesis of cholesterol was substantially higher in the KF diet groups in vivo and in vitro than the control diet group, while degradation was not accelerated by the administration of KF. However, no significant alterations in the levels of both serum and liver cholesterol were shown in rats fed the KF diet as compared with the control group. 3) From these results, KF is inferred to stimulate the excretion of the undergraded liver cholesterol into bile, or subsequently into feces. Possible roles of the hypocholesterolemic activity of KF in relation to the intestinal reabsorption of endogenous enterohepatic circulating cholesterol or bile acids were also discussed. (auth.)

  14. A physiologically based in silico kinetic model predicting plasma cholesterol concentrations in humans[S

    Science.gov (United States)

    van de Pas, Niek C. A.; Woutersen, Ruud A.; van Ommen, Ben; Rietjens, Ivonne M. C. M.; de Graaf, Albert A.

    2012-01-01

    Increased plasma cholesterol concentration is associated with increased risk of cardiovascular disease. This study describes the development, validation, and analysis of a physiologically based kinetic (PBK) model for the prediction of plasma cholesterol concentrations in humans. This model was directly adapted from a PBK model for mice by incorporation of the reaction catalyzed by cholesterol ester transfer protein and contained 21 biochemical reactions and eight different cholesterol pools. The model was calibrated using published data for humans and validated by comparing model predictions on plasma cholesterol levels of subjects with 10 different genetic mutations (including familial hypercholesterolemia and Smith-Lemli-Opitz syndrome) with experimental data. Average model predictions on total cholesterol were accurate within 36% of the experimental data, which was within the experimental margin. Sensitivity analysis of the model indicated that the HDL cholesterol (HDL-C) concentration was mainly dependent on hepatic transport of cholesterol to HDL, cholesterol ester transfer from HDL to non-HDL, and hepatic uptake of cholesterol from non-HDL-C. Thus, the presented PBK model is a valid tool to predict the effect of genetic mutations on cholesterol concentrations, opening the way for future studies on the effect of different drugs on cholesterol levels in various subpopulations in silico. PMID:23024287

  15. A physiologically based in silico kinetic model predicting plasma cholesterol concentrations in humans.

    Science.gov (United States)

    van de Pas, Niek C A; Woutersen, Ruud A; van Ommen, Ben; Rietjens, Ivonne M C M; de Graaf, Albert A

    2012-12-01

    Increased plasma cholesterol concentration is associated with increased risk of cardiovascular disease. This study describes the development, validation, and analysis of a physiologically based kinetic (PBK) model for the prediction of plasma cholesterol concentrations in humans. This model was directly adapted from a PBK model for mice by incorporation of the reaction catalyzed by cholesterol ester transfer protein and contained 21 biochemical reactions and eight different cholesterol pools. The model was calibrated using published data for humans and validated by comparing model predictions on plasma cholesterol levels of subjects with 10 different genetic mutations (including familial hypercholesterolemia and Smith-Lemli-Opitz syndrome) with experimental data. Average model predictions on total cholesterol were accurate within 36% of the experimental data, which was within the experimental margin. Sensitivity analysis of the model indicated that the HDL cholesterol (HDL-C) concentration was mainly dependent on hepatic transport of cholesterol to HDL, cholesterol ester transfer from HDL to non-HDL, and hepatic uptake of cholesterol from non-HDL-C. Thus, the presented PBK model is a valid tool to predict the effect of genetic mutations on cholesterol concentrations, opening the way for future studies on the effect of different drugs on cholesterol levels in various subpopulations in silico. PMID:23024287

  16. Extreme nonfasting remnant cholesterol vs extreme LDL cholesterol as contributors to cardiovascular disease and all-cause mortality in 90000 individuals from the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Freiberg, Jacob J; Nordestgaard, Børge G

    2015-01-01

    BACKGROUND: Increased nonfasting remnant cholesterol, like increased LDL cholesterol, is causally associated with increased risk for ischemic heart disease (IHD). We tested the hypothesis that extreme concentrations of nonfasting remnant and LDL cholesterol are equal contributors to the risk of IHD......, myocardial infarction (MI), and all-cause mortality. METHODS: We compared stepwise increasing concentrations of nonfasting remnant and LDL cholesterol for association with risk of IHD, MI, and all-cause mortality in approximately 90 000 individuals from the Danish general population. During up to 22 years of...... complete follow-up, 4435 participants developed IHD, 1722 developed MI, and 8121 died. RESULTS: Compared with participants with nonfasting remnant cholesterol <0.5 mmol/L (19.3 mg/dL), hazard ratios for IHD ranged from 1.3 (95% CI 1.1-1.5) for remnant cholesterol of 0.5-0.99 mmol/L (19.3-38.2 mg/dL) to 2...

  17. FLIM studies of 22- and 25-NBD-cholesterol in living HEK293 cells: Plasma membrane change induced by cholesterol depletion

    Czech Academy of Sciences Publication Activity Database

    Ostašov, Pavel; Sýkora, Jan; Brejchová, Jana; Olžyńska, Agnieszka; Hof, Martin; Svoboda, Petr

    167-168, FEB-MAR (2013), s. 62-69. ISSN 0009-3084 R&D Projects: GA ČR(CZ) GAP207/12/0919 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 ; RVO:61388955 Keywords : cholesterol depletion * beta- Cyclodextrin * 22-NBD-cholesterol * 25-NBD-cholesterol * FLIM studies * intact HEK293 cells Subject RIV: CE - Biochemistry; CF - Physical ; Theoretical Chemistry (UFCH-W) Impact factor: 2.593, year: 2013

  18. Reusable and Mediator-Free Cholesterol Biosensor Based on Cholesterol Oxidase Immobilized onto TGA-SAM Modified Smart Bio-Chips

    OpenAIRE

    Rahman, Mohammed M.

    2014-01-01

    A reusable and mediator-free cholesterol biosensor based on cholesterol oxidase (ChOx) was fabricated based on self-assembled monolayer (SAM) of thioglycolic acid (TGA) (covalent enzyme immobilization by dropping method) using bio-chips. Cholesterol was detected with modified bio-chip (Gold/Thioglycolic-acid/Cholesterol-oxidase i.e., Au/TGA/ChOx) by reliable cyclic voltammetric (CV) technique at room conditions. The Au/TGA/ChOx modified bio-chip sensor demonstrates good linearity (1.0 nM to 1...

  19. Reasons for the upsetting cholesterol level during the community investigation from residents, physicians, and social aspects: The China Cholesterol Education Program (CCEP)

    Institute of Scientific and Technical Information of China (English)

    XIE Jiang; GUAN Fei; WANG Jia-hong; HU Da-yi

    2011-01-01

    Background The community medical center is the first barrier for lipid control. We aimed to survey the residents' cholesterol condition in the community, and pursue the reasons for the upsetting results from various aspects.Methods Residents and physicians were recruited from four community centers. Residents completed questionnaires and a physical examination as well as biochemical analysis. Physicians were also asked to complete a questionnaire,some of which were about basic knowledge of lipids.Results About 37.0% male and 48.1% female had elevated cholesterol levels. Residents' blood pressure (BP), fasting glucose (FG), body mass index (BMI), and waist circumference (WC) were positively associated with their low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Framingham risk scoring (FRS) was strongly related to cholesterol (P <0.001 for LDL-C and TC). Residents' higher education grade was positively related to a normal cholesterol condition (P<0.001), while personal income was negatively related to it. Rural residents had higher percent of population with normal cholesterol level (normal cholesterol rate) than their city counterpart (P <0.001). Although physicians with college education had a much higher lipid knowledge level themselves, the physicians' factors had almost no relationship with the residents' cholesterol levels.Conclusions Management of hypercholesterolemia should be an important component of health strategy in Beijing.Education is imperative for residents as well as for physicians.

  20. The Utilization of Seaweed as a Source of Dietary Fiber to Decrease the Serum Cholesterol in Rats

    Directory of Open Access Journals (Sweden)

    MADE ASTAWAN

    2005-03-01

    Full Text Available The cholesterol lowering effect of seaweed (Eucheuma cottonii powder as a source of dietary fiber was evaluated in hypercholesterolemic rats. Four groups of five male Sprague Dawley hypercholesterolemic rats were fed a 0% cholesterol-0% seaweed powder (negative control; 1% cholesterol-5% seaweed powder; 1% cholesterol-10% seaweed powder; and 1% cholesterol-0% seaweed powder (positive control for 35 days. Seaweed powder contained feed did not affect the growth of rats but significantly lowered the serum total cholesterol, LDL cholesterol, triglyceride, and atherogenic index. The lowest serum cholesterol was found in the hypercholesterolemic rats fed with 1% cholesterol-10% seaweed powder. The values of total-cholesterol, LDL-cholesterol, and triglyceride were 67.7, 33.0, and 47.3 mg/dl, respectively.

  1. The Fruit Fly Drosophila melanogaster as a Model System to Study Cholesterol Metabolism and Homeostasis

    Directory of Open Access Journals (Sweden)

    Ryusuke Niwa

    2011-01-01

    Full Text Available Cholesterol has long been recognized for its versatile roles in influencing the biophysical properties of cell membranes and for serving as a precursor of steroid hormones. While many aspects of cholesterol biosynthesis are well understood, little is currently known about the molecular mechanisms of cholesterol metabolism and homeostasis. Recently, genetic approaches in the fruit fly, Drosophila melanogaster, have been successfully used for the analysis of molecular mechanisms that regulate cholesterol metabolism and homeostasis. This paper summarizes the recent studies on genes that regulate cholesterol metabolism and homeostasis, including neverland, Niemann Pick type C(NPC disease genes, and DHR96.

  2. Stanol esters attenuate the aggravating effect of dietary cholesterol on atherosclerosis in homozygous Watanabe rabbits

    DEFF Research Database (Denmark)

    Schrøder, Malene; Husche, Constanze; Pilegaard, Kirsten; Lütjohann, Dieter; Mortensen, Alicja

    2009-01-01

    Plant stanols are marketed as natural means to lower blood cholesterol in humans; hence the effect on combined familial hyperlipidemia is not known. The objective was to investigate the effect of stanol esters on blood lipids and aortic atherosclerosis in homozygous WHHL rabbits challenged with...... dietary cholesterol. A total of 36 rabbits, 6 weeks of age, with initial plasma cholesterol of 22.5 mmol/L were assigned to two treatment groups fed a standard rabbit chow with 1 g/kg cholesterol or this diet added 34 g/kg stanol ester, respectively, for 16 weeks. Plasma cholesterol was measured initially...

  3. Ileus caused by cholesterol crystal embolization: A case report.

    Science.gov (United States)

    Azuma, Shunjiro; Ikenouchi, Maiko; Akamatsu, Takuji; Seta, Takeshi; Urai, Shunji; Uenoyama, Yoshito; Yamashita, Yukitaka

    2016-03-28

    Cholesterol crystal embolization (CCE) is a rare systemic embolism caused by formation of cholesterol crystals from atherosclerotic plaques. CCE usually occurs during vascular manipulation, such as vascular surgery or endovascular catheter manipulation, or due to anticoagulation or thrombolytic therapy. We report a rare case of intestinal obstruction caused by spontaneous CCE. An 81-year-old man with a history of hypertension was admitted for complaints of abdominal pain, bloating, and anorexia persisting for 4 mo. An abdominal computed tomography revealed intestinal ileus. His symptoms were immediately relieved by an ileus tube insertion, and he was discharged 6 d later. However, these symptoms immediately reappeared and persisted, and partial resection of the small intestine was performed. A histopathological examination indicated that small intestine obstruction was caused by CCE. At the 12-mo follow-up, the patient showed no evidence of CCE recurrence. Thus, in cases of intestinal obstruction, CCE should also be considered. PMID:27022232

  4. Enriching membrane cholesterol improves stability and cryosurvival of buffalo spermatozoa.

    Science.gov (United States)

    Rajoriya, J S; Prasad, J K; Ramteke, S S; Perumal, P; Ghosh, S K; Singh, M; Pande, Megha; Srivastava, N

    2016-01-01

    Buffalo spermatozoa are comparatively more susceptible to freezing hazards than cattle spermatozoa. In recent times incubation of spermatozoa with cholesterol-loaded-cyclodextrins (CLC) has shown improvements in semen quality in several species. Therefore, this study was undertaken to evaluate the incubation level of CLC at which maximum benefit is derived for the buffalo spermatozoa. For the study, 120 million spermatozoa were incubated in 2, 3 and 4 mg/mL of CLC (Gr II, III and IV, respectively) and cholesterol and phospholipids content, their ratio, flow cytometric evaluation of plasma membrane integrity (PMI), plasma membrane fluidity and extent of cryoinjury (Chlortetracycline, CTC assay) were compared with an untreated control (Gr I). Additionally the ability of cholesterol-loaded-spermatozoa to undergo induced acrosome reaction (IAR) using ionophore calcium (A23187) was evaluated in frozen-thaw samples. Data show a significant and linear increase (CV=0.88) in cholesterol content of spermatozoa in Gr II, III and IV and a significant decrease in phospholipids content at frozen-thaw stage in Gr IV than Gr III spermatozoa. The study revealed a significant improvement in PMI and significant reduction in plasma membrane fluidity and cryoinjury of CLC treated spermatozoa at progressive stages in three groups compared to control. Nevertheless, spermatozoa of Gr II, III and IV were significantly less responsive to ionophore calcium (A23187) than Gr I. This study shows for the first time that incubation of buffalo bull spermatozoa with CLC (3mg/120×10(6)) prior to processing permits greater numbers of sperm to survive cryopreservation while allowing spermatozoa to capacitate and the acrosome to react to AR inducer ionophore calcium (A23187). PMID:26619942

  5. Maintaining cholesterol homeostasis:Sterol regulatory element-binding proteins

    Institute of Scientific and Technical Information of China (English)

    Lutz W. Weber; Meinrad Boll; Andreas Stampfl

    2004-01-01

    The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has become much more transparent with the discovery of sterol regulatory element binding proteins (SREBPs) in recent years. These membrane proteins are members of the basic helix-loop-helix-leucine zipper (bHLHZip) family of transcription factors. They activate the expression of at least 30 genes involved in the synthesis of cholesterol and lipids. SREBPs are synthesized as precursor proteins in the endoplasmic reticulum (ER), where they form a complex with another protein, SREBP cleavage activating protein (SCAP).The SCAP molecule contains a sterol sensory domain. In the presence of high cellular sterol concentrations SCAP confines SREBP to the ER. With low cellular concentrations, SCAP escorts SREBP to activation in the Golgi. There, SREBP undergoes two proteolytic cleavage steps to release the mature, biologically active transcription factor, nuclear SREBP (nSREBP). nSREBP translocates to the nucleus and binds to sterol response elements (SRE) in the promoter/enhancer regions of target genes. Additional transcription factors are required to activate transcription of these genes. Three different SREBPs are known, SREBPs-1a, -1c and -2. SREBP-1a and -1c are isoforms produced from a single gene by alternate splicing. SREBP-2is encoded by a different gene and does not display any isoforms. It appears that SREBPs alone, in the sequence described above, can exert complete control over cholesterol synthesis, whereas many additional factors (hormones,cytokines, etc.) are required for complete control of lipid metabolism. Medicinal manipulation of the SREBP/SCAP system is expected to prove highly beneficial in the management of cholesterol-related disease.

  6. Sensitized Photooxygenation of Cholesterol and Pseudocholesterol Derivatives via Singlet Oxygen

    Directory of Open Access Journals (Sweden)

    Zeng Daixun

    2001-01-01

    Full Text Available 3-Substituted cholesterols and 7-substituted pseudocholesterols undergo a facile photooxygenation sensitized by 9, 10-dicyanoanthracene (DCA and lumiflavin (LF to give similar, oppositely-positioned enol derivatives. Both steroids showed the same reaction pattern associated with the endocyclic 5- and 4-olefin units, respectively. The reaction was proposed to proceed via the ene reaction of singlet oxygen and subsequent rearrangement of the initially formed 5a-hydroperoxides.

  7. Electrochemistry of bile acids, cholesterol, and related compounds (an overview)

    OpenAIRE

    Pecková, Karolina; Nesměrák, Karel

    2012-01-01

    This review summarizes electrochemical methods used for the investigation, determination, and monitoring of bile acids and their conjugates, cholesterol, phytosterols, and related compounds. In electrochemistry-related research they do not belong among frequently studied compounds, because they are inactive under variety of conditions and electrode materials. The several examples of their redox activity include electrochemical reduction of bile acids at mercury electrodes and modified glassy ...

  8. The cholesterol-raising factor from coffee beans.

    OpenAIRE

    Urgert, R.; Katan, M B

    1996-01-01

    Coffee beans and some types of coffee brew - not the regular types of coffee prepared with a paper filter or with soluble coffee granules - contain the diterpenes cafestol and kahweol. Cafestol and kahweol raise the serum concentration of cholesterol and triglycerides in humans, and they also appear mildly to affect the integrity of liver cells. Both effects are transient after withdrawal of the diterpenes, and it is as yet unsure whether these effects are associated. Patients at increased ri...

  9. Skin tissue cholesterol is not related to vascular occlusive disease

    OpenAIRE

    Reiter, Markus; Wirth, Susan; Pourazim, Ali; Puchner, Stefan; Baghestanian, Mehrdad; Minar, Erich; Bucek, Robert A.

    2007-01-01

    Abstract The objective of the present study was to evaluate the role of skin tissue cholesterol (SkinTc) in predicting the presence of atherosclerosis. SkinTc concentrations were determined in 318 consecutive patients by using the non-invasive PREVU POC Skin Sterol Test. Additionally, a complete lipid status and cardiovascular risk profile according to the PROCAM and Framingham scores as well as an evaluation by carotid duplex sonography and ankle?brachial blood pressure index test...

  10. Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

    OpenAIRE

    Samia Hannaoui; Su Yeon Shim; Yo Ching Cheng; Erica Corda; Sabine Gilch

    2014-01-01

    Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI) anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinog...

  11. Hyperspectral imaging for detection of cholesterol in human skin

    Science.gov (United States)

    Milanič, Matija; Bjorgan, Asgeir; Larsson, Marcus; Marraccini, Paolo; Strömberg, Tomas; Randeberg, Lise L.

    2015-03-01

    Hypercholesterolemia is characterized by high levels of cholesterol in the blood and is associated with an increased risk of atherosclerosis and coronary heart disease. Early detection of hypercholesterolemia is necessary to prevent onset and progress of cardiovascular disease. Optical imaging techniques might have a potential for early diagnosis and monitoring of hypercholesterolemia. In this study, hyperspectral imaging was investigated for this application. The main aim of the study was to identify spectral and spatial characteristics that can aid identification of hypercholesterolemia in facial skin. The first part of the study involved a numerical simulation of human skin affected by hypercholesterolemia. A literature survey was performed to identify characteristic morphological and physiological parameters. Realistic models were prepared and Monte Carlo simulations were performed to obtain hyperspectral images. Based on the simulations optimal wavelength regions for differentiation between normal and cholesterol rich skin were identified. Minimum Noise Fraction transformation (MNF) was used for analysis. In the second part of the study, the simulations were verified by a clinical study involving volunteers with elevated and normal levels of cholesterol. The faces of the volunteers were scanned by a hyperspectral camera covering the spectral range between 400 nm and 720 nm, and characteristic spectral features of the affected skin were identified. Processing of the images was done after conversion to reflectance and masking of the images. The identified features were compared to the known cholesterol levels of the subjects. The results of this study demonstrate that hyperspectral imaging of facial skin can be a promising, rapid modality for detection of hypercholesterolemia.

  12. Effectiveness of altering serum cholesterol levels without drugs

    OpenAIRE

    Rosenthal, Robert L.

    2000-01-01

    Drug therapy with statins and other agents can result in dramatic lipidlowering effects. Despite the wealth of data supporting the beneficial effects of pharmacologic therapy on cardiovascular risk, patients often express a desire to accomplish similar goals with diet alone. And, except for patients with extreme cholesterol elevations, consensus panels all promote dietary therapy as an initial step in the treatment of hyperlipidemia. This review examines a variety of dietary strategies design...

  13. Dynamical modeling of the cholesterol regulatory pathway with Boolean networks

    OpenAIRE

    Corcos Laurent; Kervizic Gwenael

    2008-01-01

    Abstract Background Qualitative dynamics of small gene regulatory networks have been studied in quite some details both with synchronous and asynchronous analysis. However, both methods have their drawbacks: synchronous analysis leads to spurious attractors and asynchronous analysis lacks computational efficiency, which is a problem to simulate large networks. We addressed this question through the analysis of a major biosynthesis pathway. Indeed the cholesterol synthesis pathway plays a pivo...

  14. Ionic channels and nerve membrane constituents. Tetrodotoxin-like interaction of saxitoxin with cholesterol monolayers.

    Science.gov (United States)

    Villegas, R; Barnola, F V

    1972-01-01

    Saxitoxin (STX) and tetrodotoxin (TTX) have the same striking property of blocking the Na(+) channels in the axolemma. Experiments with nerve plasma membrane components of the squid Dosidicus gigas have shown that TTX interacts with cholesterol monolayers. Similar experiments were carried out with STX. The effect of STX on the surface pressure-area diagrams of lipid monolayers and on the fluorescence emission spectra of sonicated nerve membranes was studied. The results indicate a TTX-like interaction of STX with cholesterol monolayers. The expansion of the monolayers caused by 10(-6)M STX was 2.2 A(2)/cholesterol molecule at 25 degrees C. From surface pressure measurements at constant cholesterol area (39 A(2)/molecule) in media with various STX concentrations, it was calculated that the STX/cholesterol surface concentration ratio is 0.54. The apparent dissociation constant of the STX-cholesterol monolayer complex is 4.0 x 10(-7)M. The STX/cholesterol ratio and the apparent dissociation constant are similar to those determined for TTX. The presence of other lipids in the monolayers affects the STX-cholesterol association. The interactions of STX and TTX with cholesterol monolayers suggest (a) that cholesterol molecules may be part of the nerve membrane Na(+) channels, or (b) that the toxin receptor at the nerve membrane shares similar chemical features with the cholesterol monolayers. PMID:5007264

  15. Brain Cholesterol Metabolism and Its Defects: Linkage to Neurodegenerative Diseases and Synaptic Dysfunction.

    Science.gov (United States)

    Petrov, A M; Kasimov, M R; Zefirov, A L

    2016-01-01

    Cholesterol is an important constituent of cell membranes and plays a crucial role in the compartmentalization of the plasma membrane and signaling. Brain cholesterol accounts for a large proportion of the body's total cholesterol, existing in two pools: the plasma membranes of neurons and glial cells and the myelin membranes . Cholesterol has been recently shown to be important for synaptic transmission, and a link between cholesterol metabolism defects and neurodegenerative disorders is now recognized. Many neurodegenerative diseases are characterized by impaired cholesterol turnover in the brain. However, at which stage the cholesterol biosynthetic pathway is perturbed and how this contributes to pathogenesis remains unknown. Cognitive deficits and neurodegeneration may be associated with impaired synaptic transduction. Defects in cholesterol biosynthesis can trigger dysfunction of synaptic transmission. In this review, an overview of cholesterol turnover under physiological and pathological conditions is presented (Huntington's, Niemann-Pick type C diseases, Smith-Lemli-Opitz syndrome). We will discuss possible mechanisms by which cholesterol content in the plasma membrane influences synaptic processes. Changes in cholesterol metabolism in Alzheimer's disease, Parkinson's disease, and autistic disorders are beyond the scope of this review and will be summarized in our next paper. PMID:27099785

  16. Modeling of Mechanical Stress Exerted by Cholesterol Crystallization on Atherosclerotic Plaques

    Science.gov (United States)

    Cui, Dongyao; Yu, Xiaojun; Chen, Si; Liu, Xinyu; Tang, Hongying; Wang, Xianghong; Liu, Linbo

    2016-01-01

    Plaque rupture is the critical cause of cardiovascular thrombosis, but the detailed mechanisms are not fully understood. Recent studies have found abundant cholesterol crystals in ruptured plaques, and it has been proposed that the rapid expansion of cholesterol crystals in a limited space during crystallization may contribute to plaque rupture. To evaluate the effect of cholesterol crystal growth on atherosclerotic plaques, we modeled the expansion of cholesterol crystals during the crystallization process in the necrotic core and estimated the stress on the thin cap with different arrangements of cholesterol crystals. We developed a two-dimensional finite element method model of atherosclerotic plaques containing expanding cholesterol crystals and investigated the effect of the magnitude and distribution of crystallization on the peak circumferential stress born by the cap. Using micro-optical coherence tomography (μOCT), we extracted the cross-sectional geometric information of cholesterol crystals in human atherosclerotic aorta tissue ex vivo and applied the information to the model. The results demonstrate that (1) the peak circumference stress is proportionally dependent on the cholesterol crystal growth; (2) cholesterol crystals at the cap shoulder impose the highest peak circumference stress; and (3) spatial distributions of cholesterol crystals have a significant impact on the peak circumference stress: evenly distributed cholesterol crystals exert less peak circumferential stress on the cap than concentrated crystals. PMID:27149381

  17. High-density lipoproteincholesterol, reverse cholesterol transport, and cardiovascular risk: a tale of genetics?

    Directory of Open Access Journals (Sweden)

    Giovanni Cimmino

    2013-10-01

    Full Text Available Cholesterol deposition plays a central role in atherogenesis. The accumulation of lipid material is the result of an imbalance between the influx and efflux of cholesterol within the arterial wall. High levels of plasma low-density lipoprotein-cholesterol are considered the major mechanism responsible for the influx and accumulation of cholesterol in the arterial wall, while high-density lipoprotein (HDL- cholesterol seems responsible for its efflux. The mechanism by which cholesterol is removed from extra-hepatic organs and delivered to the liver for its catabolism and excretion is called reverse cholesterol transport (RCT. Epidemiological evidence has associated high levels of HDL-cholesterol/ApoA-I with protection against atherosclerotic disease, but the ultimate mechanism(s responsible for the beneficial effect is not well established. HDLs are synthesized by the liver and small intestine and released to the circulation as a lipid-poor HDL (nascent HDL, mostly formed by ApoA-I and phospholipids. Through their metabolic maturation, HDLs interact with the ABCA1 receptor in the macrophage surface increasing their lipid content by taking phospholipids and cholesterol from macrophages becoming mature HDL. The cholesterol of the HDLs is transported to the liver, via the scavenger receptor class B, type I, for further metabolization and excretion to the intestines in the form of bile acids and cholesterol, completing the process of RCT. It is clear that an inherited mutation or acquired abnormality in any of the key players in RCT mat affect the atherosclerotic process.

  18. EFFECT OF DIETARY OLIVE OIL/CHOLESTEROL ON SERUM LIPOPROTEINS, LIPID PEROXIDATION, AND ATHEROSCLEROSIS IN RABBITS

    Directory of Open Access Journals (Sweden)

    R MAHDAVI

    2003-03-01

    Full Text Available Introduction: High plasma cholesterol levels, mainly LDL are a widely recognized major risk factor for Coronary Heart Disease (CHD. According to the epidemiologic studies findings, people from the Mediterranean countries, have lower CHD rats than other countries, in these countries usual diet is high in olive oil. The present study compares the effects of cholesterol enriched diet with or without adding olive oil on serum Lipoproteins, lipid per oxidation, and atherosclerosis development. Method: Twenty Dutch male rabbits were Categorized to four groups (one group as Control, and others as Experimental. They received one of standard, cholesterol - rich, olive oil rich and combined (cholesterol + olive oil diet for Twelve weeks. Fasting blood samples from heart were collected at the beginning, and the end of Experimental period. Means of total cholesterol, HDL-Ctriglycerides, MDA and antioxidant caperimental period, significant differences were showed in total cholesterol, HDL-C, triglyceride and MDA between groups. Results: The comparison of cholesterol rich diet with cholesterol + olive oil showed a higher mean of MDA in cholesterol rich group (P < 0.001. Biochemical factors and aortic lesion degree showed no significant difference between standard and olive oil group. Aortic lesions in cholesterol + olive oil showed nonsignificant lower degree than cholesterol group. Discussion: This findings showed preventive effect of olive oil against atherosclerosis which is independent of plasma lipoprotein effect, and suggested that probably olive oil acts on arteries directly.

  19. In vitro determination of the solubility limit of cholesterol in phospholipid bilayers.

    Science.gov (United States)

    Epand, Richard M; Bach, Diana; Wachtel, Ellen

    2016-09-01

    Cholesterol has limited solubility in phospholipid bilayers. The solubility limit is strongly dependent on the nature of the lipid with which the cholesterol is mixed while properties of the crystals formed can be modified by phospholipid-cholesterol interactions. In this review we summarize the various methods that have been developed to prepare hydrated mixtures of cholesterol and phospholipid. We point out some of the factors that determine the form adopted when cholesterol crystallizes in such mixtures, i.e. two- or three-dimensional, monohydrate or anhydrous. These differences can greatly affect the ability to experimentally detect the presence of these crystals in a membrane. Several methods for detecting cholesterol crystals are discussed and compared including DSC, X-ray and GIXRD diffraction methods, NMR and EPR spectroscopy. The importance of the history of the sample in determining the amount and nature of the cholesterol crystals formed is emphasized. PMID:27370110

  20. HDL Cholesterol Efflux Capacity: Cardiovascular Risk Factor and Potential Therapeutic Target.

    Science.gov (United States)

    Bhatt, Anish; Rohatgi, Anand

    2016-01-01

    Low high-density lipoprotein cholesterol (HDL-C) levels are associated with incident cardiovascular events; however, many therapies targeting increases in HDL-C have failed to show consistent clinical benefit. Thus, focus has recently shifted toward measuring high-density lipoprotein (HDL) function. HDL is the key mediator of reverse cholesterol transport, the process of cholesterol extraction from foam cells, and eventual excretion into the biliary system. Cholesterol efflux from peripheral macrophages to HDL particles has been associated with atherosclerosis in both animals and humans. We review the mechanism of cholesterol efflux and the emerging evidence on the association between cholesterol efflux capacity and cardiovascular disease in human studies. We also focus on the completed and ongoing trials of novel therapies targeting different aspects of HDL cholesterol efflux. PMID:26710794

  1. Stanol esters attenuate the aggravating effect of dietary cholesterol on atherosclerosis in homozygous Watanabe rabbits

    DEFF Research Database (Denmark)

    Schrøder, Malene; Husche, Constanze; Pilegaard, Kirsten;

    2009-01-01

    Plant stanols are marketed as natural means to lower blood cholesterol in humans; hence the effect on combined familial hyperlipidemia is not known. The objective was to investigate the effect of stanol esters on blood lipids and aortic atherosclerosis in homozygous WHHL rabbits challenged with...... dietary cholesterol. A total of 36 rabbits, 6 weeks of age, with initial plasma cholesterol of 22.5 mmol/L were assigned to two treatment groups fed a standard rabbit chow with 1 g/kg cholesterol or this diet added 34 g/kg stanol ester, respectively, for 16 weeks. Plasma cholesterol was measured initially...... and at termination, also in lipoproteins. Aortic atherosclerosis was evaluated as cholesterol content and area covered by plaque. Plasma cholesterol was not significantly different between the groups at termination (35.7 mmol/L vs. 35.5 mmol/L). A significant increase in LDL was seen (13.1 mmol/L vs...

  2. Melittin-induced cholesterol reorganization in lipid bilayer membranes.

    Science.gov (United States)

    Qian, Shuo; Heller, William T

    2015-10-01

    The peptide melittin, a 26 amino acid, cationic peptide from honey bee (Apis mellifera) venom, disrupts lipid bilayer membranes in a concentration-dependent manner. Rather than interacting with a specific receptor, the peptide interacts directly with the lipid matrix of the membrane in a manner dependent on the lipid composition. Here, a small-angle neutron scattering study of the interaction of melittin with lipid bilayers made of mixtures of dimyristoylphosphatidylcholine (DMPC) and cholesterol (Chol) is presented. Through the use of deuterium-labeled DMPC, changes in the distribution of the lipid and cholesterol in unilamellar vesicles were observed for peptide concentrations below those that cause pores to form. In addition to disrupting the in-plane organization of Chol, melittin produces vesicles having inner and outer leaflet compositions that depend on the lipid-Chol molar ratio and on the peptide concentration. The changes seen at high cholesterol and low peptide concentration are similar to those produced by alamethicin (Qian, S. et al., J. Phys. Chem. B 2014, 118, 11200-11208), which points to an underlying physical mechanism driving the redistribution of Chol, but melittin displays an additional effect not seen with alamethicin. A model for how the peptide drives the redistribution of Chol is proposed. The results suggest that redistribution of the lipids in a target cell membrane by membrane active peptides takes places as a prelude to the lysis of the cell. PMID:26074009

  3. Cholesterol tethered bioresponsive polycation as a candidate for gene delivery

    International Nuclear Information System (INIS)

    The efficient unpacking of viral protein shell gave the inspiration for the synthesized vectors. In this research, novel cholesterol tethered bioresponsive polyethylenimine (PEI) was specially designed via disulfide-containing cross-linker. The cholesterol lipid had proved to increase the permeability of gene vector through cell membrane. The acid-base titration indicated that the synthesized polycation possessed efficient proton sponge effect, which was suggested to increase endosomal release of pDNA complexes into the cytoplasm. The cholesterol tethered polycation could effectively induce DNA condensation and form spherical particles with diameter about 200 nm at N/P ratio of 10. At glutathione concentration of 3 mM, the polyplexes were unpacked due to the bioresponsive cleavage of the disulfide bonds. The in-vitro experiment indicated that the polyplexes showed efficient transfection efficiency to HEK293T cells. All the results indicated that the bioresponsive polycation could be served as an effective trigger to control the release of DNA at the intracellular environment. The novel bioresponsive polycation might have great potential in non-viral gene delivery research and application.

  4. Cholesterol induces proliferation of chicken primordial germ cells.

    Science.gov (United States)

    Chen, Dongyang; Chen, Meijuan; Lu, Zhenping; Yang, Mengmeng; Xie, Long; Zhang, Wenxin; Xu, Huiyan; Lu, Kehuan; Lu, Yangqing

    2016-08-01

    Primordial germ cells (PGCs) are the precursors of sperm and eggs and may serve as suitable cells for use in research in developmental biology and transgenic animals. However, the long-term propagation of PGCs in vitro has so far been plagued by the loss of their germ cell characteristics. This is largely because of the scarcity of knowledge concerning cell division and proliferation in these cells and the poor optimization of the culture medium. The sonic hedgehog (SHH) signaling pathway is involved in proliferation of many types of cells, but little is known about its role in chicken PGCs. The results of the current study indicate that the proliferation of chicken PGCs increases significantly when cholesterol, a molecule that facilitates the trafficking of HH ligands, is supplemented in the culture medium. This effect was attenuated when an SHH antagonist, cyclopamine was added, suggesting the involvement of SHH signaling in this process. The characterization of PGCs treated with cholesterol has shown that these cells express germ-cell-related markers and retain their capability to colonize the embryonic gonad after re-introduction to vasculature of stage-15 HH embryos, indicating that proliferation of PGCs induced by cholesterol does not alter the germ cell characteristics of these cells. PMID:27269880

  5. Paradoxical impact of cholesterol on lipid packing and cell stiffness.

    Science.gov (United States)

    Ayee, Manuela A; Levitan, Irena

    2016-01-01

    Cell stiffness or deformability is a fundamental property that is expected to play a major role in multiple cellular functions. It is well known that cell stiffness is dominated by the intracellular cytoskeleton that, together with the plasma membrane, forms a membrane-cytoskeleton envelope. However, our understanding of how lipid composition of plasma membrane regulates physical properties of the underlying cytoskeleton is only starting to emerge. In this review, we first briefly describe the impact of cholesterol on the physical properties of lipid bilayers in model membranes and in living cells, with the dominant effect of increasing the order of membrane lipids and decreasing membrane fluidity. Then, we discuss accumulating evidence that removal of cholesterol, paradoxically, decreases the mobility of membrane proteins and increases cellular stiffness, with both effects being dependent on the integrity of the cytoskeleton. Finally, we discuss emerging evidence that oxidized modifications of low-density lipoproteins (oxLDL) have the same effects on endothelial biomechanical properties as cholesterol depletion, an effect that is mediated by the incorporation of oxysterols into the membrane. PMID:27100504

  6. Cholesterol tethered bioresponsive polycation as a candidate for gene delivery

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Ying [Second Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310009 (China); Wang Youxiang, E-mail: yx_wang@zju.edu.cn [Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Key Laboratory of Macromolecular Synthesis and Functionalization, Ministry of Education, Zhejiang University, Hangzhou 310027 (China); Hu Qiaoling; Shen Jiacong [Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Key Laboratory of Macromolecular Synthesis and Functionalization, Ministry of Education, Zhejiang University, Hangzhou 310027 (China)

    2009-04-30

    The efficient unpacking of viral protein shell gave the inspiration for the synthesized vectors. In this research, novel cholesterol tethered bioresponsive polyethylenimine (PEI) was specially designed via disulfide-containing cross-linker. The cholesterol lipid had proved to increase the permeability of gene vector through cell membrane. The acid-base titration indicated that the synthesized polycation possessed efficient proton sponge effect, which was suggested to increase endosomal release of pDNA complexes into the cytoplasm. The cholesterol tethered polycation could effectively induce DNA condensation and form spherical particles with diameter about 200 nm at N/P ratio of 10. At glutathione concentration of 3 mM, the polyplexes were unpacked due to the bioresponsive cleavage of the disulfide bonds. The in-vitro experiment indicated that the polyplexes showed efficient transfection efficiency to HEK293T cells. All the results indicated that the bioresponsive polycation could be served as an effective trigger to control the release of DNA at the intracellular environment. The novel bioresponsive polycation might have great potential in non-viral gene delivery research and application.

  7. LXR regulate cholesterol homeostasis in the proximal mouse epididymis.

    Directory of Open Access Journals (Sweden)

    Jean-Marc A Lobaccaro

    2010-01-01

    Full Text Available Oxysterol nuclear receptors liver x receptors (LXRalpha and LXRbeta regulate lipid homeostasis when cells have to face high amounts of cholesterol and/or fatty acids. Male mice invalidated for both lxr (LXR-/- are infertile by 5 months of age, and become sterile by the age of 9 months. The epididymis was previously shown to be affected by the gene invalidation, a phenotype specifically located in the two proximal segments of this organ. We demonstrate here that cholesteryl esters are accumulated in a specific cell type of the epididymal epithelium, the apical cells, in these two first segments, in LXR-/- male mice. These accumulations are correlated to a decrease in the amount of a specific membrane cholesterol transporter, ATP-binding cassette A1 (ABCA1 in the caput epididymidis of LXR-/- mice. This decrease is due to a transcriptional down-regulation, and we further demonstrate that ABCA1, in the two first segments of the caput epididymidis, is located in the apical cells, and that its accumulation is lost in these cells for LXR-/- male mice as soon as 4 months of age. These data bring new elements in the cholesterol trafficking pathways in the epididymis, and will help a better understanding of the molecular mechanisms occurring in this organ in relation to the sperm cells maturation process.

  8. [Inborn error of cholesterol biosynthesis: Smith-Lemli-Opitz syndrome].

    Science.gov (United States)

    Koczok, Katalin; V Oláh, Anna; P Szabó, Gabriella; Oláh, Éva; Török, Olga; Balogh, István

    2015-10-18

    Smith-Lemli-Opitz syndrome is an autosomal recessive mental retardation and multiple malformation syndrome caused by deficiency of the 7-dehydrocholesterol reductase, the enzyme catalyzing the last step in cholesterol biosynthesis. The authors summarize the pathophysiology, epidemiology, clinical picture, diagnostics and therapy of the disease based on a review of the international literature. Since 2004, fourteen patients have been diagnosed with Smith-Lemli-Opitz syndrome in Hungary, which suggests an underdiagnosis of the disease based upon estimated incidence data. Due to deficiency of the 7-dehydrocholesterol reductase, serum cholesterol concentration is low and 7-dehydrocholesterol concentration is elevated in blood and tissues; the latter being highly specific for the syndrome. Detection of disease-causing mutations makes the prenatal diagnosis possible. The clinical spectrum is wide, the most common symptom is syndactyly of the second and third toes. Standard therapy is cholesterol supplementation. Recent publications suggest that oxidative compounds of 7-dehydrocholesterol may play a role in the pathophysiology of the disease as well. PMID:26551309

  9. FLIM studies of 22- and 25-NBD-cholesterol in living HEK293 cells: plasma membrane change induced by cholesterol depletion.

    Science.gov (United States)

    Ostašov, Pavel; Sýkora, Jan; Brejchová, Jana; Olżyńska, Agnieszka; Hof, Martin; Svoboda, Petr

    2013-01-01

    HEK293 cells stably expressing δ-opioid receptor were labeled first with fluorescent analog of cholesterol, 22-NBD-cholesterol, exposed to cholesterol-depleting agent β-cyclodextrin (β-CDX) and analyzed by fluorescence lifetime imaging microscopy (FLIM). In accordance with chemical analysis of cholesterol level, the total cellular signal of this probe was decreased to half. Distribution of lifetime (τtot) values of 22-NBD-cholesterol, however, when screened over the whole cell area indicated no significant difference between control (τtot=4.9±0.1 ns) and β-CDX-treated (τtot=4.8±0.1 ns) cells. On the contrary, comparison of control (τtot=5.1±0.1 ns) and β-CDX-treated (τtot=4.4±0.1 ns) cells by analysis of 25-NBD-cholesterol fluorescence implied highly significant decrease of lifetime values of this probe. The observation that 22-NBD-cholesterol appears to be indifferent to the changes in the membrane packing in living cells is in agreement with previous studies in model membranes. However, our data indicate that the alternation of plasma membrane structure induced by decrease of cholesterol level by β-CDX makes the membrane environment of NBD moiety of 25-NBD-cholesterol probe a significantly more hydrated. This finding not only encourages using 25-NBD-cholesterol in living cells, but also demonstrates that previously drawn discouraging conclusions on the use of 25-NBD-cholesterol in model membranes are not valid for living cells. PMID:23466534

  10. [Comparison of calculated LDL cholesterol (LDL-C) versus measured LDL cholesterol (LDL-M) and potential impact in terms of therapeutic management].

    Science.gov (United States)

    Reignier, Arnaud; Sacchetto, Emilie; Hardouin, Jean-Benoît; Orsonneau, Jean-Luc; Le Carrer, Didier; Delaroche, Odile; Bigot-Corbel, Edith

    2014-01-01

    LDL-cholesterol value is one of the criteria used by the Haute autorité de santé (HAS) in the management of patients in primary and secondary prevention with the aim to reduce cardiovascular mortality. In this respect, the recommendations have been established based on target to achieve LDL-cholesterol. Currently in France, the determination of LDL-cholesterol is mainly carried out by the Friedewald formula whose limits are well known. However, reliable methods for the determination of LDL-cholesterol exist. We compared the results of calculated and measured LDL-cholesterol obtained from 444 patients presenting normal triglyceridemia values in terms of ranking relative to the thresholds of the HAS. The correlation between the two methods is quite good, but a significant difference (p <0.0001) was observed between the calculated and measured values of LDL-cholesterol. On the other hand in 17% of cases the classification of subjects will be different, with a majority so overestimation of calculated LDL-cholesterol with respect to measured LDL-cholesterol. This overestimation is not proportional, in fact most values measured LDL-cholesterol, the higher the calculate-measured difference is important. The rating difference is particularly important when subjects have between 1 and 3 factors of cardiovascular risk where the target LDL-cholesterol to achieve is between 1.3 and 1.9 g/L. The management of patients with lipid lowering may potentially be dependent on the method used for the determination of LDL-cholesterol. PMID:25336132

  11. Cholesterol in the rod outer segment: A complex role in a "simple" system.

    Science.gov (United States)

    Albert, Arlene; Alexander, Desiree; Boesze-Battaglia, Kathleen

    2016-09-01

    The rod outer segment (ROS) of retinal photoreceptor cells consists of disk membranes surrounded by the plasma membrane. It is a relatively uncomplicated system in which to investigate cholesterol distribution and its functional consequences in biologically relevant membranes. The light sensitive protein, rhodopsin is the major protein in both membranes, but the lipid compositions are significantly different in the disk and plasma membranes. Cholesterol is high in the ROS plasma membrane. Disk membranes are synthesized at the base of the ROS and are also high in cholesterol. However, cholesterol is rapidly depleted as the disks are apically displaced. During this apical displacement the disk phospholipid fatty acyl chains become progressively more unsaturated, which creates an environment unfavorable to cholesterol. Membrane cholesterol has functional consequences. The high cholesterol found in the plasma membrane and in newly synthesized disks inhibits the activation of rhodopsin. As disks are apically displaced and cholesterol is depleted rhodopsin becomes more responsive to light. This effect of cholesterol on rhodopsin activation has been shown in both native and reconstituted membranes. The modulation of activity can be at least partially explained by the effect of cholesterol on bulk lipid properties. Cholesterol decreases the partial free volume of the hydrocarbon region of the bilayer and thereby inhibits rhodopsin conformational changes required for activation. However, cholesterol binds to rhodopsin and may directly affect the protein also. Furthermore, cholesterol stabilizes rhodopsin to thermal denaturation. The membrane must provide an environment that allows rhodopsin conformational changes required for activation while also stabilizing the protein to thermal denaturation. Cholesterol thus plays a complex role in modulating the activity and stability of rhodopsin, which have implications for other G-protein coupled receptors. PMID:27216754

  12. Perspective on plasma membrane cholesterol efflux and spermatozoal function

    Directory of Open Access Journals (Sweden)

    Dhastagir Sultan Sheriff

    2010-01-01

    techniques for enhancing fertility, identifying and treating certain forms of male infertility, and preventing conception. One remarkable insight is the importance of membrane cholesterol efflux in initiating transmembrane signaling events that confer fertilization competence. The identity of the physiologically relevant cholesterol acceptors and modulators of cholesterol efflux is therefore of great interest. Still, it is clear that cholesterol efflux represents only a part of this story. The involvement of phospholipid translocation in mediating dynamic changes in the membrane, rendering it conducive to transmembrane signaling, and the modulation of membrane components of signal transduction cascades by cholesterol or phospholipids will yield important insights into the links between environmental sensing and transmembrane signaling in the sperm. Understanding the membrane molecular events will ultimately provide new and exciting areas of investigation for the future.

  13. Dynamical modeling of the cholesterol regulatory pathway with Boolean networks

    Directory of Open Access Journals (Sweden)

    Corcos Laurent

    2008-11-01

    Full Text Available Abstract Background Qualitative dynamics of small gene regulatory networks have been studied in quite some details both with synchronous and asynchronous analysis. However, both methods have their drawbacks: synchronous analysis leads to spurious attractors and asynchronous analysis lacks computational efficiency, which is a problem to simulate large networks. We addressed this question through the analysis of a major biosynthesis pathway. Indeed the cholesterol synthesis pathway plays a pivotal role in dislypidemia and, ultimately, in cancer through intermediates such as mevalonate, farnesyl pyrophosphate and geranyl geranyl pyrophosphate, but no dynamic model of this pathway has been proposed until now. Results We set up a computational framework to dynamically analyze large biological networks. This framework associates a classical and computationally efficient synchronous Boolean analysis with a newly introduced method based on Markov chains, which identifies spurious cycles among the results of the synchronous simulation. Based on this method, we present here the results of the analysis of the cholesterol biosynthesis pathway and its physiological regulation by the Sterol Response Element Binding Proteins (SREBPs, as well as the modeling of the action of statins, inhibitor drugs, on this pathway. The in silico experiments show the blockade of the cholesterol endogenous synthesis by statins and its regulation by SREPBs, in full agreement with the known biochemical features of the pathway. Conclusion We believe that the method described here to identify spurious cycles opens new routes to compute large and biologically relevant models, thanks to the computational efficiency of synchronous simulation. Furthermore, to the best of our knowledge, we present here the first dynamic systems biology model of the human cholesterol pathway and several of its key regulatory control elements, hoping it would provide a good basis to perform in silico

  14. An amperometric bienzymatic cholesterol biosensor based on functionalized graphene modified electrode and its electrocatalytic activity towards total cholesterol determination.

    Science.gov (United States)

    Manjunatha, Revanasiddappa; Shivappa Suresh, Gurukar; Melo, Jose Savio; D'Souza, Stanislaus F; Venkatesha, Thimmappa Venkatarangaiah

    2012-09-15

    Cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) have been covalently immobilized onto functionalized graphene (FG) modified graphite electrode. Enzymes modified electrodes were characterized using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). FG accelerates the electron transfer from electrode surface to the immobilized ChOx, achieving the direct electrochemistry of ChOx. A well defined redox peak was observed, corresponding to the direct electron transfer of the FAD/FADH(2) of ChOx. The electron transfer coefficient (α) and electron transfer rate constant (K(s)) were calculated and their values are found to be 0.31 and 0.78 s(-1), respectively. For the free cholesterol determination, ChOx-FG/Gr electrode exhibits a sensitive response from 50 to 350 μM (R=-0.9972) with a detection limit of 5 μM. For total cholesterol determination, co-immobilization of ChEt and ChOx on modified electrode, i.e. (ChEt/ChOx)-FG/Gr electrode showed linear range from 50 to 300 μM (R=-0.9982) with a detection limit of 15 μM. Some common interferents like glucose, ascorbic acid and uric acid did not cause any interference, due to the use of a low operating potential. The FG/Gr electrode exhibits good electrocatalytic activity towards hydrogen peroxide (H(2)O(2)). A wide linear response to H(2)O(2) ranging from 0.5 to 7 mM (R=-0.9967) with a sensitivity of 443.25 μA mM(-1) cm(-2) has been obtained. PMID:22967556

  15. Cholesterol 7α-hydroxylase-deficient mice are protected from high-fat/high-cholesterol diet-induced metabolic disorders.

    Science.gov (United States)

    Ferrell, Jessica M; Boehme, Shannon; Li, Feng; Chiang, John Y L

    2016-07-01

    Cholesterol 7α-hydroxylase (CYP7A1) is the first and rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver. In addition to absorption and digestion of nutrients, bile acids play a critical role in the regulation of lipid, glucose, and energy homeostasis. We have backcrossed Cyp7a1(-/-) mice in a mixed B6/129Sv genetic background to C57BL/6J mice to generate Cyp7a1(-/-) mice in a near-pure C57BL/6J background. These mice survive well and have normal growth and a bile acid pool size ∼60% of WT mice. The expression of the genes in the alternative bile acid synthesis pathway are upregulated, resulting in a more hydrophilic bile acid composition with reduced cholic acid (CA). Surprisingly, Cyp7a1(-/-) mice have improved glucose sensitivity with reduced liver triglycerides and fecal bile acid excretion, but increased fecal fatty acid excretion and respiratory exchange ratio (RER) when fed a high-fat/high-cholesterol diet. Supplementing chow and Western diets with CA restored bile acid composition, reversed the glucose tolerant phenotype, and reduced the RER. Our current study points to a critical role of bile acid composition, rather than bile acid pool size, in regulation of glucose, lipid, and energy metabolism to improve glucose and insulin tolerance, maintain metabolic homeostasis, and prevent high-fat diet-induced metabolic disorders. PMID:27146480

  16. High pre-beta1 HDL concentrations and low lecithin: cholesterol acyltransferase activities are strong positive risk markers for ischemic heart disease and independent of HDL-cholesterol

    DEFF Research Database (Denmark)

    Sethi, Amar A; Sampson, Maureen; Warnick, Russell;

    2010-01-01

    We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors.......We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors....

  17. Cholesterol esterification by mouse liver homogenate. Contribution to the study of ACYL-CoA: Cholesterol ACYL transferase in mammalian liver

    International Nuclear Information System (INIS)

    A cholesterol- esterifying enzyme from mouse liver has been partially characterized. The enzyme which showed optimum activity at pH 7,1 and required ATP and CoA, was identified as an acyl CoA: cholesterol acyl transferase (E.C.2.3.1.26). As a fuction of time the percentage of esterified cholesterol increased linearly during the first hour of incubation and continued to increase but not linearly with 4 hours, after which time no further net esterefication was observed. The relative concentration of esterified cholesterol remained constant between the fourth and twelveth hours of incubation but afterwards decreased when the incubation continued until 24 hours. The cholesterol- esterifying activity was 24,0+- 2,9 nmoles cholesterol esterified per gram tissue wet weight per minute. The mean percentages of free cholesterol esterified in and 24 hours respectively were 14,8+- 1,6 e 21,9+- 4,5. The subfractionation of labelled cholesteryl esters after one hour incubation of liver homogenate with 4-C14-Cholesterol showed the order of preference for the formation of the different ester classes to be monounsatured > diunsatured ≥ saturated >> polyunsaturated. The properties of the enzyme frommouse liver do not markedly differ from those of the previously recorded ACAT activity of rat liver. (Author)

  18. Protein complexes and cholesterol in the control of late endosomal dynamicsCholesterol and multi-protein complexes in the control of late endosomal dynamics

    NARCIS (Netherlands)

    Kant, Rik Henricus Nicolaas van der

    2013-01-01

    Late endosomal transport is disrupted in several diseases such as Niemann-Pick type C, ARC syndrome and Alzheimer’s disease. This thesis describes the regulation of late endosomal dynamics by cholesterol and multi-protein complexes. We find that cholesterol acts as a cellular tomtom that steers the

  19. Lathosterol to cholesterol ratio in serum predicts cholesterol lowering response to plant sterol consumption in a dual center, randomized, single-blind placebo controlled trial

    Science.gov (United States)

    Benefits of plant sterols (PS) for cholesterol lowering are compromised by large variability in efficacy across individuals. High fractional cholesterol synthesis measured by deuterium incorporation has been associated with non-response to PS consumption; however, prospective studies showing this as...

  20. Cholesterol loaded cyclodextrin increases freezability of buffalo bull (Bubalus bubalis spermatozoa by increasing cholesterol to phospholipid ratio

    Directory of Open Access Journals (Sweden)

    J. S. Rajoriya

    2014-09-01

    Full Text Available Aim: The study was conducted to investigate the effect of cholesterol loaded cyclodextrin (CLC on freezability of buffalo spermatozoa. Materials and Methods: Murrah buffalo bull semen samples with progressive motility of 70% and greater were used. After the evaluation of motility and livability, four equal fractions of semen samples were made. Group I was kept as control and diluted with Tris, whereas Group II, III and IV were treated with CLC solution at the rate of 2.0, 3.0 and 4.0 mg/ml respectively to obtain 120 × 106 sperm/ml as final spermatozoa concentration. The aliquots of all the groups were incubated for action of CLC, followed by dilution and freezing. Evaluation at pre-freeze and post-thaw stage of progressive motility, viability and level of cholesterol and phospholipid was done. Results: The mean cholesterol content (μg/100 × 106 spermatozoa of Group I, II, III and IV at pre-freeze stage was 21.55±0.63, 49.56±1.38, 55.67±0.45 and 47.79±1.01 and at post-thaw stage were 13.18±0.45, 34.27±0.71, 36.21±0.48 and 33.68±0.56, respectively. At pre-freeze stage, cholesterol content was significantly (p<0.01 higher in Group III in comparison to other groups. The mean cholesterol and phospholipids content of fresh sperm was 24.14±0.58 and 51.13±0.66 μg/100 × 106 sperm cells, respectively, and C/P ratio of spermatozoa at fresh stage was 0.47±0.067. Conclusion: CLC treatment maintains the C/P ratio and plays an important role in maintaining membrane architecture of spermatozoa. Hence, addition of CLC may be helpful in increasing freezability of buffalo spermatozoa by increasing the C/P ratio of spermatozoa.

  1. Revisiting Human Cholesterol Synthesis and Absorption: The Reciprocity Paradigm and its Key Regulators.

    Science.gov (United States)

    Alphonse, Peter A S; Jones, Peter J H

    2016-05-01

    Hypercholesterolemia is a major risk factor for cardiovascular disease. Cholesterol homeostasis in the body is governed by the interplay between absorption, synthesis, and excretion or conversion of cholesterol into bile acids. A reciprocal relationship between cholesterol synthesis and absorption is known to regulate circulating cholesterol in response to dietary or therapeutic interventions. However, the degree to which these factors affect synthesis and absorption and the extent to which one vector shifts in response to the other are not thoroughly understood. Also, huge inter-individual variability exists in the manner in which the two systems act in response to any cholesterol-lowering treatment. Various factors are known to account for this variability and in light of recent experimental advances new players such as gene-gene interactions, gene-environmental effects, and gut microbiome hold immense potential in offering an explanation to the complex traits of inter-individual variability in human cholesterol metabolism. In this context, the objective of the present review is to provide an overview on cholesterol metabolism and discuss the role of potential factors such as genetics, epigenetics, epistasis, and gut microbiome, as well as other regulators in modulating cholesterol metabolism, especially emphasizing the reciprocal relationship between cholesterol synthesis and absorption. Furthermore, an evaluation of the implications of this push-pull mechanism on cholesterol-lowering strategies is presented. PMID:26620375

  2. Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport.

    Science.gov (United States)

    Fernández-Suárez, María E; Escolà-Gil, Joan C; Pastor, Oscar; Dávalos, Alberto; Blanco-Vaca, Francisco; Lasunción, Miguel A; Martínez-Botas, Javier; Gómez-Coronado, Diego

    2016-01-01

    Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17β-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [(3)H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [(3)H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages. PMID:27601313

  3. Rice bran proteins and their hydrolysates modulate cholesterol metabolism in mice on hypercholesterolemic diets.

    Science.gov (United States)

    Zhang, Huijuan; Wang, Jing; Liu, Yingli; Gong, Lingxiao; Sun, Baoguo

    2016-06-15

    The hypolipidemic properties of defatted rice bran protein (DRBP), fresh rice bran protein (FRBP), DRBP hydrolysates (DRBPH), and FRBP hydrolysates (FRBPH) were determined in mice on high fat diets for four weeks. Very low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C) contents, and the hepatic total cholesterol content were reduced while fecal total cholesterol and total bile acid (TBA) contents were increased in the FRBPH diet group. The expression levels of hepatic genes for cholesterol biosynthesis HMG-CoAR and SREBP-2 were lowest in the FRBPH diet group. The mRNA level of HMG-CoAR was significantly positively correlated with the hepatic TG content (r = 0.82, P < 0.05). The mRNA levels of genes related to bile acid biosynthesis and cholesterol efflux, CYP7A1, ABCA1, and PPARγ were up-regulated in all test groups. The results suggest that FRBPH regulates cholesterol metabolism in mice fed the high fat and cholesterol diet by increasing fecal steroid excretion and expression levels of genes related to bile acid synthesis and cholesterol efflux, and the down-regulation of the expression levels of genes related to cholesterol biosynthesis. PMID:27216972

  4. Cholesterol as a causative factor in Alzheimer's disease: a debatable hypothesis.

    Science.gov (United States)

    Wood, W Gibson; Li, Ling; Müller, Walter E; Eckert, Gunter P

    2014-05-01

    High serum/plasma cholesterol levels have been suggested as a risk factor for Alzheimer's disease (AD). Some reports, mostly retrospective epidemiological studies, have observed a decreased prevalence of AD in patients taking the cholesterol lowering drugs, statins. The strongest evidence causally linking cholesterol to AD is provided by experimental studies showing that adding/reducing cholesterol alters amyloid precursor protein (APP) and amyloid beta-protein (Ab) levels. However, there are problems with the cholesterol-AD hypothesis. Cholesterol levels in serum/plasma and brain of AD patients do not support cholesterol as a causative factor in AD.Prospective studies on statins and AD have largely failed to show efficacy. Even the experimental data are open to interpretation given that it is well-established that modification of cholesterol levels has effects on multiple proteins, not only amyloid precursor protein and Ab. The purpose of this review, therefore, was to examine the above-mentioned issues, discuss the pros and cons of the cholesterol-AD hypothesis, involvement of other lipids in the mevalonate pathway, and consider that AD may impact cholesterol homeostasis. PMID:24329875

  5. Mobilization of late-endosomal cholesterol is inhibited by Rab guanine nucleotide dissociation inhibitor.

    Science.gov (United States)

    Hölttä-Vuori, M; Määttä, J; Ullrich, O; Kuismanen, E; Ikonen, E

    2000-01-27

    Cholesterol entering cells in low-density lipoproteins (LDL) via receptor-mediated endocytosis is transported to organelles of the late endocytic pathway for degradation of the lipoprotein particles. The fate of the free cholesterol released remains poorly understood, however. Recent observations suggest that late-endosomal cholesterol sequestration is regulated by the dynamics of lysobisphosphatidic acid (LBPA)-rich membranes [1]. Genetic studies have pinpointed a protein, Niemann-Pick C-1 (NPC-1), that is required for the mobilization of late-endosomal/lysosomal cholesterol by an unknown mechanism [2]. Here, we report the removal of accumulated cholesterol by overexpression of the NPC-1 protein in NPC-1-deficient fibroblasts from patients with Niemann-Pick disease, and in normal fibroblasts upon release of a progesterone-induced block of cholesterol transport. We show that late-endosomal/lysosomal cholesterol mobilization is specifically inhibited by microinjection of Rab GDP-dissociation inhibitor (Rab-GDI). Moreover, clearance of the cholesterol deposits by NPC-1 in patients' fibroblasts is accompanied by the redistribution of LBPA and of a lysosomal hydrolase that utilizes the mannose-6-phosphate receptor. Our results reveal, for the first time, the involvement of a specific molecular component of the membrane-trafficking machinery in cholesterol transport and the coupling of late-endosomal cholesterol egress to the trafficking of other lipid and protein cargo. PMID:10662671

  6. Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model.

    Science.gov (United States)

    Huang, Haiqiu; Xie, Zhuohong; Yokoyama, Wallace; Yu, Liangli; Wang, Thomas T Y

    2016-01-01

    Hypercholesterolaemia is a risk factor for CVD, which is a leading cause of death in industrialised societies. The biosynthetic pathways for cholesterol metabolism are well understood; however, the regulation of circulating cholesterol by diet is still not fully elucidated. The present study aimed to gain more comprehensive understanding of the relationship between circulating cholesterol levels and molecular effects in target tissues using the hamster model. Male golden Syrian hamsters were fed with chow or diets containing 36 % energy from fat with or without 1 % cholesteyramine (CA) as a modulator of circulating cholesterol levels for 35 d. It was revealed that the expression of lanosterol 14α-demethylase (CYP51) instead of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase mRNA expression was responsive to circulating cholesterol in hamsters fed hypercholesterolaemic diets. The high-fat diet increased circulating cholesterol and down-regulated CYP51, but not HMG-CoA reductase. The CA diet decreased cholesterol and increased CYP51 expression, but HMG-CoA reductase expression was not affected. The high-fat diet and CA diet altered the expression level of cholesterol, bile acids and lipid metabolism-associated genes (LDL receptor, cholesterol 7α-hydroxylase (CYP7A1), liver X receptor (LXR) α, and ATP-binding cassette subfamily G member 5/8 (ABCG5/8)) in the liver, which were significantly correlated with circulating cholesterol levels. Correlation analysis also showed that circulating cholesterol levels were regulated by LXR/retinoid X receptor and PPAR pathways in the liver. Using the hamster model, the present study provided additional molecular insights into the influence of circulating cholesterol on hepatic cholesterol metabolism pathways during hypercholesterolaemia. PMID:27110359

  7. Intestine-specific MTP and global ACAT2 deficiency lowers acute cholesterol absorption with chylomicrons and HDLs

    OpenAIRE

    Iqbal, Jahangir; Boutjdir, Mohamed; Rudel, Lawrence L.; Hussain, M. Mahmood

    2014-01-01

    Intestinal cholesterol absorption involves the chylomicron and HDL pathways and is dependent on microsomal triglyceride transfer protein (MTP) and ABCA1, respectively. Chylomicrons transport free and esterified cholesterol, whereas HDLs transport free cholesterol. ACAT2 esterifies cholesterol for secretion with chylomicrons. We hypothesized that free cholesterol accumulated during ACAT2 deficiency may be secreted with HDLs when chylomicron assembly is blocked. To test this, we studied cholest...

  8. Properties of mixtures of cholesterol with phosphatidylcholine or with phosphatidylserine studied by (13)C magic angle spinning nuclear magnetic resonance.

    OpenAIRE

    Epand, Richard M.; Bain, Alex D; Sayer, Brian G; Bach, Diana; Wachtel, Ellen

    2002-01-01

    The behavior of cholesterol is different in mixtures with phosphatidylcholine as compared with phosphatidylserine. In (13)C cross polarization/magic angle spinning nuclear magnetic resonance spectra, resonance peaks of the vinylic carbons of cholesterol are a doublet in samples containing 0.3 or 0.5 mol fraction cholesterol with 1-palmitoyl-2-oleoyl phosphatidylserine (POPS) or in cholesterol monohydrate crystals, but a singlet with mixtures of cholesterol and 1-palmitoyl-2-oleoyl phosphatidy...

  9. The Utilization of Seaweed as a Source of Dietary Fiber to Decrease the Serum Cholesterol in Rats

    OpenAIRE

    MADE ASTAWAN; TUTIK WRESDIYATI; ANZS BUDY HARTANTA

    2005-01-01

    The cholesterol lowering effect of seaweed (Eucheuma cottonii) powder as a source of dietary fiber was evaluated in hypercholesterolemic rats. Four groups of five male Sprague Dawley hypercholesterolemic rats were fed a 0% cholesterol-0% seaweed powder (negative control); 1% cholesterol-5% seaweed powder; 1% cholesterol-10% seaweed powder; and 1% cholesterol-0% seaweed powder (positive control) for 35 days. Seaweed powder contained feed did not affect the growth of rats but significantly lowe...

  10. Microsomal Triglyceride Transfer Protein Enhances Cellular Cholesteryl Esterification by Relieving Product Inhibition*

    OpenAIRE

    Iqbal, Jahangir; Rudel, Lawrence L.; Hussain, M. Mahmood

    2008-01-01

    Cholesteryl ester synthesis by the acyl-CoA:cholesterol acyltransferase enzymes ACAT1 and ACAT2 is, in part, a cellular homeostatic mechanism to avoid toxicity associated with high free cholesterol levels. In hepatocytes and enterocytes, cholesteryl esters are secreted as part of apoB lipoproteins, the assembly of which is critically dependent on microsomal triglyceride transfer protein (MTP). Conditional genetic ablation of MTP reduces cholesteryl esters and enhances ...

  11. Sequestration of free cholesterol in cell membranes by prions correlates with cytoplasmic phospholipase A2 activation

    Directory of Open Access Journals (Sweden)

    Williams Alun

    2008-02-01

    Full Text Available Abstract Background The transmissible spongiform encephalopathies (TSEs, otherwise known as the prion diseases, occur following the conversion of the normal cellular prion protein (PrPC to an alternatively folded isoform (PrPSc. The accumulation of PrPSc within the brain leads to neurodegeneration through an unidentified mechanism. Since many neurodegenerative disorders including prion, Parkinson's and Alzheimer's diseases may be modified by cholesterol synthesis inhibitors, the effects of prion infection on the cholesterol balance within neuronal cells were examined. Results We report the novel observation that prion infection altered the membrane composition and significantly increased total cholesterol levels in two neuronal cell lines (ScGT1 and ScN2a cells. There was a significant correlation between the concentration of free cholesterol in ScGT1 cells and the amounts of PrPSc. This increase was entirely a result of increased amounts of free cholesterol, as prion infection reduced the amounts of cholesterol esters in cells. These effects were reproduced in primary cortical neurons by the addition of partially purified PrPSc, but not by PrPC. Crucially, the effects of prion infection were not a result of increased cholesterol synthesis. Stimulating cholesterol synthesis via the addition of mevalonate, or adding exogenous cholesterol, had the opposite effect to prion infection on the cholesterol balance. It did not affect the amounts of free cholesterol within neurons; rather, it significantly increased the amounts of cholesterol esters. Immunoprecipitation studies have shown that cytoplasmic phospholipase A2 (cPLA2 co-precipitated with PrPSc in ScGT1 cells. Furthermore, prion infection greatly increased both the phosphorylation of cPLA2 and prostaglandin E2 production. Conclusion Prion infection, or the addition of PrPSc, increased the free cholesterol content of cells, a process that could not be replicated by the stimulation of cholesterol

  12. Cholesterol modulates open probability and desensitization of NMDA receptors

    Czech Academy of Sciences Publication Activity Database

    Kořínek, Miloslav; Vyklický, Vojtěch; Borovská, Jiřina; Lichnerová, Katarina; Kaniaková, Martina; Krausová, Barbora; Krůšek, Jan; Balík, Aleš; Smejkalová, Tereza; Horák, Martin; Vyklický ml., Ladislav

    2015-01-01

    Roč. 593, č. 10 (2015), s. 2279-2293. ISSN 0022-3751 R&D Projects: GA ČR(CZ) GPP303/11/P391; GA ČR(CZ) GAP303/12/1464; GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GA14-02219S; GA ČR(CZ) GP14-09220P; GA TA ČR(CZ) TE01020028; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : NMDA receptor * glutamate-gated * cholesterol Subject RIV: ED - Physiology Impact factor: 5.037, year: 2014

  13. Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

    Directory of Open Access Journals (Sweden)

    Mohamed Ramadan El Sayed Aly

    2015-10-01

    Full Text Available 3β-Azidocholest-5-ene (3 and (3β-3-(prop-2-yn-1-yloxycholest-5-ene (10 were prepared as substrates to synthesize a variety of three-motif pharmacophoric conjugates through CuAAC. Basically, these conjugates included cholesterol and 1,2,3-triazole moieties, while the third, the pharmacophore, was either a chalcone, a lipophilic residue or a carbohydrate tag. These compounds were successfully prepared in good yields and characterized by NMR, MS and IR spectroscopic techniques. Chalcone conjugate 6c showed the best antimicrobial activity, while the lactoside conjugate 27 showed the best cytotoxic effect in vitro.

  14. Intercalation of small hydrophobic molecules in lipid bilayers containing cholesterol

    Energy Technology Data Exchange (ETDEWEB)

    Worcester, D.L.; Hamacher, K.; Kaiser, H.; Kulasekere, R.; Torbet, J. [Univ. of Missouri, Columbia, MO (United States)

    1994-12-31

    Partitioning of small hydrophobic molecules into lipid bilayers containing cholesterol has been studied using the 2XC diffractometer at the University of Missouri Research Reactor. Locations of the compounds were determined by Fourier difference methods with data from both deuterated and undeuterated compounds introduced into the bilayers from the vapor phase. Data fitting procedures were developed for determining how well the compounds were localized. The compounds were found to be localized in a narrow region at the center of the hydrophobic layer, between the two halves of the bilayer. The structures are therefore intercalated structures with the long axis of the molecules in the plane of the bilayer.

  15. Cholesterol emboli syndrome - a rare complication of cardiac catheterization

    International Nuclear Information System (INIS)

    We are reporting the case of a 57 years old male, hypertensive, diabetic, dyslipidaemic who presented with exertional angina. He had a coronary artery bypass surgery, one year ago. He underwent left heart catheterization with graft study which showed critical native triple vessel disease with patent arterial graft to left anterior descending and occluded venous grafts to obtuse marginal and right coronary artery. The procedure was complicated by catheter induced dissection of the ascending aorta. Three days later he developed cholesterol emboli syndrome, that was treated symptomatically. (author)

  16. Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

    OpenAIRE

    Mohamed Ramadan El Sayed Aly; Hosam Ali Saad; Shams Hashim Abdel-Hafez

    2015-01-01

    3β-Azidocholest-5-ene (3) and (3β)-3-(prop-2-yn-1-yloxy)cholest-5-ene (10) were prepared as substrates to synthesize a variety of three-motif pharmacophoric conjugates through CuAAC. Basically, these conjugates included cholesterol and 1,2,3-triazole moieties, while the third, the pharmacophore, was either a chalcone, a lipophilic residue or a carbohydrate tag. These compounds were successfully prepared in good yields and characterized by NMR, MS and IR spectroscopic techniques. Chalcone conj...

  17. Peptides having reduced toxicity that stimulate cholesterol efflux

    Energy Technology Data Exchange (ETDEWEB)

    Bielicki, John K.; Johansson, Jan; Danho, Waleed

    2016-08-16

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  18. Chemical constituents from bark of Cenostigma macrophyllum: cholesterol occurrence

    International Nuclear Information System (INIS)

    Phytochemical investigation of the bark of Cenostigma macrophyllum (Leguminosae-Caesapinioideae) resulted in the isolation and identification of valoneic acid dilactone, ellagic acid, lupeol, alkyl ferulate, four free sterols (cholesterol, campesterol, stigmasterol and sitosterol), a mixture of sitosteryl ester derivatives of fatty acids, sitosterol-3-O-beta-D-glucopyranoside, stigmasterol-3-O-beta-D-glucopyranoside and saturated and unsaturated fatty acids. The structures of the isolated compounds were identified by 1H and 13C NMR spectral analysis and comparison with literature data. The mixtures of 3-beta-hydroxysterols and fatty acids were analysed by GC/MS. (author)

  19. Intercalation of small hydrophobic molecules in lipid bilayers containing cholesterol

    International Nuclear Information System (INIS)

    Partitioning of small hydrophobic molecules into lipid bilayers containing cholesterol has been studied using the 2XC diffractometer at the University of Missouri Research Reactor. Locations of the compounds were determined by Fourier difference methods with data from both deuterated and undeuterated compounds introduced into the bilayers from the vapor phase. Data fitting procedures were developed for determining how well the compounds were localized. The compounds were found to be localized in a narrow region at the center of the hydrophobic layer, between the two halves of the bilayer. The structures are therefore intercalated structures with the long axis of the molecules in the plane of the bilayer

  20. Detection of cholesterol-rich microdomains in the inner leaflet of the plasma membrane

    International Nuclear Information System (INIS)

    The C-terminal domain (D4) of perfringolysin O binds selectively to cholesterol in cholesterol-rich microdomains. To address the issue of whether cholesterol-rich microdomains exist in the inner leaflet of the plasma membrane, we expressed D4 as a fusion protein with EGFP in MEF cells. More than half of the EGFP-D4 expressed in stable cell clones was bound to membranes in raft fractions. Depletion of membrane cholesterol with β-cyclodextrin reduced the amount of EGFP-D4 localized in raft fractions, confirming EGFP-D4 binding to cholesterol-rich microdomains. Subfractionation of the raft fractions showed most of the EGFP-D4 bound to the plasma membrane rather than to intracellular membranes. Taken together, these results strongly suggest the existence of cholesterol-rich microdomains in the inner leaflet of the plasma membrane

  1. Novel mechanisms of intracellular cholesterol transport: oxysterol-binding proteins and membrane contact sites.

    Science.gov (United States)

    Du, Ximing; Brown, Andrew J; Yang, Hongyuan

    2015-08-01

    Cholesterol is an essential membrane constituent, and also plays a key role in cell signalling. Within a cell, how cholesterol is transported and how its heterogeneous distribution is maintained are poorly understood. Recent advances have identified novel pathways and regulators of cholesterol trafficking. Sterol transfer by lipid-binding proteins, such as OSBP (oxysterol-binding protein), coupled with phosphatidylinositol 4-phosphate exchange at membrane contact sites (MCSs) has emerged as a new theme of cholesterol transport between organellar membranes. Moreover, a previously unappreciated role of peroxisomes in cholesterol trafficking has been revealed recently. These discoveries highlight the crucial role of MCSs, or junctions, in facilitating lipid movement, and provide mechanistic insights into how cholesterol is sorted in cells. PMID:25932595

  2. How cholesterol interacts with proteins and lipids during its intracellular transport

    DEFF Research Database (Denmark)

    Wüstner, Daniel; Solanko, Katarzyna

    2015-01-01

    Sterols, as cholesterol in mammalian cells and ergosterol in fungi, are indispensable molecules for proper functioning and nanoscale organization of the plasma membrane. Synthesis, uptake and efflux of cholesterol are regulated by a variety of protein-lipid and protein-protein interactions....... Similarly, membrane lipids and their physico-chemical properties directly affect cholesterol partitioning and thereby contribute to the highly heterogeneous intracellular cholesterol distribution. Movement of cholesterol in cells is mediated by vesicle trafficking along the endocytic and secretory pathways...... as well as by non-vesicular sterol exchange between organelles. In this article, we will review recent progress in elucidating sterol-lipid and sterol-protein interactions contributing to proper sterol transport in living cells. We outline recent biophysical models of cholesterol distribution and...

  3. Effect of dimethylsulfoxide on sphingomyelinase activity and cholesterol metabolism in Niemann-Pick type C fibroblasts

    OpenAIRE

    F.B. Scalco; R. Giugliani; P. Tobo; J. C. COELHO

    1999-01-01

    Niemann-Pick type C (NPC) fibroblasts present a large concentration of cholesterol in their cytoplasm due to a still unidentified deficiency in cholesterol metabolism. The influence of dimethylsulfoxide (DMSO) on the amount of intracellular cholesterol was measured in 8 cultures of normal fibroblasts and in 7 fibroblast cultures from NPC patients. DMSO was added to the fibroblast cultures at three different concentrations (1, 2 and 4%, v/v) and the cultures were incubated for 24 h. Sphingomye...

  4. Cholesterol Assimilation by Lactic Acid Bacteria and Bifidobacteria Isolated from the Human Gut

    OpenAIRE

    Dora I A Pereira; Gibson, Glenn R.

    2002-01-01

    The objective of this study was to evaluate the effect of human gut-derived lactic acid bacteria and bifidobacteria on cholesterol levels in vitro. Continuous cultures inoculated with fecal material from healthy human volunteers with media supplemented with cholesterol and bile acids were used to enrich for potential cholesterol assimilators among the indigenous bacterial populations. Seven potential probiotics were found: Lactobacillus fermentum strains F53 and KC5b, Bifidobacterium infantis...

  5. A paradoxical severe decrease in serum HDL-cholesterol after treatment with a fibrate

    OpenAIRE

    Crook, M; Lynas, J; Wray, R

    2000-01-01

    There have been a handful of reports in the literature of a paradoxical decrease in serum high density lipoprotein (HDL)-cholesterol in patients on fibrate drugs. The reason for this decline in cardioprotective HDL-cholesterol is not known and may have potential deleterious effects on the patient. This report describes a decrease in serum HDL-cholesterol in a patient on both simvastatin and bezafibrate. This patient also developed abnormal renal function, probably interstitial nephritis. In a...

  6. Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones

    Directory of Open Access Journals (Sweden)

    Azhar Salman

    2010-06-01

    Full Text Available Abstract Steroid hormones regulate diverse physiological functions such as reproduction, blood salt balance, maintenance of secondary sexual characteristics, response to stress, neuronal function and various metabolic processes. They are synthesized from cholesterol mainly in the adrenal gland and gonads in response to tissue-specific tropic hormones. These steroidogenic tissues are unique in that they require cholesterol not only for membrane biogenesis, maintenance of membrane fluidity and cell signaling, but also as the starting material for the biosynthesis of steroid hormones. It is not surprising, then, that cells of steroidogenic tissues have evolved with multiple pathways to assure the constant supply of cholesterol needed to maintain optimum steroid synthesis. The cholesterol utilized for steroidogenesis is derived from a combination of sources: 1 de novo synthesis in the endoplasmic reticulum (ER; 2 the mobilization of cholesteryl esters (CEs stored in lipid droplets through cholesteryl ester hydrolase; 3 plasma lipoprotein-derived CEs obtained by either LDL receptor-mediated endocytic and/or SR-BI-mediated selective uptake; and 4 in some cultured cell systems from plasma membrane-associated free cholesterol. Here, we focus on recent insights into the molecules and cellular processes that mediate the uptake of plasma lipoprotein-derived cholesterol, events connected with the intracellular cholesterol processing and the role of crucial proteins that mediate cholesterol transport to mitochondria for its utilization for steroid hormone production. In particular, we discuss the structure and function of SR-BI, the importance of the selective cholesterol transport pathway in providing cholesterol substrate for steroid biosynthesis and the role of two key proteins, StAR and PBR/TSO in facilitating cholesterol delivery to inner mitochondrial membrane sites, where P450scc (CYP11A is localized and where the conversion of cholesterol to

  7. A Novel Cholesterol Oxidase Biosensor Based on Pt-nanoparticle /Carbon Nanotube Modified Electrode

    Institute of Scientific and Technical Information of China (English)

    Qiao Cui SHI; Tu Zhi PENG

    2005-01-01

    A Pt-nanoparticle/carbon nanotube modified graphite electrode immobilized with cholesterol oxidase/sol-gel layer was developed for monitoring cholesterol. Using this electrode,cholesterol concentration (4.0×10-6 to 1.0×10 mol/L) could be determined accurately in the presence of ascorbic or uric acid, and the response time was rapid (< 20 s). This biosensor has high sensitivity and selectivity.

  8. Serum Cholesterol Level Nomograms for Iranian Population; Suggestion for National Cut-Offs

    OpenAIRE

    Mostafa Hosseini; Shervin Taslimi; Mahmoud Yousefifard; Fereshteh Asgari; Koorosh Etemad; Hamid Heidarian Miri; Ali Rafei; Jalil Koohpayehzadeh; Iman Navid; Mohammad Mehdi Gouya

    2013-01-01

    Background: High cholesterol levels are associated with increased risk of coronary heart disease and stroke. Understanding the distribution of serum cholesterol levels in each country is valuable index for use in public health planning. This study aimed to construct nomograms of total cholesterol (TC) levels and establish the cut-points specific to Iranian population. Methods: Data on serum TC levels of 19,630 non-institutionalized individuals aged 25–64 years from third national survey on no...

  9. A defect in cholesterol esterification in Niemann-Pick disease (type C) patients.

    OpenAIRE

    Pentchev, P G; Comly, M E; Kruth, H. S.; Vanier, M T; Wenger, D A; Patel, S.; Brady, R O

    1985-01-01

    The demonstration of a defect of cholesterol esterification in a mutant strain of BALB/c mice with an attendant reduction of sphingomyelinase activity [Pentchev, P. G., Boothe, A. D., Kruth, H.S., Weintroub, H., Stivers, J. & Brady, R. O. (1984) J. Biol. Chem. 259, 5784-5791] prompted us to examine the capacity of cultured human Niemann-Pick fibroblasts to esterify exogenously derived cholesterol. Cholesterol was supplied to cell cultures in the form of native or chemically modified, positive...

  10. Cholesterol Accumulation Sequesters Rab9 and Disrupts Late Endosome Function in NPC1-deficient Cells*

    OpenAIRE

    Ganley, Ian G.; Pfeffer, Suzanne R

    2006-01-01

    Niemann-Pick type C disease is an autosomal recessive disorder that leads to massive accumulation of cholesterol and glycosphingolipids in late endosomes and lysosomes. To understand how cholesterol accumulation influences late endosome function, we investigated the effect of elevated cholesterol on Rab9-dependent export of mannose 6-phosphate receptors from this compartment. Endogenous Rab9 levels were elevated 1.8-fold in Niemann-Pick type C cells relative to wild type cells, and its half-l...

  11. The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis

    OpenAIRE

    Rader, Daniel J.; Alexander, Eric T.; Weibel, Ginny L.; Billheimer, Jeffrey; Rothblat, George H.

    2009-01-01

    Reverse cholesterol transport (RCT) is a term used to describe the efflux of excess cellular cholesterol from peripheral tissues and its return to the liver for excretion in the bile and ultimately the feces. It is believed to be a critical mechanism by which HDL exert a protective effect on the development of atherosclerosis. In this paradigm, cholesterol is effluxed from arterial macrophages to extracellular HDL-based acceptors through the action of transporters such as ABCA1 and ABCG1. Aft...

  12. AIBP: A Novel Molecule at the Interface of Cholesterol Transport, Angiogenesis, and Atherosclerosis

    OpenAIRE

    Zhu, Laurence; Fang, Longhou

    2015-01-01

    Cardiovascular disease, which is often driven by hypercholesterolemia and subsequent coronary atherosclerosis, is the number-one cause of morbidity and mortality in the United States. Based on long-term epidemiological studies, high-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with risk for coronary artery disease (CAD). HDL-mediated reverse cholesterol transport (RCT) is responsible for cholesterol removal from the peripheral tissues and return to the liver for fin...

  13. Liver X Receptors as Therapeutic Targets for Managing Cholesterol: Implications for Atherosclerosis and Other Inflammatory Conditions

    OpenAIRE

    Zhang, Yuan; Chan, Jessica F.; Cummins, Carolyn L.

    2009-01-01

    Atherosclerosis is a disease characterized by excess cholesterol and inflammation in the blood vessels. The liver X receptors (alpha and beta) are members of the nuclear hormone receptor family that are activated by endogenous cholesterol metabolites. These receptors are widely expressed with a tissue distribution that includes the liver, intestine and macrophage. Upon activation, these receptors have been shown to increase reverse cholesterol transport from the macrophage back to the liver t...

  14. Membrane plasmalogen composition and cellular cholesterol regulation: a structure activity study

    OpenAIRE

    Su-Myat Khine K; Khan Mohamed A; Ritchie Shawn A; Jayasinghe Dushmanthi; Ma Hong; Ahiahonu Pearson WK; Mankidy Rishikesh; Wood Paul L; Goodenowe Dayan B

    2010-01-01

    Abstract Background Disrupted cholesterol regulation leading to increased circulating and membrane cholesterol levels is implicated in many age-related chronic diseases such as cardiovascular disease (CVD), Alzheimer's disease (AD), and cancer. In vitro and ex vivo cellular plasmalogen deficiency models have been shown to exhibit impaired intra- and extra-cellular processing of cholesterol. Furthermore, depleted brain plasmalogens have been implicated in AD and serum plasmalogen deficiencies ...

  15. RIP140 contributes to foam cell formation and atherosclerosis by regulating cholesterol homeostasis in macrophages

    OpenAIRE

    Lin, Yi-Wei; Liu, Pu-Ste; Adhikari, Neeta; Jennifer L Hall; Wei, Li-Na

    2014-01-01

    Atherosclerosis, a syndrome with abnormal arterial walls, is one of the major causes that lead to the development of various cardiovascular diseases. The key initiator of atherosclerosis is cholesterol accumulation. The uncontrolled cholesterol deposition, mainly involving low-density lipoprotein (LDL), causes atheroma plaque formation, which initiates chronic inflammation due to the recruitment of inflammatory cells such as macrophages. Macrophages scavenge excess peripheral cholesterol and ...

  16. Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection

    OpenAIRE

    See Hoe, Louise E; Schilling, Jan M.; Tarbit, Emiri; Kiessling, Can J.; Busija, Anna R.; Niesman, Ingrid R.; Du Toit, Eugene; Ashton, Kevin J; Roth, David M.; John P. Headrick; Patel, Hemal H.; Peart, Jason N.

    2014-01-01

    Cholesterol-rich caveolar microdomains and associated caveolins influence sarcolemmal ion channel and receptor function and protective stress signaling. However, the importance of membrane cholesterol content to cardiovascular function and myocardial responses to ischemia-reperfusion (I/R) and cardioprotective stimuli are unclear. We assessed the effects of graded cholesterol depletion with methyl-β-cyclodextrin (MβCD) and lifelong knockout (KO) or overexpression (OE) of caveolin-3 (Cav-3) on...

  17. Blood glucose may be an alternative to cholesterol in CVD risk prediction charts

    OpenAIRE

    Braun, Julia; Bopp, Matthias; Faeh, David

    2013-01-01

    Background Established risk models for the prediction of cardiovascular disease (CVD) include blood pressure, smoking and cholesterol parameters. The use of total cholesterol for CVD risk prediction has been questioned, particularly for primary prevention. We evaluated whether glucose could be used instead of total cholesterol for prediction of fatal CVD using data with long follow-up. Methods We followed-up 6,095 men and women aged ≥16 years who participated 1977-79 in a community based heal...

  18. The impact of a carbon nanotube on the cholesterol domain localized on a protein surface

    CERN Document Server

    Gburski, Zygmunt; Raczynski, Przemyslaw; 10.1016/j.ssc.2009.12.005

    2011-01-01

    The influence of a single walled carbon nanotube on the structure of a cholesterol cluster (domain) developed over the surface of the endothelial protein 1LQV has been investigated using the classical molecular dynamics (MD) simulation technique. We have observed a substantial impact of carbon nanotube on the arrangement of the cholesterol domain. The carbon nanotube can drag out cholesterol molecules, remarkable reducing the volume of the domain settled down on the protein.

  19. Comparative effects of hawthorn (Crataegus pinnatifida Bunge) pectin and pectin hydrolyzates on the cholesterol homeostasis of hamsters fed high-cholesterol diets.

    Science.gov (United States)

    Zhu, Ru-Gang; Sun, Yan-Di; Li, Tuo-Ping; Chen, Gang; Peng, Xue; Duan, Wen-Bin; Zheng, Zheng-Zheng; Shi, Shu-Lei; Xu, Jing-Guo; Liu, Yan-Hua; Jin, Xiao-Yi

    2015-08-01

    This study aims to compare the effects of feeding haw pectin (HP), haw pectin hydrolyzates (HPH), and haw pectin pentasaccharide (HPPS) on the cholesterol metabolism of hypercholesterolemic hamsters induced by high-cholesterol diets. The animals were fed a standard diet (SD), high-cholesterol diet (HCD), or HCD plus HP, HPH, or HPPS at a dose of 300mg/kg body weight for 4weeks. Results showed that HPPS was more effective than HP and HPH in decreasing the body weight gain (by 38.2%), liver weight (by 16.4%), and plasma and hepatic total cholesterol (TC; by 23.6% and 27.3%, respectively) of hamsters. In addition, the bile acid levels in the feces were significantly higher by 39.8% and 132.8% in the HPH and HPPS groups than in the HCD group. Such changes were not noted in the HP group. However, the HP group had higher cholesterol excretion capacities than the HPH and HPPS groups by inhibiting cholesterol absorption in the diet, with a 21.7% increase in TC excretion and a 31.1% decrease in TC absorption. Thus, HPPS could be a promising anti-atherogenic dietary ingredient for the development of functional food to improve cholesterol metabolism. PMID:26070415

  20. Combined effect of Lactobacillus acidophilus and β-cyclodextrin on serum cholesterol in pigs.

    Science.gov (United States)

    Alonso, L; Fontecha, J; Cuesta, P

    2016-01-14

    A total of twenty-four Yorkshire gilt pigs of 6-7 weeks of age were used in a 2×2 factorial experiment to determine the individual and combined effects of the inclusion of two dietary factors (cholesterol rich, 3% β-cyclodextrin (BCD) and Lactobacillus acidophilus cultures) on total cholesterol and LDL-cholesterol levels in blood serum. Pigs were assigned randomly to treatment groups (n 6). Total serum cholesterol concentrations decreased after 3 weeks in all the experimental treatment groups, including diets with BCD, L. acidophilus or both. Similar trends were observed for serum LDL-cholesterol concentrations among the experimental treatments. No statistically significant differences from the control group were observed in either total serum cholesterol or LDL-cholesterol concentrations (Psterile milk. The combined treatment group exhibited 17·9% lower total serum cholesterol concentration after 3 weeks. Similar significant differences were observed when comparing the combined effect experimental group with the control group after 3 weeks. The combined treatment group exhibited 27·9% lower serum LDL-cholesterol concentrations. PMID:26467089

  1. Viability and cholesterol uptake by Streptococcus thermophilus cultures in artificial git fluids

    Directory of Open Access Journals (Sweden)

    Małgorzata Ziarno

    2010-03-01

    Full Text Available Background. Streptococcus thermophilus is traditionally used in association with Lb. delbrueckii subsp. bulgaricus as a starter culture for the production of yoghurt. Some researchers have indicated that S. thermophilus may provide additional health benefits, for example it may reduce cholesterol levels. The aim of this study was to in vitro evaluate the cholesterol uptake and the viability of S. thermophilus isolates in artificial GIT environments. Material and methods. Twelve isolates of S. thermophilus were cultured in artificial gastric fluid (with pepsin added and in artificial duodenal fluid (with the enzyme complex added, and in M17 broth containing cholesterol at an initial concentration of 600 µg/mL, as well as in M17 broth without cholesterol. Immediately after the adding of bacteria inoculums and at the end of experiment, the concentration of cholesterol and the number of bacteria were measured. Results. S. thermophilus did not remove statistically significant amounts of cholesterol from artificial gastric fluid. The isolates showed the ability to uptake cholesterol from M17 broth and artificial duodenal fluid, and the degree of cholesterol uptake depended on the isolate. All isolates of S. thermophilus remove much more cholesterol from M17 broth than from artificial duodenal fluid. All S. thermophilus isolates had worse survival in artificial gastric or duodenal fluids than in M17 broth. Conclusions. The ability of S. thermophilus cells to survive in artificial gastric fluid and artificial duodenal fluid varied according to the isolates.

  2. Development and partial metabolic characterization of a dietary cholesterol-resistant colony of rabbits

    International Nuclear Information System (INIS)

    A colony of New Zealand white rabbits has been developed which, when fed a cholesterol-supplemented diet, exhibit unusual resistance to hypercholesterolemia and atherosclerosis, disorders usually observed in normal cholesterol-fed rabbits. When resistant rabbits (RT) were fed a normal low cholesterol diet (ND), their plasma lipoprotein patterns were significantly different from those of normal rabbits (NR) fed the same diet. The low density lipoprotein cholesterol (LDL-c)/high density lipoprotein cholesterol (HDL-c) ratio and LDL-c/very low density lipoprotein cholesterol (VLDL-c) ratio were lower in the resistant rabbits. The hydrated density of HDL of the normal-responsive rabbits was greater than that of the resistant rabbits. LDL from resistant rabbits contained a lower proportion of esterified cholesterol and protein than LDL from normal rabbits. Peripheral mononuclear cells from resistant rabbits bound about 30% more 125I-labeled rabbit LDL than mononuclear cells from normal rabbits. These results demonstrate that the plasma cholesterol levels of these animals is at least partly under genetic control and that compositional differences exist between the major plasma lipoprotein classes of normal and resistant rabbits even during the ingestion of low-cholesterol diet. The results indicate that at least a part of the difference in the cholesterolemic responses between the two rabbit groups is due to an enhanced LDL uptake by the mononuclear cells, and presumably by other somatic cells of the resistant group

  3. Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism.

    Science.gov (United States)

    Briand, François; Mayoux, Eric; Brousseau, Emmanuel; Burr, Noémie; Urbain, Isabelle; Costard, Clément; Mark, Michael; Sulpice, Thierry

    2016-07-01

    In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly reduced fasting blood glucose by 18%, with significant increase in fasting plasma LDL cholesterol, free fatty acids, and total ketone bodies by 25, 49, and 116%, respectively. In fasting conditions, glycogen hepatic levels were further reduced by 84% with empagliflozin, while 3-hydroxy-3-methylglutaryl-CoA reductase activity and total cholesterol hepatic levels were 31 and 10% higher, respectively (both P empagliflozin. Importantly, none of these parameters were changed by empagliflozin in fed conditions. Empagliflozin significantly reduced the catabolism of (3)H-cholesteryl oleate-labeled LDL injected intravenously by 20%, indicating that empagliflozin raises LDL levels through reduced catabolism. Unexpectedly, empagliflozin also reduced intestinal cholesterol absorption in vivo, which led to a significant increase in LDL- and macrophage-derived cholesterol fecal excretion (both P empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels. Interestingly, empagliflozin also reduces intestinal cholesterol absorption, which in turn promotes LDL- and macrophage-derived cholesterol fecal excretion. PMID:27207551

  4. Detectors for evaluating the cellular landscape of sphingomyelin- and cholesterol-rich membrane domains.

    Science.gov (United States)

    Kishimoto, Takuma; Ishitsuka, Reiko; Kobayashi, Toshihide

    2016-08-01

    Although sphingomyelin and cholesterol are major lipids of mammalian cells, the detailed distribution of these lipids in cellular membranes remains still obscure. However, the recent development of protein probes that specifically bind sphingomyelin and/or cholesterol provides new information about the landscape of the lipid domains that are enriched with sphingomyelin or cholesterol or both. Here, we critically summarize the tools to study distribution and dynamics of sphingomyelin and cholesterol. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID:26993577

  5. Luminol electrochemiluminescence for the analysis of active cholesterol at the plasma membrane in single mammalian cells.

    Science.gov (United States)

    Ma, Guangzhong; Zhou, Junyu; Tian, Chunxiu; Jiang, Dechen; Fang, Danjun; Chen, Hongyuan

    2013-04-16

    A luminol electrochemiluminescence assay was reported to analyze active cholesterol at the plasma membrane in single mammalian cells. The cellular membrane cholesterol was activated by the exposure of the cells to low ionic strength buffer or the inhibition of intracellular acyl-coA/cholesterol acyltransferase (ACAT). The active membrane cholesterol was reacted with cholesterol oxidase in the solution to generate a peak concentration of hydrogen peroxide on the electrode surface, which induced a measurable luminol electrochemiluminescence. Further treatment of the active cells with mevastatin decreased the active membrane cholesterol resulting in a drop in luminance. No change in the intracellular calcium was observed in the presence of luminol and voltage, which indicated that our analysis process might not interrupt the intracellular cholesterol trafficking. Single cell analysis was performed by placing a pinhole below the electrode so that only one cell was exposed to the photomultiplier tube (PMT). Twelve single cells were analyzed individually, and a large deviation on luminance ratio observed exhibited the cell heterogeneity on the active membrane cholesterol. The smaller deviation on ACAT/HMGCoA inhibited cells than ACAT inhibited cells suggested different inhibition efficiency for sandoz 58035 and mevastatin. The new information obtained from single cell analysis might provide a new insight on the study of intracellular cholesterol trafficking. PMID:23527944

  6. Cholesterol metabolism: A review of how ageing disrupts the biological mechanisms responsible for its regulation.

    Science.gov (United States)

    Morgan, A E; Mooney, K M; Wilkinson, S J; Pickles, N A; Mc Auley, M T

    2016-05-01

    Cholesterol plays a vital role in the human body as a precursor of steroid hormones and bile acids, in addition to providing structure to cell membranes. Whole body cholesterol metabolism is maintained by a highly coordinated balancing act between cholesterol ingestion, synthesis, absorption, and excretion. The aim of this review is to discuss how ageing interacts with these processes. Firstly, we will present an overview of cholesterol metabolism. Following this, we discuss how the biological mechanisms which underpin cholesterol metabolism are effected by ageing. Included in this discussion are lipoprotein dynamics, cholesterol absorption/synthesis and the enterohepatic circulation/synthesis of bile acids. Moreover, we discuss the role of oxidative stress in the pathological progression of atherosclerosis and also discuss how cholesterol biosynthesis is effected by both the mammalian target of rapamycin and sirtuin pathways. Next, we examine how diet and alterations to the gut microbiome can be used to mitigate the impact ageing has on cholesterol metabolism. We conclude by discussing how mathematical models of cholesterol metabolism can be used to identify therapeutic interventions. PMID:27045039

  7. Kinetics of solubilization with Triton X-100 of egg-yolk lecithin bilayers containing cholesterol

    CERN Document Server

    Hobai, S

    2001-01-01

    The titration solubilization of multilamellar egg-yolk lecithin liposomes (MLV-EYL) with Triton X-100 was studied by rectangular optical diffusimetric measurements as a function of cholesterol (Chol) concentration. It was determinated the variation of optic percentage diffu-sion (per mmol surfactant), DDif%/mmol TX-100, in the course of solubilization of MLV-EYL-Chol system with TX-100 10mM. The statistical analysis of the titration curves can reveal the contribution of cholesterol to the stability of phospholipid bilayer membranes. The solubilization of the lecithin-cholesterol mixtures, with a high cholesterol content, much more bile salt requires.

  8. Possible Domain Formation In PE/PC Bilayers Containing High Cholesterol

    Science.gov (United States)

    Hein, Matthew; Hussain, Fazle; Huang, Juyang

    2015-03-01

    Cholesterol is a significant component of animal cell membranes, and its presence has the effects of not only adding rigidity to the lipid bilayer, but also leading to the formation of lipid domains. Two other lipids of interest are phosphatidylethanolamine (PE), which constitutes about 45 percent of the phospholipids found in human nervous tissues, and phosphatidylcholine (PC), which is found in every cell of the human body. The maximum solubility of cholesterol is the highest mole fraction of cholesterol that the lipid bilayer can retain, at which point cholesterol begins to precipitate out to form cholesterol monohydrate crystals. We have measured the maximum solubility of cholesterol in mixtures of 16:0-18:1PE and 16:0-18:1PC using a new light scattering technique, which utilizes the anisotropic nature of light scattering by cholesterol crystals. This new method is highly accurate and reproducible. Our results show that the maximum solubility of cholesterol increases linearly as a function of the molar ratio POPC/(POPE+POPC), which suggests possible domain formation in mixtures of PE and PC containing maximum amount of cholesterol.

  9. Effect of cholesterol on the biophysical and physiological properties of a clinical pulmonary surfactant.

    Science.gov (United States)

    Keating, Eleonora; Rahman, Luna; Francis, James; Petersen, Anne; Possmayer, Fred; Veldhuizen, Ruud; Petersen, Nils O

    2007-08-15

    Pulmonary surfactant is a complex mixture of lipids and proteins that forms a surface-active film at the air-water interface of alveoli capable of reducing surface tension to near 0 mN/m. The role of cholesterol, the major neutral lipid component of pulmonary surfactant, remains uncertain. We studied the physiological effect of cholesterol by monitoring blood oxygenation levels of surfactant-deficient rats treated or not treated with bovine lipid extract surfactant (BLES) containing zero or physiological amounts of cholesterol. Our results indicate no significant difference between BLES and BLES containing cholesterol immediately after treatment; however, during ventilation, BLES-treated animals maintained higher PaO2 values compared to BLES+cholesterol-treated animals. We used a captive bubble tensiometer to show that physiological amounts of cholesterol do not have a detrimental effect on the surface activity of BLES at 37 degrees C. The effect of cholesterol on topography and lateral organization of BLES Langmuir-Blodgett films was also investigated using atomic force microscopy. Our data indicate that cholesterol induces the formation of domains within liquid-ordered domains (Lo). We used time-of-flight-secondary ion mass spectrometry and principal component analysis to show that cholesterol is concentrated in the Lo phase, where it induces structural changes. PMID:17526587

  10. Overexpression of Cholesterol 7α-hydroxylase promotes hepatic bile acid synthesis and secretion and maintains cholesterol homeostasis

    OpenAIRE

    Li, Tiangang; Matozel, Michelle; Boehme, Shannon; Kong, Bo; Nilsson, Lisa-Mari; Guo, Grace; Ellis, Ewa; Chiang, John Y. L.

    2011-01-01

    We reported previously that mice overexpressing Cyp7a1 (Cyp7a1-tg) are protected against high fat diet-induced hypercholesterolemia, obesity and insulin resistance (1). Here we investigated the underlying mechanism of bile acid signaling in maintaining cholesterol homeostasis in Cyp7a1-tg mice. Cyp7a1-tg mice had 2-fold higher Cyp7a1 activity and bile acid pool than wild type mice. Gallbladder bile acid composition changed from predominantly cholic acid (57%) in wild type to chenodeoxycholic ...

  11. LDL cholesterol still a problem in old age?

    DEFF Research Database (Denmark)

    Postmus, Iris; Deelen, Joris; Sedaghat, Sanaz;

    2015-01-01

    BACKGROUND: Observational studies in older subjects have shown no or inverse associations between cholesterol levels and mortality. However, in old age plasma low-density lipoprotein cholesterol (LDL-C) may not reflect the lifetime level due to reverse causality, and hence the risk may be...... Leiden 85-plus study (n = 316) and the Rotterdam Study (n = 4035). We assessed the association between the LDL GRS and LDL-C levels, chronological age, familial longevity and mortality. RESULTS: Up to 90 years of age, in each age stratum individuals with high LDL GRS had higher LDL-C levels (P = 0.010 to...... P = 1.1 x 10-16). The frequency of LDL-increasing alleles decreased with increasing age [β = -0.021 (SE = 0.01) per year, P = 0.018]. Moreover, individuals with a genetic predisposition for longevity had significantly lower LDL GRS compared with age-matched individuals of the general population [LLS...

  12. Impact of prescription size on statin adherence and cholesterol levels

    Directory of Open Access Journals (Sweden)

    Mehler Phillip S

    2007-10-01

    Full Text Available Abstract Background Therapy with 3-Hydroxy-3-methylglutaryl Co-enzyme A reductase inhibitors (statins improve outcomes in a broad spectrum of patients with hyperlipidemia. However, effective therapy requires ongoing medication adherence; restrictive pharmacy policies may represent a barrier to successful adherence, particularly among vulnerable patients. In this study we sought to assess the relationship between the quantity of statin dispensed by the pharmacy with patient adherence and total cholesterol. Methods We analyzed a cohort of 3,386 patients receiving more than one fill of statin medications through an integrated, inner-city health care system between January 1, 2000 and December 31, 2002. Our measure of adherence was days of drug acquisition divided by days in the study for each patient, with adequate adherence defined as ≥ 80%. Log-binomial regression was used to determine the relative risk of various factors, including prescription size, on adherence. We also assessed the relationship between adherence and total cholesterol using multiple linear regression. Results After controlling for age, gender, race, co-payment, comorbidities, and insurance status, patients who obtained a majority of fills as 60-day supply compared with 30-day supply were more likely to be adherent to their statin medications (RR 1.41, 95% CI 1.28–1.55, P Conclusion In a healthcare system serving predominantly indigent patients, the provision of a greater quantity of statin medication at each prescription fill contributes to improved adherence and greater drug effectiveness.

  13. Protein and cholesterol content of Araucana chicken eggs.

    Science.gov (United States)

    Somes, R G; Francis, P V; Tlustohowicz, J J

    1977-09-01

    Comparative data collected over two years are presented which refute the popular press claims that blue-shelled eggs of Araucana chickens have higher protein levels and lower cholesterol levels than market eggs. These comparisons were made between the eggs from the strains of Araucanas and those of White Leghorns and Sex-links. None of the differences found between test groups in % protein/g. albumen and % protein/g. yolk were shown to be consistently related to any one test group type. However, all Araucana test groups were significantly (P less than .01) lower in their total egg protein content than either control group by from 2.8--6.5%. This lower total protein content was the result of a consistent increase in the yolk/albumen ratio of the Araucana eggs over the market eggs. The Araucana eggs were consistently higher in their cholesterol levels on a mg./g. yolk basis than either of the market eggs. These increased concentrattions ranged from 2.0--6.9%. PMID:564510

  14. Decreased number of interstitial cells of Cajal play an important role in the declined intestinal transit during cholesterol gallstone formation in guinea pigs fed on high cholesterol diet

    OpenAIRE

    Fan, Ying; Wu, Shuo-Dong; Fu, Bei-Bei; Weng, Chao; Wang, Xin-Peng

    2014-01-01

    To study the changes of interstitial cells of Cajal (ICCs) and expression of c-kt and scf mRNA in terminal ileum tissue during cholesterol gallstone formation in guinea pigs fed on high cholesterol diet, forty guinea pigs were divided into the gallstone group and the control group. The animals in the gallstone group were fed on a high cholesterol diet (HCD), while those in the control group fed on a standard diet (StD). The guinea pigs were sacrificed at the 8th week. The expression of c-kit ...

  15. Effects of different fibre sources and fat addition on cholesterol and cholesterol-related lipids in blood serum, bile and body tissues of growing pigs.

    Science.gov (United States)

    Kreuzer, M; Hanneken, H; Wittmann, M; Gerdemann, M M; Machmuller, A

    2002-04-01

    Knowledge is limited on the efficacy of hindgut-fermentable dietary fibre to reduce blood, bile and body tissue cholesterol levels. In three experiments with growing pigs the effects of different kinds and levels of bacterially fermentable fibre (BFS) on cholesterol metabolism were examined. Various diets calculated to have similar contents of metabolizable energy were supplied for complete fattening periods. In the first experiment, a stepwise increase from 12 to 20% BFS was performed by supplementing diets with fermentable fibre from sugar beet pulp (modelling hemicelluloses and pectin). Beet pulp, rye bran (modelling cellulose) and citrus pulp (pectin) were offered either independently or in a mixture in the second experiment. These diets were opposed to rations characterized in carbohydrate type by starch either mostly non-resistant (cassava) or partly resistant (maize) to small intestinal digestion. The third experiment was planned to explore the interactions of BFS from citrus pulp with fat either through additional coconut oil/palm kernel oil blend or full-fat soybeans. In all experiments the increase of the BFS content was associated with a constant (cellulose) or decreasing (hemicelluloses, pectin) dietary proportion of non-digestible fibre. In experiment 1 an inverse dose-response relationship between BFS content and cholesterol in blood serum and adipose tissue as well as bile acid concentration in bile was noted while muscle cholesterol did not respond. In experiment 2 the ingredients characterized by cellulose and hemicelluloses/pectin reduced cholesterol-related traits relative to the low-BFS-high-starch controls whereas, except in adipose tissue cholesterol content, the pectinous ingredient had the opposite effect. However, the changes in serum cholesterol mainly affected HDL and not LDL cholesterol. Adipose tissue cholesterol also was slightly lower with partly resistant starch compared to non-resistant starch in the diet. Experiment 3 showed that

  16. Cholesterol and bile acids regulate cholesterol 7 alpha-hydroxylase expression at the transcriptional level in culture and in transgenic mice.

    OpenAIRE

    Ramirez, M.I.; Karaoglu, D; Haro, D; Barillas, C; Bashirzadeh, R; Gil, G.

    1994-01-01

    Cholesterol 7 alpha-hydroxylase (7 alpha-hydroxylase) is the rate-limiting enzyme in bile acid biosynthesis. It is subject to a feedback control, whereby high levels of bile acids suppress its activity, and cholesterol exerts a positive control. It has been suggested that posttranscriptional control plays a major part in that regulation. We have studied the mechanisms by which cholesterol and bile acids regulate expression of the 7 alpha-hydroxylase gene and found it to be solely at the trans...

  17. Eimeria bovis infection modulates endothelial host cell cholesterol metabolism for successful replication.

    Science.gov (United States)

    Hamid, Penny H; Hirzmann, Joerg; Kerner, Katharina; Gimpl, Gerald; Lochnit, Guenter; Hermosilla, Carlos R; Taubert, Anja

    2015-01-01

    During first merogony Eimeria bovis forms large macromeronts in endothelial host cells containing >120 000 merozoites I. During multiplication, large amounts of cholesterol are indispensable for the enormous offspring membrane production. Cholesterol auxotrophy was proven for other apicomplexan parasites. Consequently they scavenge cholesterol from their host cell apparently in a parasite-specific manner. We here analyzed the influence of E. bovis infection on endothelial host cell cholesterol metabolism and found considerable differences to other coccidian parasites. Overall, free cholesterol significantly accumulated in E. bovis infected host cells. Furthermore, a striking increase of lipid droplet formation was observed within immature macromeronts. Artificial host cell lipid droplet enrichment significantly improved E. bovis merozoite I production confirming the key role of lipid droplet contents for optimal parasite proliferation. The transcription of several genes being involved in both, cholesterol de novo biosynthesis and low density lipoprotein-(LDL) mediated uptake, was significantly up-regulated at a time in infected cells suggesting a simultaneous exploitation of these two cholesterol acquisition pathways. E. bovis scavenges LDL-derived cholesterol apparently through significantly increased levels of surface LDL receptor abundance and LDL binding to infected cells. Consequently, LDL supplementation significantly improved parasite replication. The up-regulation of the oxidized LDL receptor 1 furthermore identified this scavenger receptor as a key molecule in parasite-triggered LDL uptake. Moreover, cellular cholesterol processing was altered in infected cells as indicated by up-regulation of cholesterol-25-hydroxylase and sterol O-acyltransferase. Overall, these results show that E. bovis considerably exploits the host cell cholesterol metabolism to guarantee its massive intracellular growth and replication. PMID:26395984

  18. PPARγ regulates the expression of cholesterol metabolism genes in alveolar macrophages

    International Nuclear Information System (INIS)

    Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear transcription factor involved in lipid metabolism that is constitutively expressed in the alveolar macrophages of healthy individuals. PPARγ has recently been implicated in the catabolism of surfactant by alveolar macrophages, specifically the cholesterol component of surfactant while the mechanism remains unclear. Studies from other tissue macrophages have shown that PPARγ regulates cholesterol influx, efflux, and metabolism. PPARγ promotes cholesterol efflux through the liver X receptor-alpha (LXRα) and ATP-binding cassette G1 (ABCG1). We have recently shown that macrophage-specific PPARγ knockout (PPARγ KO) mice accumulate cholesterol-laden alveolar macrophages that exhibit decreased expression of LXRα and ABCG1 and reduced cholesterol efflux. We hypothesized that in addition to the dysregulation of these cholesterol efflux genes, the expression of genes involved in cholesterol synthesis and influx was also dysregulated and that replacement of PPARγ would restore regulation of these genes. To investigate this hypothesis, we have utilized a Lentivirus expression system (Lenti-PPARγ) to restore PPARγ expression in the alveolar macrophages of PPARγ KO mice. Our results show that the alveolar macrophages of PPARγ KO mice have decreased expression of key cholesterol synthesis genes and increased expression of cholesterol receptors CD36 and scavenger receptor A-I (SRA-I). The replacement of PPARγ (1) induced transcription of LXRα and ABCG1; (2) corrected suppressed expression of cholesterol synthesis genes; and (3) enhanced the expression of scavenger receptors CD36. These results suggest that PPARγ regulates cholesterol metabolism in alveolar macrophages.

  19. The cholesterol-dependent cytolysin family of gram-positive bacterial toxins.

    Science.gov (United States)

    Heuck, Alejandro P; Moe, Paul C; Johnson, Benjamin B

    2010-01-01

    The cholesterol-dependent cytolysins (CDCs) are a family of beta-barrel pore-forming toxins secreted by Gram-positive bacteria. These toxins are produced as water-soluble monomeric proteins that after binding to the target cell oligomerize on the membrane surface forming a ring-like pre-pore complex, and finally insert a large beta-barrel into the membrane (about 250 A in diameter). Formation of such a large transmembrane structure requires multiple and coordinated conformational changes. The presence of cholesterol in the target membrane is absolutely required for pore-formation, and therefore it was long thought that cholesterol was the cellular receptor for these toxins. However, not all the CDCs require cholesterol for binding. Intermedilysin, secreted by Streptoccocus intermedius only binds to membranes containing a protein receptor, but forms pores only if the membrane contains sufficient cholesterol. In contrast, perfringolysin O, secreted by Clostridium perfringens, only binds to membranes containing substantial amounts of cholesterol. The mechanisms by which cholesterol regulates the cytolytic activity of the CDCs are not understood at the molecular level. The C-terminus of perfringolysin O is involved in cholesterol recognition, and changes in the conformation of the loops located at the distal tip of this domain affect the toxin-membrane interactions. At the same time, the distribution of cholesterol in the membrane can modulate toxin binding. Recent studies support the concept that there is a dynamic interplay between the cholesterol-binding domain of the CDCs and the excess of cholesterol molecules in the target membrane. PMID:20213558

  20. DRIED BLOOD/SERUM SPOT TOTAL CHOLESTEROL ESTIMATION AS AN ALTERNATIVE TO FRESH SERUM TOTAL CHOLESTEROL: AN ANSWER OR A QUESTION IN ITSELF?

    OpenAIRE

    Pushpa,; Raghunath; Nimisha

    2015-01-01

    INTRODUCTION: Surveillance for risk factors of heart diseases, like increased blood sugar, cholesterol becomes difficult in places with inadequate lab facilities due to difficulty in sample collection, transportation and processing. Feasibility of using dried blood/seru m spots in such situations can be thought of as an alternative to fresh serum total cholesterol, as sample collection does not require much expertise. AIM: The aim of this study is to determine whether ...