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  1. 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.

  2. 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.

  3. 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

  4. Effect of cellular cholesterol depletion on rabies virus infection.

    Science.gov (United States)

    Hotta, Kozue; Bazartseren, Boldbarrtar; Kaku, Yoshihiro; Noguchi, Akira; Okutani, Akiko; Inoue, Satoshi; Yamada, Akio

    2009-01-01

    Although there are several reports on candidates for rabies virus (RABV) receptor, possible roles played by these receptor candidates in determination of highly neurotropic nature of RABV have not been well understood. Since these candidate receptors for RABV were reported to be frequently associated with cholesterol-rich microdomains characterized by lipid rafts and caveolae structures, we attempted to determine whether the disturbance of microdomains caused by the cholesterol depletion showed any effects on RABV infection. When the cellular cholesterol was depleted by methyl-beta-cyclodextrin (MBCD) treatment, increase in RABV adsorption and infection, but not multiplication rather than suppression was observed in both BHK-21 and HEp-2 cells. These effects exerted by MBCD treatment on RABV infection could be reversed by cholesterol reconstitution. These results suggest that RABV enters BHK-21 or HEp-2 cells through ports of entry other than those located on cholesterol-rich microdomains and raise the possibility that RABV uses different mechanisms to enter the non-neuronal cells. PMID:19010362

  5. Low HDL cholesterol, aggression and altered central serotonergic activity.

    Science.gov (United States)

    Buydens-Branchey, L; Branchey, M; Hudson, J; Fergeson, P

    2000-03-01

    Many studies support a significant relation between low cholesterol levels and poor impulse, aggression and mood control. Evidence exists also for a causal link between low brain serotonin (5-HT) activity and these behaviors. Mechanisms linking cholesterol and hostile or self-destructive behavior are unknown, but it has been suggested that low cholesterol influences 5-HT function. This study was designed to explore the relationship between plasma cholesterol, measures of impulsivity and aggression, and indices of 5-HT function in personality disordered cocaine addicts. Thirty-eight hospitalized male patients (age 36.8+/-7.1) were assessed with the DSM-III-R, the Buss-Durkee Hostility Inventory (BDHI), the Barratt Impulsiveness Scale (BIS) and the Brown-Goodwin Assessment for Life History of Aggression. Fasting basal cholesterol (total, LDL and HDL) was determined 2 weeks after cocaine discontinuation. On the same day 5-HT function was assessed by neuroendocrine (cortisol and prolactin) and psychological (NIMH and 'high' self-rating scales) responses following meta-chlorophenylpiperazine (m-CPP) challenges. Reduced neuroendocrine responses, 'high' feelings and increased 'activation-euphoria' following m-CPP have been interpreted as indicating 5-HT alterations in a variety of psychiatric conditions. Significantly lower levels of HDL cholesterol were found in patients who had a history of aggression (P=0.005). Lower levels of HDL cholesterol were also found to be significantly associated with more intense 'high' and 'activation-euphoria' responses as well as with blunted cortisol responses to m-CPP (P=0.033, P=0.025 and P=0.018, respectively). This study gives further support to existing evidence indicating that in some individuals, the probability of exhibiting impulsive and violent behaviors may be increased when cholesterol is low. It also suggests that low cholesterol and alterations in 5-HT activity may be causally related.

  6. Cholesterol depletion of enterocytes. Effect on the Golgi complex and apical membrane trafficking

    DEFF Research Database (Denmark)

    Hansen, Gert Helge; Niels-Christiansen, L L; Thorsen, Evy;

    2000-01-01

    Intestinal brush border enzymes, including aminopeptidase N and sucrase-isomaltase, are associated with "rafts" (membrane microdomains rich in cholesterol and sphingoglycolipids). To assess the functional role of rafts in the present work, we studied the effect of cholesterol depletion on apical......-associated. Our results implicate the Golgi complex/trans-Golgi network in raft formation and suggest a close relationship between this event and apical membrane trafficking....

  7. 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.

  8. Altered cholesterol and fatty acid metabolism in Huntington disease.

    Science.gov (United States)

    Block, Robert C; Dorsey, E Ray; Beck, Christopher A; Brenna, J Thomas; Shoulson, Ira

    2010-01-01

    Huntington disease is an autosomal dominant neurodegenerative disorder characterized by behavioral abnormalities, cognitive decline, and involuntary movements that lead to a progressive decline in functional capacity, independence, and ultimately death. The pathophysiology of Huntington disease is linked to an expanded trinucleotide repeat of cytosine-adenine-guanine (CAG) in the IT-15 gene on chromosome 4. There is no disease-modifying treatment for Huntington disease, and novel pathophysiological insights and therapeutic strategies are needed. Lipids are vital to the health of the central nervous system, and research in animals and humans has revealed that cholesterol metabolism is disrupted in Huntington disease. This lipid dysregulation has been linked to specific actions of the mutant huntingtin on sterol regulatory element binding proteins. This results in lower cholesterol levels in affected areas of the brain with evidence that this depletion is pathologic. Huntington disease is also associated with a pattern of insulin resistance characterized by a catabolic state resulting in weight loss and a lower body mass index than individuals without Huntington disease. Insulin resistance appears to act as a metabolic stressor attending disease progression. The fish-derived omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have been examined in clinical trials of Huntington disease patients. Drugs that combat the dysregulated lipid milieu in Huntington disease may help treat this perplexing and catastrophic genetic disease.

  9. Alterations in plasma lecithin : cholesterol acyltransferase and myeloperoxidase in acute myocardial infarction: Implications for cardiac outcome

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Tietge, Uwe J. F.; Kwakernaak, Arjan J.; Dikkeschei, Bert D.; Perton, Frank; Tio, Rene A.

    2014-01-01

    Background: The cholesterol esterifying enzyme, lecithin: cholesterol acyltransferase (LCAT), plays a key role in HDL maturation and remodeling. Myeloperoxidase (MPO) may compromise LCAT enzymatic activity. We tested the extent to which plasma LCAT activity is altered in acute myocardial infarction

  10. Syntaxin and VAMP association with lipid rafts depends on cholesterol depletion in capacitating sperm cells.

    Science.gov (United States)

    Tsai, Pei-Shiue; De Vries, Klaas J; De Boer-Brouwer, Mieke; Garcia-Gil, Nuria; Van Gestel, Renske A; Colenbrander, Ben; Gadella, Bart M; Van Haeften, Theo

    2007-01-01

    Sperm cells represent a special exocytotic system since mature sperm cells contain only one large secretory vesicle, the acrosome, which fuses with the overlying plasma membrane during the fertilization process. Acrosomal exocytosis is believed to be regulated by activation of SNARE proteins. In this paper, we identified specific members of the SNARE protein family, i.e., the t-SNAREs syntaxin1 and 2, and the v-SNARE VAMP, present in boar sperm cells. Both syntaxins were predominantly found in the plasma membrane whereas v-SNAREs are mainly located in the outer acrosomal membrane of these cells. Under non-capacitating conditions both syntaxins and VAMP are scattered in well-defined punctate structures over the entire sperm head. Bicarbonate-induced in vitro activation in the presence of BSA causes a relocalization of these SNAREs to a more homogeneous distribution restricted to the apical ridge area of the sperm head, exactly matching the site of sperm zona binding and subsequent induced acrosomal exocytosis. This redistribution of syntaxin and VAMP depends on cholesterol depletion and closely resembles the previously reported redistribution of lipid raft marker proteins. Detergent-resistant membrane isolation and subsequent analysis shows that a significant proportion of syntaxin emerges in the detergent-resistant membrane (raft) fraction under such conditions, which is not the case under those conditions where cholesterol depletion is blocked. The v-SNARE VAMP displays a similar cholesterol depletion-dependent lateral and raft redistribution. Taken together, our results indicate that redistribution of syntaxin and VAMP during capacitation depends on association of these SNAREs with lipid rafts and that such a SNARE-raft association may be essential for spatial control of exocytosis and/or regulation of SNARE functioning.

  11. Inhibition of protein kinase C affects on mode of synaptic vesicle exocytosis due to cholesterol depletion

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, Alexey M., E-mail: fysio@rambler.ru; Zakyrjanova, Guzalija F., E-mail: guzik121192@mail.ru; Yakovleva, Anastasia A., E-mail: nastya1234qwer@mail.ru; Zefirov, Andrei L., E-mail: zefiroval@rambler.ru

    2015-01-02

    Highlights: • We examine the involvement of PKC in MCD induced synaptic vesicle exocytosis. • PKC inhibitor does not decrease the effect MCD on MEPP frequency. • PKC inhibitor prevents MCD induced FM1-43 unloading. • PKC activation may switch MCD induced exocytosis from kiss-and-run to a full mode. • Inhibition of phospholipase C does not lead to similar change in exocytosis. - Abstract: Previous studies demonstrated that depletion of membrane cholesterol by 10 mM methyl-beta-cyclodextrin (MCD) results in increased spontaneous exocytosis at both peripheral and central synapses. Here, we investigated the role of protein kinase C in the enhancement of spontaneous exocytosis at frog motor nerve terminals after cholesterol depletion using electrophysiological and optical methods. Inhibition of the protein kinase C by myristoylated peptide and chelerythrine chloride prevented MCD-induced increases in FM1-43 unloading, whereas the frequency of spontaneous postsynaptic events remained enhanced. The increase in FM1-43 unloading still could be observed if sulforhodamine 101 (the water soluble FM1-43 quencher that can pass through the fusion pore) was added to the extracellular solution. This suggests a possibility that exocytosis of synaptic vesicles under these conditions could occur through the kiss-and-run mechanism with the formation of a transient fusion pore. Inhibition of phospholipase C did not lead to similar change in MCD-induced exocytosis.

  12. FLIM studies of 22- and 25-NBD-cholesterol in living HEK293 cells: plasma membrane change induced by cholesterol depletion.

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    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

  13. Enzymatic assay of total cholesterol in serum or plasma by amperometric measurement of rate of oxygen depletion following saponification.

    Science.gov (United States)

    Kumar, A; Christian, G D

    1977-01-17

    A method for serum or plasma cholesterol assay involving amperometric measurement of the rate of oxygen depletion in the cholesterol oxidase-catalyzed oxidation of cholesterol is described. The hydrolysis of the serum cholesterol esters is accomplished by saponification of 50 mul of sample with 0.2 ml of ethanolic KOH (1.0 mol/1) containing 0.5% Triton X-100 for 5 min at 75 degrees C. The rate of oxygen consumption in a 25-mul aliquot of this is measured with a Clark electrode in a Beckman Glucose Analyzer and the assay takes about one minute after incubation; results are read digitally on the instrument. The analyzer cell contains 1 ml of 1 M phosphate buffer, pH 7.4, with 100 mg sodium cholate/100 ml and 0.1-0.2 U cholesterol oxidase.

  14. Impact of a chronic ingestion of radionuclides on cholesterol metabolism in the rat: example of depleted uranium and cesium 137

    International Nuclear Information System (INIS)

    Depleted uranium (DU) and cesium-137 (137Cs) are radionuclides spread in the environment due to industrial activities, incidents or accidents. This pollution sets a risk of human exposure to low levels of radiations through contaminated foodstuff. The impact of a chronic ingestion of DU or 137Cs on cholesterol metabolism in the liver and the brain has been studied. Indeed, cholesterol is crucial in physiology, being a component of cell membranes and a precursor to numerous molecules (bile acids...). Disruption of its metabolism is associated to many pathologies such as atherosclerosis or Alzheimer disease. Rats daily ingested a low level of DU or 137Cs over 9 months. For each radionuclide, a reference model (rats contaminated since adulthood) and a more sensitive model (hypercholesterolemic or contaminated since fetal life) were studied. The effects mainly consist of changes in gene expression or enzymatic activity of various actors of cholesterol metabolism. DU mainly affects one catabolism enzyme in both models, as well as membrane transporters and regulation factors. 137Cs mainly affects the storage enzyme in both models as well as catabolism enzymes, apolipoproteins, and regulation factors. No change in the plasma profile or in the tissue concentration of cholesterol (hepatic/cerebral) is recorded, whatever the model and the radionuclide. Thus, a chronic internal contamination with DU or 137Cs induces molecular modifications in cholesterol metabolism in the rat, without affecting its homeostasis or the general health status in all of our experimental models. (author)

  15. Hepatic steatosis in n-3 fatty acid depleted mice: focus on metabolic alterations related to tissue fatty acid composition

    Directory of Open Access Journals (Sweden)

    Malaisse WJ

    2008-12-01

    Full Text Available Abstract Background There are only few data relating the metabolic consequences of feeding diets very low in n-3 fatty acids. This experiment carried out in mice aims at studying the impact of dietary n-3 polyunsaturated fatty acids (PUFA depletion on hepatic metabolism. Results n-3 PUFA depletion leads to a significant decrease in body weight despite a similar caloric intake or adipose tissue weight. n-3 PUFA depleted mice exhibit hypercholesterolemia (total, HDL, and LDL cholesterol as well as an increase in hepatic cholesteryl ester and triglycerides content. Fatty acid pattern is profoundly modified in hepatic phospholipids and triglycerides. The decrease in tissue n-3/n-6 PUFA ratio correlates with steatosis. Hepatic mRNA content of key factors involved in lipid metabolism suggest a decreased lipogenesis (SREBP-1c, FAS, PPARγ, and an increased β-oxidation (CPT1, PPARα and PGC1α without modification of fatty acid esterification (DGAT2, GPAT1, secretion (MTTP or intracellular transport (L-FABP. Histological analysis reveals alterations of liver morphology, which can not be explained by inflammatory or oxidative stress. However, several proteins involved in the unfolded protein response are decreased in depleted mice. Conclusion n-3 PUFA depletion leads to important metabolic alterations in murine liver. Steatosis occurs through a mechanism independent of the shift between β-oxidation and lipogenesis. Moreover, long term n-3 PUFA depletion decreases the expression of factors involved in the unfolded protein response, suggesting a lower protection against endoplasmic reticulum stress in hepatocytes upon n-3 PUFA deficiency.

  16. Increased basolateral sorting of carcinoembryonic antigen in a polarized colon carcinoma cell line after cholesterol depletion-Implications for treatment of inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Robert Ehehalt; Markus Krautter; Martin Zorn; Richard Sparla; Joachim Fūllekrug; Hasan Kulaksiz; Wolfgang Stremmel

    2008-01-01

    AIM:To investigate a possible increase of basolateral expression of carcinoembryonic antigen(CEA)by interfering with the apical transport machinery,we studied the effect of cholesterol depletion on CEA sorting and secretion.METHODS:Cholesterol depletion was performed in polarized Caco-2 cells using Iovastatin and methyl-βcyclodextrin.RESULTS:We show that CEA is predominantly expressed and secreted at the apical surface.Reduction of the cholesterol level of the cell by 40%-50% with Iovastatin and methyl-β-cyclodextrin led to a significant change of the apical-to-basolateral transport ratio towards the basolateral membrane.CONCLUSION:As basolateral expression of CEA has been suggested to have anti-inflamatory properties,Cholesterol depletion of enterocytes might be a potential approach to influence the course of inflammatory bowel disease.

  17. Cholesterol Removal from Adult Skeletal Muscle impairs Excitation-Contraction Coupling and Aging reduces Caveolin-3 and alters the Expression of other Triadic Proteins

    Directory of Open Access Journals (Sweden)

    Genaro eBarrientos

    2015-04-01

    Full Text Available Cholesterol and caveolin are integral membrane components that modulate the function/location of many cellular proteins. Skeletal muscle fibers, which have unusually high cholesterol levels in transverse tubules, express the caveolin-3 isoform but its association with transverse tubules remains contentious. Cholesterol removal impairs excitation-contraction coupling in amphibian and mammalian fetal skeletal muscle fibers. Here, we show that treating single muscle fibers from adult mice with the cholesterol removing agent methyl-β-cyclodextrin decreased fiber cholesterol by 26%, altered the location pattern of caveolin-3 and of the voltage dependent calcium channel Cav1.1, and suppressed or reduced electrically evoked Ca2+ transients without affecting membrane integrity or causing sarcoplasmic reticulum calcium depletion. We found that transverse tubules from adult muscle and triad fractions that contain ~10% attached transverse tubules, but not sarcoplasmic reticulum membranes, contained caveolin-3 and Cav1.1; both proteins partitioned into detergent-resistant membrane fractions highly enriched in cholesterol. Aging entails significant deterioration of skeletal muscle function. We found that triad fractions from aged rats had similar cholesterol and RyR1 protein levels compared to triads from young rats, but had lower caveolin-3 and glyceraldehyde 3-phosphate dehydrogenase and increased Na+/K+-ATPase protein levels. Both triad fractions had comparable NADPH oxidase (NOX activity and protein content of NOX2 subunits (p47phox and gp91phox, implying that NOX activity does not increase during aging. These findings show that partial cholesterol removal impairs excitation-contraction coupling and alters caveolin-3 and Cav1.1 location pattern, and that aging reduces caveolin-3 protein content and modifies the expression of other triadic proteins. We discuss the possible implications of these findings for skeletal muscle function in young and aged

  18. Alterations in the homeostasis of phospholipids and cholesterol by antitumor alkylphospholipids

    Directory of Open Access Journals (Sweden)

    Segovia Josefa L

    2010-03-01

    biosynthesis as well as the receptor-mediated uptake of cholesterol. Thus, membrane-targeted alkylphospholipids exhibit a common mechanism of action through disruption of cholesterol homeostasis. The accumulation of cholesterol within the cell and the reduction in phosphatidylcholine and sphingomyelin biosyntheses certainly alter the ratio of choline-bearing phospholipids to cholesterol, which is critical for the integrity and functionality of specific membrane microdomains such as lipid rafts. Alkylphospholipid-induced alterations in lipid homeostasis with probable disturbance of the native membrane structure could well affect signaling processes vital to cell survival and growth.

  19. Influence of environmental enrichment and depleted uranium on behaviour, cholesterol and acetylcholine in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Lestaevel, P; Airault, F; Racine, R; Bensoussan, H; Dhieux, B; Delissen, O; Manens, L; Aigueperse, J; Voisin, P; Souidi, M

    2014-07-01

    Alzheimer's disease is associated with genetic risk factors, of which the apolipoprotein E (ApoE) is the most prevalent, and is affected by environmental factors that include education early in life and exposure to metals. The industrial and military use of depleted uranium (DU) resulted in an increase of its deposition in some areas and led to a possible environmental factor. The present study aims to ascertain the effects on the behaviour and the metabolism of cholesterol and acetylcholine of ApoE-/- mice exposed to enriched environment (EE) and exposed to DU (20 mg/L) for 14 weeks. Here we show that ApoE-/- mice were unaffected by the EE and their learning and memory were similar to those of the non-enriched ApoE-/- mice. ApoE-/- mice showed a significant decrease in total (-16 %) and free (-16 %) cholesterol in the entorhinal cortex in comparison to control wild-type mice. Whatever the housing conditions, the exposure to DU of ApoE-/- mice impaired working memory, but had no effect on anxiety-like behaviour, in comparison to control ApoE-/- mice. The exposure of ApoE-/- mice to DU also induced a trend toward higher total cholesterol content in the cerebral cortex (+15 %) compared to control ApoE-/- mice. In conclusion, these results demonstrate that enriched environment does not ameliorate neurobehaviour in ApoE-/- mice and that ApoE mutation induced specific effects on the brain cholesterol. These findings also suggested that DU exposure could modify the pathology in this ApoE model, with no influence of housing conditions. PMID:23749703

  20. 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...

  1. Guanidination of notexin alters its membrane-damaging activity in response to sphingomyelin and cholesterol

    Indian Academy of Sciences (India)

    Pei-Hsiu Kao; Yi-Ling Chiou; Shinne-Ren Lin; Long-Sen Chang

    2010-12-01

    To elucidate the contribution of phospholipase A2 (PLA2) activity of notexin to its ability to perturb membranes, comparative studies on the interaction of notexin and guanidinated notexin (Gu-notexin) with egg yolk phosphatidylcholine (EYPC), EYPC/egg yolk sphingomyelin (EYSM) and EYPC/EYSM/cholesterol vesicles were conducted. EYSM notably reduced the membrane-damaging activity of notexin against EYPC vesicles, but had an insignificant influence on that of Gu-notexin. Unlike the effects noted with notexin, inactivation of PLA2 activity by EDTA led to a reduction in the ability of Gu-notexin to induce EYPC/EYSM vesicle leakage and to increase Gu-notexin-induced membrane permeability of EYPC/EYSM/cholesterol vesicles. The geometrical arrangement of notexin and Gu-notexin in contact with either EYPC/EYSM vesicles or EYPC/EYSM/cholesterol vesicles differed. Moreover, global conformation of notexin and Gu-notexin differed in either Ca2+-bound or metal-free states. These results indicate that notexin and Gu-notexin could induce membrane permeability without the involvement of PLA2 activity, and suggest that guanidination alters the membrane-bound mode of notexin on damaging phospholipid vesicles containing sphingomyelin and cholesterol.

  2. Higher high density lipoprotein cholesterol associated with moderate alcohol consumption is not related to altered plasma lecithin : cholesterol acyltransferase and lipid transfer protein activity levels

    NARCIS (Netherlands)

    Riemens, SC; vanTol, A; Hoogenberg, K; vanGent, T; Scheek, LM; Sluiter, WJ; Dullaart, RPF

    1997-01-01

    Lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are important factors involved in HDL metabolism. Altered plasma activity levels of these factors could play a role in the increase in high density lipoprotein (HDL) choles

  3. 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...

  4. Sustained Epigenetic Drug Delivery Depletes Cholesterol-Sphingomyelin Rafts from Resistant Breast Cancer Cells, Influencing Biophysical Characteristics of Membrane Lipids.

    Science.gov (United States)

    Raghavan, Vijay; Vijayaraghavalu, Sivakumar; Peetla, Chiranjeevi; Yamada, Masayoshi; Morisada, Megan; Labhasetwar, Vinod

    2015-10-27

    Cell-membrane lipid composition can greatly influence biophysical properties of cell membranes, affecting various cellular functions. We previously showed that lipid synthesis becomes altered in the membranes of resistant breast cancer cells (MCF-7/ADR); they form a more rigid, hydrophobic lipid monolayer than do sensitive cell membranes (MCF-7). These changes in membrane lipids of resistant cells, attributed to epigenetic aberration, significantly affected drug transport and endocytic function, thus impacting the efficacy of anticancer drugs. The present study's objective was to determine the effects of the epigenetic drug, 5-aza-2'-deoxycytidine (DAC), delivered in sustained-release nanogels (DAC-NGs), on the composition and biophysical properties of membrane lipids of resistant cells. Resistant and sensitive cells were treated with DAC in solution (DAC-sol) or DAC-NGs, and cell-membrane lipids were isolated and analyzed for lipid composition and biophysical properties. In resistant cells, we found increased formation of cholesterol-sphingomyelin (CHOL-SM) rafts with culturing time, whereas DAC treatment reduced their formation. In general, the effect of DAC-NGs was greater in changing the lipid composition than with DAC-sol. DAC treatment also caused a rise in levels of certain phospholipids and neutral lipids known to increase membrane fluidity, while reducing the levels of certain lipids known to increase membrane rigidity. Isotherm data showed increased lipid membrane fluidity following DAC treatment, attributed to decrease levels of CHOL-SM rafts (lamellar beta [Lβ] structures or ordered gel) and a corresponding increase in lipids that form lamellar alpha-structures (Lα, liquid crystalline phase). Sensitive cells showed marginal or insignificant changes in lipid profile following DAC-treatment, suggesting that epigenetic changes affecting lipid biosynthesis are more specific to resistant cells. Since membrane fluidity plays a major role in drug transport

  5. Sustained Epigenetic Drug Delivery Depletes Cholesterol-Sphingomyelin Rafts from Resistant Breast Cancer Cells, Influencing Biophysical Characteristics of Membrane Lipids.

    Science.gov (United States)

    Raghavan, Vijay; Vijayaraghavalu, Sivakumar; Peetla, Chiranjeevi; Yamada, Masayoshi; Morisada, Megan; Labhasetwar, Vinod

    2015-10-27

    Cell-membrane lipid composition can greatly influence biophysical properties of cell membranes, affecting various cellular functions. We previously showed that lipid synthesis becomes altered in the membranes of resistant breast cancer cells (MCF-7/ADR); they form a more rigid, hydrophobic lipid monolayer than do sensitive cell membranes (MCF-7). These changes in membrane lipids of resistant cells, attributed to epigenetic aberration, significantly affected drug transport and endocytic function, thus impacting the efficacy of anticancer drugs. The present study's objective was to determine the effects of the epigenetic drug, 5-aza-2'-deoxycytidine (DAC), delivered in sustained-release nanogels (DAC-NGs), on the composition and biophysical properties of membrane lipids of resistant cells. Resistant and sensitive cells were treated with DAC in solution (DAC-sol) or DAC-NGs, and cell-membrane lipids were isolated and analyzed for lipid composition and biophysical properties. In resistant cells, we found increased formation of cholesterol-sphingomyelin (CHOL-SM) rafts with culturing time, whereas DAC treatment reduced their formation. In general, the effect of DAC-NGs was greater in changing the lipid composition than with DAC-sol. DAC treatment also caused a rise in levels of certain phospholipids and neutral lipids known to increase membrane fluidity, while reducing the levels of certain lipids known to increase membrane rigidity. Isotherm data showed increased lipid membrane fluidity following DAC treatment, attributed to decrease levels of CHOL-SM rafts (lamellar beta [Lβ] structures or ordered gel) and a corresponding increase in lipids that form lamellar alpha-structures (Lα, liquid crystalline phase). Sensitive cells showed marginal or insignificant changes in lipid profile following DAC-treatment, suggesting that epigenetic changes affecting lipid biosynthesis are more specific to resistant cells. Since membrane fluidity plays a major role in drug transport

  6. Cholesterol Depletion Reduces the Internalization of β-Amyloid Peptide in SH-SY5Y Cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Qinghua; HE Li; SUI Senfang

    2006-01-01

    Deposition of amyloid in the brain is a critical step in the pathogenesis of Alzheimer's disease. The endocytosis of β-amyloid peptide (Aβ) is an important factor among the many factors that contribute to the genesis of amyloid deposits. Since cholesterol participates in many important physiological processes, the present work investigated the relationship between the cellular cholesterol content and the endocytosis of the exogenic Aβ, and found that reduction of the cholesterol content by methyl-β-cyclodextrin could reduce the endocytosis of Aβ. The study indicates that the endocytosis of Aβ is partly mediated by cholesterol.

  7. Curcumin Supplementation Decreases Intestinal Adiposity Accumulation, Serum Cholesterol Alterations, and Oxidative Stress in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Maurilio da Silva Morrone

    2016-01-01

    Full Text Available The aim of this study was to investigate the potential of curcumin oral supplementation (50 and 100 mg/Kg/day, for 30 days in circumventing menopause-associated oxidative stress and lipid profile dysfunctions in a rat ovariectomy (OVX model. Female Wistar rats were operated and randomly divided into either sham-operated or OVX groups. Sham-operated group (n=8 and one OVX group (n=11 were treated with vehicle (refined olive oil, and the other two OVX groups received curcumin at 50 or 100 mg/Kg/day doses (n=8/group. OVX vehicle-treated animals presented a higher deposition of intestinal adipose tissue as well as increased serum levels of IL-6, LDL, and total cholesterol when compared to sham-operated rats. In addition, several oxidative stress markers in serum, blood, and liver (such as TBARS, carbonyl, reduced-sulphydryl, and nonenzymatic antioxidant defenses were altered toward a prooxidant status by OVX. Interestingly, curcumin supplementation attenuated most of these parameters to sham comparable values. Thus, the herein presented results show that curcumin may be useful to ameliorate lipid metabolism alterations and oxidative damage associated with hormone deprivation in menopause.

  8. Curcumin Supplementation Decreases Intestinal Adiposity Accumulation, Serum Cholesterol Alterations, and Oxidative Stress in Ovariectomized Rats.

    Science.gov (United States)

    Morrone, Maurilio da Silva; Schnorr, Carlos Eduardo; Behr, Guilherme Antônio; Gasparotto, Juciano; Bortolin, Rafael Calixto; da Boit Martinello, Katia; Saldanha Henkin, Bernardo; Rabello, Thallita Kelly; Zanotto-Filho, Alfeu; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2016-01-01

    The aim of this study was to investigate the potential of curcumin oral supplementation (50 and 100 mg/Kg/day, for 30 days) in circumventing menopause-associated oxidative stress and lipid profile dysfunctions in a rat ovariectomy (OVX) model. Female Wistar rats were operated and randomly divided into either sham-operated or OVX groups. Sham-operated group (n = 8) and one OVX group (n = 11) were treated with vehicle (refined olive oil), and the other two OVX groups received curcumin at 50 or 100 mg/Kg/day doses (n = 8/group). OVX vehicle-treated animals presented a higher deposition of intestinal adipose tissue as well as increased serum levels of IL-6, LDL, and total cholesterol when compared to sham-operated rats. In addition, several oxidative stress markers in serum, blood, and liver (such as TBARS, carbonyl, reduced-sulphydryl, and nonenzymatic antioxidant defenses) were altered toward a prooxidant status by OVX. Interestingly, curcumin supplementation attenuated most of these parameters to sham comparable values. Thus, the herein presented results show that curcumin may be useful to ameliorate lipid metabolism alterations and oxidative damage associated with hormone deprivation in menopause.

  9. Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishmania donovani Infected Macrophages: Implication in Therapy

    Science.gov (United States)

    Chakrabarti, Saikat; Roy, Syamal

    2016-01-01

    Background Previously we reported that Kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. Splenic macrophages (MΦ) of Leishmania donovani (LD) infected mice show decrease in membrane cholesterol, while LD infected macrophages (I-MΦ) show defective T cell stimulating ability that could be corrected by liposomal delivery of cholesterol. T helper cells recognize peptide antigen in the context of class II MHC molecule. It is known that the conformation of a large number of membrane proteins is dependent on membrane cholesterol. In this investigation we tried to understand the influence of decreased membrane cholesterol in I-MΦ on the conformation of MHC-II protein and peptide-MHC-II stability, and its bearing on the antigen specific T-cell activation. Methodology/Principal Findings MΦ of CBA/j mice were infected with Leishmania donovani (I-MΦ). Two different anti-Aκ mAbs were used to monitor the status of MHC-II protein under parasitized condition. One of them (11.5–2) was conformation specific, whereas the other one (10.2.16) was not. Under parasitized condition, the binding of 11.5–2 decreased significantly with respect to the normal counterpart, whereas that of 10.2.16 remained unaltered. The binding of 11.5–2 was restored to normal upon liposomal delivery of cholesterol in I-MΦ. By molecular dynamics (MD) simulation studies we found that there was considerable conformational fluctuation in the transmembrane domain of the MHC-II protein in the presence of membrane cholesterol than in its absence, which possibly influenced the distal peptide binding groove. This was evident from the faster dissociation of the cognate peptide from peptide-MHC complex under parasitized condition, which could be corrected by liposomal delivery of cholesterol in I-MΦ. Conclusion The decrease in membrane cholesterol in I-MΦ may lead to altered conformation of MHC II, and this may contribute to a faster dissociation of

  10. Alteration of daily and circadian rhythms following dopamine depletion in MPTP treated non-human primates.

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    Karim Fifel

    Full Text Available Disturbances of the daily sleep/wake cycle are common non-motor symptoms of Parkinson's disease (PD. However, the impact of dopamine (DA depletion on circadian rhythms in PD patients or non-human primate (NHP models of the disorder have not been investigated. We evaluated alterations of circadian rhythms in NHP following MPTP lesion of the dopaminergic nigro-striatal system. DA degeneration was assessed by in vivo PET ([(11C]-PE2I and post-mortem TH and DAT quantification. In a light∶dark cycle, control and MPTP-treated NHP both exhibit rest-wake locomotor rhythms, although DA-depleted NHP show reduced amplitude, decreased stability and increased fragmentation. In all animals, 6-sulphatoxymelatonin peaks at night and cortisol in early morning. When the circadian system is challenged by exposure to constant light, controls retain locomotor rest-wake and hormonal rhythms that free-run with stable phase relationships whereas in the DA-depleted NHP, locomotor rhythms are severely disturbed or completely abolished. The amplitude and phase relations of hormonal rhythms nevertheless remain unaltered. Use of a light-dark masking paradigm shows that expression of daily rest-wake activity in MPTP monkeys requires the stimulatory and inhibitory effects of light and darkness. These results suggest that following DA lesion, the central clock in the SCN remains intact but, in the absence of environmental timing cues, is unable to drive downstream rhythmic processes of striatal clock gene and dopaminergic functions that control locomotor output. These findings suggest that the circadian component of the sleep-wake disturbances in PD is more profoundly affected than previously assumed.

  11. Golgi enlargement in Arf-depleted yeast cells is due to altered dynamics of cisternal maturation

    Science.gov (United States)

    Bhave, Madhura; Papanikou, Effrosyni; Iyer, Prasanna; Pandya, Koushal; Jain, Bhawik Kumar; Ganguly, Abira; Sharma, Chandrakala; Pawar, Ketakee; Austin, Jotham; Day, Kasey J.; Rossanese, Olivia W.; Glick, Benjamin S.; Bhattacharyya, Dibyendu

    2014-01-01

    ABSTRACT Regulation of the size and abundance of membrane compartments is a fundamental cellular activity. In Saccharomyces cerevisiae, disruption of the ADP-ribosylation factor 1 (ARF1) gene yields larger and fewer Golgi cisternae by partially depleting the Arf GTPase. We observed a similar phenotype with a thermosensitive mutation in Nmt1, which myristoylates and activates Arf. Therefore, partial depletion of Arf is a convenient tool for dissecting mechanisms that regulate Golgi structure. We found that in arf1Δ cells, late Golgi structure is particularly abnormal, with the number of late Golgi cisternae being severely reduced. This effect can be explained by selective changes in cisternal maturation kinetics. The arf1Δ mutation causes early Golgi cisternae to mature more slowly and less frequently, but does not alter the maturation of late Golgi cisternae. These changes quantitatively explain why late Golgi cisternae are fewer in number and correspondingly larger. With a stacked Golgi, similar changes in maturation kinetics could be used by the cell to modulate the number of cisternae per stack. Thus, the rates of processes that transform a maturing compartment can determine compartmental size and copy number. PMID:24190882

  12. The behavioral effects of enriched housing are not altered by serotonin depletion but enrichment alters hippocampal neurochemistry.

    Science.gov (United States)

    Galani, Rodrigue; Berthel, Marie-Camille; Lazarus, Christine; Majchrzak, Monique; Barbelivien, Alexandra; Kelche, Christian; Cassel, Jean-Christophe

    2007-07-01

    To assess a possible role for serotonin in the mediation of the behavioral changes induced by enriched housing conditions (EC), adult female Long-Evans rats sustaining a serotonin depletion (150 microg of 5,7-dihydroxytryptamine, icv) and sham-operated rats were housed postoperatively for 30 days in enriched (12 rats/large cage containing various objects) or standard housing conditions (2 rats/standard laboratory cage). Thereafter, anxiety responses (elevated plus-maze), locomotor activity (in the home-cage), sensori-motor capabilities (beam-walking task), and spatial memory (eight-arm radial maze) were assessed. Monoamine levels were subsequently measured in the frontoparietal cortex and the hippocampus. Overall, EC reduced anxiety-related responses, enhanced sensori-motor performance and improved the memory span in the initial stage of the spatial memory task. Despite a substantial reduction of serotonergic markers in the hippocampus (82%) and the cortex (74%), these positive effects of EC were not altered by the lesion. EC reduced the serotonin levels in the ventral hippocampus (particularly in unlesioned rats: -23%), increased serotonin turnover in the entire hippocampus (particularly in lesioned rats: +36%) and augmented the norepinephrine levels in the dorsal hippocampus (+68% in unlesioned and +49% in lesioned rats); no such alterations were found in the frontoparietal cortex. Our data suggest that an intact serotonergic system is not a prerequisite for the induction of positive behavioral effects by EC. The neurochemical changes found in the hippocampus of EC rats, however, show that the monoaminergic innervation of the hippocampus is a target of EC. PMID:17493843

  13. Acute cholesterol depletion leads to net loss of the organic osmolyte taurine in Ehrlich Lettré tumor cells

    DEFF Research Database (Denmark)

    Villumsen, Kasper Rømer; Duelund, Lars; Lambert, Ian Henry

    2010-01-01

    In mammalian cells, the organic osmolyte taurine is accumulated by the Na-dependent taurine transporter TauT and released though the volume- and DIDS-sensitive organic anion channel. Incubating Ehrlich Lettré tumor cells with methyl-ß-cyclodextrin (5 mM, 1 h) reduces the total cholesterol pool to...

  14. Na+ Influx Induced by New Antimalarials Causes Rapid Alterations in the Cholesterol Content and Morphology of Plasmodium falciparum.

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    Sudipta Das

    2016-05-01

    Full Text Available Among the several new antimalarials discovered over the past decade are at least three clinical candidate drugs, each with a distinct chemical structure, that disrupt Na+ homeostasis resulting in a rapid increase in intracellular Na+ concentration ([Na+]i within the erythrocytic stages of Plasmodium falciparum. At present, events triggered by Na+ influx that result in parasite demise are not well-understood. Here we report effects of two such drugs, a pyrazoleamide and a spiroindolone, on intraerythrocytic P. falciparum. Within minutes following the exposure to these drugs, the trophozoite stage parasite, which normally contains little cholesterol, was made permeant by cholesterol-dependent detergents, suggesting it acquired a substantial amount of the lipid. Consistently, the merozoite surface protein 1 and 2 (MSP1 and MSP2, glycosylphosphotidylinositol (GPI-anchored proteins normally uniformly distributed in the parasite plasma membrane, coalesced into clusters. These alterations were not observed following drug treatment of P. falciparum parasites adapted to grow in a low [Na+] growth medium. Both cholesterol acquisition and MSP1 coalescence were reversible upon the removal of the drugs, implicating an active process of cholesterol exclusion from trophozoites that we hypothesize is inhibited by high [Na+]i. Electron microscopy of drug-treated trophozoites revealed substantial morphological changes normally seen at the later schizont stage including the appearance of partial inner membrane complexes, dense organelles that resemble "rhoptries" and apparent nuclear division. Together these results suggest that [Na+]i disruptor drugs by altering levels of cholesterol in the parasite, dysregulate trophozoite to schizont development and cause parasite demise.

  15. Cholesterol metabolism is altered in Rett syndrome: a study on plasma and primary cultured fibroblasts derived from patients.

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    Marco Segatto

    Full Text Available Rett (RTT syndrome is a severe neurological disorder that affects almost exclusively females. Several detectable mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2 are responsible for the onset of the disease. MeCP2 is a key transcription regulator involved in gene silencing via methylation-dependent remodeling of chromatin. Recent data highlight that lipid metabolism is perturbed in brains and livers of MECP2-null male mice. In addition, altered plasma lipid profile in RTT patients has been observed. Thus, the aim of the work is to investigate the protein network involved in cholesterol homeostasis maintenance on freshly isolated fibroblasts and plasma from both RTT and healthy donors. To this end, protein expression of 3-hydroxy-3methyl glutaryl Coenzyme A reductase (HMGR, sterol regulatory element binding proteins (SREBPs, low density lipoprotein receptor (LDLr and scavenger receptor B-1 (SRB-1 was assessed in cultured skin fibroblasts from unaffected individuals and RTT patients. In addition, lipid profile and the abundance of proprotein convertase subtilisin/kexin type 9 (PCSK9 were analyzed on plasma samples. The obtained results demonstrate that the main proteins belonging to cholesterol regulatory network are altered in RTT female patients, providing the proof of principle that cholesterol metabolism may be taken into account as a new target for the treatment of specific features of RTT pathology.

  16. Familial combined hyperlipidemia is associated with alterations in the cholesterol synthesis pathway

    Science.gov (United States)

    Familial combined hyperlipidemia (FCH) is a common familial lipid disorder characterized by increases in plasma total cholesterol, triglyceride, and apolipoprotein B-100 levels. In light of prior metabolic and genetic research, our purpose was to ascertain whether FCH cases had significant abnormali...

  17. Monocytes of patients with familial hypercholesterolemia show alterations in cholesterol metabolism

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    Soufi Muhidien

    2008-11-01

    Full Text Available Abstract Background Elevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze, if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH with those from healthy individuals. Methods Cholesterol and oxidized cholesterol metabolite serum levels of FH and of healthy, gender/age matched control subjects were measured by combined gas chromatography – mass spectroscopy. Monocytes from patients with FH and from healthy subjects were isolated by antibody-assisted density centrifugation. Gene expression profiles of isolated monocytes were measured using Affymetrix HG-U 133 Plus 2.0 microarrays. We compared monocyte gene expression profiles from FH patients with healthy controls using a Welch T-test with correction for multiple testing (p Results Using microarray analysis we found in FH patients a significant up-regulation of 1,617 genes and a down-regulation of 701 genes compared to monocytes from healthy individuals. These include genes of proteins that are involved in the uptake, biosynthesis, disposition, and cellular efflux of cholesterol. In addition, plasma from FH patients contains elevated amounts of sterols and oxysterols. An increased uptake of oxidized as well as of native LDL by FH monocytes combined with a down-regulation of NPC1 and ABCA1 explains the lipid accumulation observed in these cells. Conclusion Our data demonstrate that circulating FH monocytes show differences in cell physiology that may contribute to the early onset of atherosclerosis in this disease.

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

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    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.

  19. Cholesterol efflux pathways regulate myelopoiesis: A potential link to altered macrophage function in atherosclerosis

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    Andrew James Murphy

    2014-10-01

    Full Text Available Atherosclerotic cardiovascular disease (CVD is a chronic inflammatory disease of the blood vessels that can lead to myocardial infarction or stroke. The major cell in the atherosclerotic lesion, the macrophage is thought to be an important contributor to the production of inflammatory mediators that exacerbate this disease. Macrophages are generally derived from circulating monocytes, which are in turn produced by hematopoietic stem and multipotential progenitor cells (HSPCs in the bone marrow and other medullary organs. Recent studies suggest that disruption in cholesterol homeostasis or prolonged exposure to a hypercholesterolemic environment can influence HSPCs to over-produce monocytes, resulting in monocytosis. These monocytes may carry a pre-programed ability to become M1-like macrophages once they enter the atherosclerotic lesion. Future studies may help to differentiate the role of such pre-programming versus responses to local environmental cues in determining M1, M2 or other macrophage phenotypes in atherosclerotic lesions.

  20. Omega-3 Fatty Acid Enriched Chevon (Goat Meat Lowers Plasma Cholesterol Levels and Alters Gene Expressions in Rats

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    Mahdi Ebrahimi

    2014-01-01

    Full Text Available In this study, control chevon (goat meat and omega-3 fatty acid enriched chevon were obtained from goats fed a 50% oil palm frond diet and commercial goat concentrate for 100 days, respectively. Goats fed the 50% oil palm frond diet contained high amounts of α-linolenic acid (ALA in their meat compared to goats fed the control diet. The chevon was then used to prepare two types of pellets (control or enriched chevon that were then fed to twenty-male-four-month-old Sprague-Dawley rats (n=10 in each group for 12 weeks to evaluate their effects on plasma cholesterol levels, tissue fatty acids, and gene expression. There was a significant increase in ALA and docosahexaenoic acid (DHA in the muscle tissues and liver of the rats fed the enriched chevon compared with the control group. Plasma cholesterol also decreased (P<0.05 in rats fed the enriched chevon compared to the control group. The rat pellets containing enriched chevon significantly upregulated the key transcription factor PPAR-γ and downregulated SREBP-1c expression relative to the control group. The results showed that the omega-3 fatty acid enriched chevon increased the omega-3 fatty acids in the rat tissues and altered PPAR-γ and SREBP-1c genes expression.

  1. 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...

  2. ALTERATION OF CHOLESTEROL SULFATE IN HUMAN SERA DURING THE COURSE OF PREGNANCY

    Institute of Scientific and Technical Information of China (English)

    林蓓; 张淑兰; 岩森正男

    2004-01-01

    Objective To determine the concentrations of cholesterol sulfate (CS) in human sera and placental villi during the course of pregnancy. And to analyze its inhibitory activity on thrombin and further characterize the functional significance of CS. Methods The concentrations of CS were determined by thin-layer chromatography (TLC) on 60 cases of normal pregnant women and 30 cases of normal placental villi. The effect of CS in human sera on the activity of thrombin was analyzed. Results The concentrations of CS in human sera gradually increased from the first to third trimester of gestation with a correlation coefficient of 0.69, and a correlation between the concentration of CS and weeks of gestation (P <0.01 ). CS was also contained in the placental villi, and its concentrations at the second and third trimester of gestations were 4. 7 and 6. 2-fold of that at the first trimester of gestation. CS inhibited the activity of thrombin. Conclusion Placental CS is one of the sources of CS in the serum, probably by shedding. From the observation that CS inhibited the activity of thrombin, the increased expression of CS may play an important role in the regulation of blood coagulation during the course of pregnancy.

  3. Hyaluronan Accumulation Is Elevated in Cultures of Low Density Lipoprotein Receptor-deficient Cells and Is Altered by Manipulation of Cell Cholesterol Content*

    OpenAIRE

    Sakr, Sana W.; Potter-Perigo, Susan; Kinsella, Michael G.; Johnson, Pamela Y.; Braun, Kathleen R.; Goueffic, Yann; Rosenfeld, Michael E.; Wight, Thomas N.

    2008-01-01

    The extracellular matrix molecule hyaluronan (HA) accumulates in human atherosclerotic lesions. Yet the reasons for this accumulation have not been adequately addressed. Because abnormalities in lipid metabolism promote atherosclerosis, we have asked whether disrupted cholesterol homeostasis alters HA accumulation in low density lipoprotein receptor-deficient cell cultures. Cultured aortic smooth muscle cells (ASMC) from Watanabe heritable hyperlipidemic (WHHL) rabbits...

  4. Chlordecone, a mixed pregnane X receptor (PXR) and estrogen receptor alpha (ERα) agonist, alters cholesterol homeostasis and lipoprotein metabolism in C57BL/6 mice

    OpenAIRE

    Lee, Junga; Scheri, Richard C.; Zhang, Yuan; Curtis, Lawrence R.

    2008-01-01

    Chlordecone (CD) is one of many banned organochlorine (OC) insecticides that are widespread persistent organic pollutants. OC insecticides alter lipid homeostasis in rodents at doses that are not neurotoxic or carcinogenic. Pretreatment of mice or rats with CD altered tissue distribution of a subsequent dose of [14C]CD or [14C]cholesterol (CH). Nuclear receptors regulate expression of genes important in the homeostasis of CH and other lipids. In this study, we report that CD suppresses in vit...

  5. Behavioral expression of opiate withdrawal is altered after prefrontocortical dopamine depletion in rats: monoaminergic correlates.

    Science.gov (United States)

    Espejo, E F; Serrano, M I; Caillé, S; Stinus, L

    2001-08-01

    The objective of this study was to establish the effects of prefrontocortical dopamine depletion on opiate withdrawal and prefrontocortical neurochemical changes elicited by morphine dependence and withdrawal. The dopaminergic content was also measured in the nucleus accumbens during withdrawal, in order to detect reactive changes induced by prefrontocortical lesion. Withdrawal was induced by naloxone in morphine-dependent rats. Monoamine levels were analyzed post-mortem by high performance liquid cromatography. The results showed that chronic morphine dependence did not modify basal levels of monoamines in sham rats, revealing neuroadaptation of prefrontocortical dopamine, noradrenaline and serotonin systems to chronic morphine. The neuroadaptive phenomenon remained after prefrontocortical lesion (> 79% dopamine depletion). On the other hand, a strong increase of dopamine, noradrenaline, and serotonin contents in the medial prefrontal cortex of sham rats was detected during opiate withdrawal. However, in lesioned rats, the increase of prefrontocortical dopamine and serotonin content, but not that of noradrenaline, was much lower. In the nucleus accumbens, prefrontocortical lesion reactively enhanced the dopaminergic tone and, although opiate withdrawal reduced dopaminergic activity in both sham and lesioned rats, this reduction was less intense in the latter group. At a behavioral level, some symptoms of physical opiate withdrawal were exacerbated in lesioned rats (writhing, mastication, teeth-chattering, global score) and exploration was reduced. The findings hence indicate that: (i) prefrontocortical monoaminergic changes play a role in the behavioral expression of opiate withdrawal; (ii) the severity of some withdrawal signs are related to the dopaminergic and serotonergic tone of the medial prefrontal cortex rather than to the noradrenergic one, and (iii) an inverse relationship between mesocortical and mesolimbic dopaminergic systems exists. PMID:11425504

  6. Tissue Taurine Depletion Alters Metabolic Response to Exercise and Reduces Running Capacity in Mice

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    Takashi Ito

    2014-01-01

    Full Text Available Taurine is a sulfur-containing amino acid found in very high concentration in skeletal muscle. Taurine deficient mice engineered by knocking out the taurine transporter gene exhibit skeletal muscle wasting, structural defects, and exercise intolerance. In the present study, we investigated the mechanism underlying the development of metabolic abnormalities and exercise intolerance in muscle of the TauTKO phenotype. Running speed and endurance time of TauTKO mice were lower than those of control mice. Blood lactate level was elevated by >3-fold during treadmill running in TauTKO mice but remained largely unaltered by exercise in WT mice. Blood glucose was cleared faster during treadmill running in TauTKO mice than WT mice. AMP-activated kinase (AMPK β-2 subunit was reduced in TauTKO muscle concomitant with a reduction in α1 and α2 subunits of AMPK. The level of PPARα and its targets, Gpx3, Cpt2, and Echs1, were also decreased in TauTKO muscle. Collectively, taurine depletion impairs metabolic adaptation to exercise in skeletal muscle, a phenomenon associated with a downregulation of AMPK and diminished NADH utilization by the mitochondrial respiratory chain. These findings suggest a crucial role of taurine in regulating energy metabolism in skeletal muscle of exercising TauTKO mice, changes that contribute to impaired exercise endurance.

  7. Depletion of REF/Aly alters gene expression and reduces RNA polymerase II occupancy.

    Science.gov (United States)

    Stubbs, Sarah H; Conrad, Nicholas K

    2015-01-01

    Pre-mRNA processing is mechanistically linked to transcription with RNA pol II serving as a platform to recruit RNA processing factors to nascent transcripts. The TREX complex member, REF/Aly, has been suggested to play roles in transcription and nuclear RNA stability in addition to its more broadly characterized role in mRNA export. We employed RNA-seq to identify a subset of transcripts with decreased expression in both nuclear and cytoplasmic fractions upon REF/Aly knockdown, which implies that REF/Aly affects their expression upstream of its role in mRNA export. Transcription inhibition experiments and metabolic labeling assays argue that REF/Aly does not affect stability of selected candidate transcripts. Instead, ChIP assays and nuclear run-on analysis reveal that REF/Aly depletion diminishes the transcription of these candidate genes. Furthermore, we determined that REF/Aly binds directly to candidate transcripts, supporting a direct effect of REF/Aly on candidate gene transcription. Taken together, our data suggest that the importance of REF/Aly is not limited to RNA export, but that REF/Aly is also critical for gene expression at the level of transcription. Our data are consistent with the model that REF/Aly is involved in linking splicing with transcription efficiency.

  8. NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ Production

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    Eirini Christaki

    2015-01-01

    Full Text Available Background. Natural killer (NK and natural killer T (NKT cells contribute to the innate host defense but their role in bacterial sepsis remains controversial. Methods. C57BL/6 mice were infected intratracheally with 5 × 105 cfu of Streptococcus pneumoniae. Animals were divided into sham group (Sham; pretreated with isotype control antibody (CON group; pretreated with anti-asialo GM1 antibody (NKd group; and pretreated with anti-CD1d monoclonal antibody (NKTd group before bacterial challenge. Serum and tissue samples were analyzed for bacterial load, cytokine levels, splenocyte apoptosis rates, and cell characteristics by flow cytometry. Splenocyte miRNA expression was also analyzed and survival was assessed. Results. NK cell depletion prolonged survival. Upon inhibition of NKT cell activation, spleen NK (CD3−/NK1.1+ cells increased compared to all other groups. Inhibition of NKT cell activation led to higher bacterial loads and increased levels of serum and splenocyte IFN-γ. Splenocyte miRNA analysis showed that miR-200c and miR-29a were downregulated, while miR-125a-5p was upregulated, in anti-CD1d treated animals. These changes were moderate after NK cell depletion. Conclusions. NK cells appear to contribute to mortality in pneumococcal pneumonia. Inhibition of NKT cell activation resulted in an increase in spleen NK (CD3−/NK1.1+ cells and a higher IFN-γ production, while altering splenocyte miRNA expression.

  9. Involvement of gut microbial fermentation in the metabolic alterations occurring in n-3 polyunsaturated fatty acids-depleted mice

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    Carpentier Yvon A

    2011-06-01

    Full Text Available Abstract Backround Western diet is characterized by an insufficient n-3 polyunsaturated fatty acid (PUFA consumption which is known to promote the pathogenesis of several diseases. We have previously observed that mice fed with a diet poor in n-3 PUFA for two generations exhibit hepatic steatosis together with a decrease in body weight. The gut microbiota contributes to the regulation of host energy metabolism, due to symbiotic relationship with fermentable nutrients provided in the diet. In this study, we have tested the hypothesis that perturbations of the gut microbiota contribute to the metabolic alterations occurring in mice fed a diet poor in n-3 PUFA for two generations (n-3/- mice. Methods C57Bl/6J mice fed with a control or an n-3 PUFA depleted diet for two generations were supplemented with prebiotic (inulin-type Fructooligosaccharides, FOS, 0.20 g/day/mice during 24 days. Results n-3/-mice exhibited a marked drop in caecum weight, a decrease in lactobacilli and an increase in bifidobacteria in the caecal content as compared to control mice (n-3/+ mice. Dietary supplementation with FOS for 24 days was sufficient to increase caecal weight and bifidobacteria count in both n-3/+ and n-3/-mice. Moreover, FOS increased lactobacilli content in n-3/-mice, whereas it decreased their level in n-3/+ mice. Interestingly, FOS treatment promoted body weight gain in n-3/-mice by increasing energy efficiency. In addition, FOS treatment decreased fasting glycemia and lowered the higher expression of key factors involved in the fatty acid catabolism observed in the liver of n-3/-mice, without lessening steatosis. Conclusions the changes in the gut microbiota composition induced by FOS are different depending on the type of diet. We show that FOS may promote lactobacilli and counteract the catabolic status induced by n-3 PUFA depletion in mice, thereby contributing to restore efficient fat storage.

  10. What's Cholesterol?

    Science.gov (United States)

    ... 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- ...

  11. Exercise-Induced Changes in Caveolin-1, Depletion of Mitochondrial Cholesterol, and the Inhibition of Mitochondrial Swelling in Rat Skeletal Muscle but Not in the Liver

    Directory of Open Access Journals (Sweden)

    Damian Jozef Flis

    2016-01-01

    Full Text Available The reduction in cholesterol in mitochondria, observed after exercise, is related to the inhibition of mitochondrial swelling. Caveolin-1 (Cav-1 plays an essential role in the regulation of cellular cholesterol metabolism and is required by various signalling pathways. Therefore, the aim of this study was to investigate the effect of prolonged swimming on the mitochondrial Cav-1 concentration; additionally, we identified the results of these changes as they relate to the induction of changes in the mitochondrial swelling and cholesterol in rat skeletal muscle and liver. Male Wistar rats were divided into a sedentary control group and an exercise group. The exercised rats swam for 3 hours and were burdened with an additional 3% of their body weight. After the cessation of exercise, their quadriceps femoris muscles and livers were immediately removed for experimentation. The exercise protocol caused an increase in the Cav-1 concentration in crude muscle mitochondria; this was related to a reduction in the cholesterol level and an inhibition of mitochondrial swelling. There were no changes in rat livers, with the exception of increased markers of oxidative stress in mitochondria. These data indicate the possible role of Cav-1 in the adaptive change in the rat muscle mitochondria following exercise.

  12. Reduction of the cholesterol sensor SCAP in the brains of mice causes impaired synaptic transmission and altered cognitive function.

    Directory of Open Access Journals (Sweden)

    Ryo Suzuki

    Full Text Available The sterol sensor SCAP is a key regulator of SREBP-2, the major transcription factor controlling cholesterol synthesis. Recently, we showed that there is a global down-regulation of cholesterol synthetic genes, as well as SREBP-2, in the brains of diabetic mice, leading to a reduction of cholesterol synthesis. We now show that in mouse models of type 1 and type 2 diabetes, this is, in part, the result of a decrease of SCAP. Homozygous disruption of the Scap gene in the brains of mice causes perinatal lethality associated with microcephaly and gliosis. Mice with haploinsufficiency of Scap in the brain show a 60% reduction of SCAP protein and ~30% reduction in brain cholesterol synthesis, similar to what is observed in diabetic mice. This results in impaired synaptic transmission, as measured by decreased paired pulse facilitation and long-term potentiation, and is associated with behavioral and cognitive changes. Thus, reduction of SCAP and the consequent suppression of cholesterol synthesis in the brain may play an important role in the increased rates of cognitive decline and Alzheimer disease observed in diabetic states.

  13. Pancreatic β-Cell Dysfunction in Diet-Induced Obese Mice: Roles of AMP-Kinase, Protein Kinase Cε, Mitochondrial and Cholesterol Metabolism, and Alterations in Gene Expression.

    Directory of Open Access Journals (Sweden)

    Émilie Pepin

    Full Text Available Diet induced obese (DIO mice can be stratified according to their weight gain in response to high fat diet as low responders (LDR and high responders (HDR. This allows the study of β-cell failure and the transitions to prediabetes (LDR and early diabetes (HDR. C57BL/6N mice were fed for 8 weeks with a normal chow diet (ND or a high fat diet and stratified as LDR and HDR. Freshly isolated islets from ND, LDR and HDR mice were studied ex-vivo for mitochondrial metabolism, AMPK activity and signalling, the expression and activity of key enzymes of energy metabolism, cholesterol synthesis, and mRNA profiling. Severely compromised glucose-induced insulin secretion in HDR islets, as compared to ND and LDR islets, was associated with suppressed AMP-kinase activity. HDR islets also showed reduced acetyl-CoA carboxylase activity and enhanced activity of 3-hydroxy-3-methylglutaryl-CoA reductase, which led respectively to elevated fatty acid oxidation and increased cholesterol biosynthesis. HDR islets also displayed mitochondrial membrane hyperpolarization and reduced ATP turnover in the presence of elevated glucose. Expression of protein kinase Cε, which reduces both lipolysis and production of signals for insulin secretion, was elevated in DIO islets. Genes whose expression increased or decreased by more than 1.2-fold were minor between LDR and ND islets (17 differentially expressed, but were prominent between HDR and ND islets (1508 differentially expressed. In HDR islets, particularly affected genes were related to cell cycle and proliferation, AMPK signaling, mitochondrial metabolism and cholesterol metabolism. In conclusion, chronically reduced AMPK activity, mitochondrial dysfunction, elevated cholesterol biosynthesis in islets, and substantial alterations in gene expression accompany β-cell failure in HDR islets. The β-cell compensation process in the prediabetic state (LDR is largely independent of transcriptional adaptive changes, whereas the

  14. Alterations in cholesterol and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease.

    Science.gov (United States)

    Liu, Li; Zhang, Ke; Tan, Liang; Chen, Yu-Hua; Cao, Yun-Peng

    2015-01-01

    The aim of this study was to investigate the changes in the protein, cholesterol, and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease (AD), and identify potential blood biomarkers of the disease. A total of 31 Chinese patients with AD and 31 aged-matched control subjects were selected. Lipid rafts were isolated from platelets using Optiprep gradient centrifugation. The protein content of lipid rafts was evaluated using Micro BCA assay, the cholesterol content using molecular probes, ganglioside GM1 content using colorimetry and dot-blotting analysis. The results showed that the cholesterol and ganglioside GM1 content of lipid rafts from platelets was significantly higher in patients with AD than aged-matched control subjects, whereas the protein content of lipid rafts did not show any differences between the 2 groups. These results indicate that the increases in the cholesterol and ganglioside GM1 content of lipid rafts from the platelets of patients with AD might serve as a biochemical adjunct to the clinical diagnosis of AD.

  15. Altered GPM6A/M6 Dosage Impairs Cognition and Causes Phenotypes Responsive to Cholesterol in Human and Drosophila

    NARCIS (Netherlands)

    Gregor, A.; Kramer, J.M.; Voet, M. van der; Schanze, I.; Uebe, S.; Donders, R.; Reis, A.; Schenck, A.; Zweier, C.

    2014-01-01

    Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol-rich lipid rafts and promotes filopodia formation. We identified a de novo duplication of the GPM6A gene in a patient with learning disability and behavioral ano

  16. Selective depletion of Mac-1-expressing microglia in rat subventricular zone does not alter neurogenic response early after stroke.

    Science.gov (United States)

    Heldmann, Ursula; Mine, Yutaka; Kokaia, Zaal; Ekdahl, Christine T; Lindvall, Olle

    2011-06-01

    Ischemic stroke induces migration of newly formed neuroblasts, generated by neural stem cells in the adult rat subventricular zone (SVZ), towards the injured striatum where they differentiate into mature neurons. Stroke also leads to accumulation of microglia in the SVZ but their role for neurogenesis is unclear. Here we developed a method for selective depletion of the macrophage antigen complex-1 (Mac-1)-expressing microglia population in the SVZ by intraventricular injection of the immunotoxin Mac-1-saporin in rats. We found that the vast majority of Mac-1+ cells were Iba-1+ microglia. The Mac-1+ population was heterogeneous and included both a small proliferative pool of cells, which was not affected by middle cerebral artery occlusion (MCAO), and a larger subpopulation that changed morphologically into a semi-activated state in response to the insult. This subpopulation did not increase its expression of the phagocytic marker ED1 but exhibited high levels of triggering receptor expressed on myeloid cells-2 (TREM-2), associated with alternative microglia activation. A minor portion of the SVZ Mac-1+ cells originated from the blood early after stroke, but this macrophage population became much more substantial at later stages. Almost 80% reduction of Mac-1-expressing microglia, caused by Mac-1 saporin delivered just before and at 1 week after MCAO, did not alter the numbers of newly formed neuroblasts in the striatum or their migratory distance. These findings indicate that the Mac-1-expressing microglia in the SVZ do not play a major role either for the number of neuroblasts which exit the SVZ or their migration in the striatum early following stroke.

  17. Transcriptomic effects of depleted uranium on acetylcholine and cholesterol metabolisms in Alzheimer's disease model; Effets transcriptomiques de l'uranium appauvri sur les metabolismes de l'acetylcholine et du cholesterol chez un modele de maladie d'Alzheimer

    Energy Technology Data Exchange (ETDEWEB)

    Lestaevel, Ph.; Bensoussan, H.; Racine, R.; Airault, F.; Gourmelon, P.; Souidi, M. [Direction de la radioprotection de l' Homme, service de radiobiologie et d' epidemiologie, laboratoire de radiotoxicologie experimentale, institut de radioprotection et de surete nucleaire, BP no 17, 92262 Fontenay-aux-Roses cedex (France)

    2011-02-15

    Some heavy metals, or aluminium, could participate in the development of Alzheimer disease (AD). Depleted uranium (DU), another heavy metal, modulates the cholinergic system and the cholesterol metabolism in the brain of rats, but without neurological disorders. The aim of this study was to determine what happens in organisms exposed to DU that will/are developing the AD. This study was thus performed on a transgenic mouse model for human amyloid precursor protein (APP), the Tg2576 strain. The possible effects of DU through drinking water (20 mg/L) over an 8-month period were analyzed on acetylcholine and cholesterol metabolisms at gene level in the cerebral cortex. The mRNA levels of choline acetyl transferase (ChAT) vesicular acetylcholine transporter (VAChT) and ATP-binding cassette transporter A1 (ABC A1) decreased in control Tg2576 mice in comparison with wild-type mice (respectively -89%, -86% and -44%, p < 0.05). Chronic exposure of Tg2576 mice to DU increased mRNA levels of ChAT (+189%, p < 0.05), VAChT (+120%, p < 0.05) and ABC A1 (+52%, p < 0.05) compared to control Tg2576 mice. Overall, these modifications of acetylcholine and cholesterol metabolisms did not lead to increased disturbances that are specific of AD, suggesting that chronic DU exposure did not worsen the pathology in this experimental model. (authors)

  18. Grape Seed Procyanidins and Cholestyramine Differentially Alter Bile Acid and Cholesterol Homeostatic Gene Expression in Mouse Intestine and Liver.

    Directory of Open Access Journals (Sweden)

    Rebecca M Heidker

    Full Text Available Bile acid (BA sequestrants, lipid-lowering agents, may be prescribed as a monotherapy or combination therapy to reduce the risk of coronary artery disease. Over 33% of adults in the United States use complementary and alternative medicine strategies, and we recently reported that grape seed procyanidin extract (GSPE reduces enterohepatic BA recirculation as a means to reduce serum triglyceride (TG levels. The current study was therefore designed to assess the effects on BA, cholesterol and TG homeostatic gene expression following co-administration with GSPE and the BA sequestrant, cholestyramine (CHY. Eight-week old male C57BL/6 mice were treated for 4 weeks with either a control or 2% CHY-supplemented diet, after which, they were administered vehicle or GSPE for 14 hours. Liver and intestines were harvested and gene expression was analyzed. BA, cholesterol, non-esterified fatty acid and TG levels were also analyzed in serum and feces. Results reveal that GSPE treatment alone, and co-administration with CHY, regulates BA, cholesterol and TG metabolism differently than CHY administration alone. Notably, GSPE decreased intestinal apical sodium-dependent bile acid transporter (Asbt gene expression, while CHY significantly induced expression. Administration with GSPE or CHY robustly induced hepatic BA biosynthetic gene expression, especially cholesterol 7α-hydroxylase (Cyp7a1, compared to control, while co-administration further enhanced expression. Treatment with CHY induced both intestinal and hepatic cholesterologenic gene expression, while co-administration with GSPE attenuated the CHY-induced increase in the liver but not intestine. CHY also induced hepatic lipogenic gene expression, which was attenuated by co-administration with GSPE. Consequently, a 25% decrease in serum TG levels was observed in the CHY+GSPE group, compared to the CHY group. Collectively, this study presents novel evidence demonstrating that GSPE provides additive and

  19. Grape Seed Procyanidins and Cholestyramine Differentially Alter Bile Acid and Cholesterol Homeostatic Gene Expression in Mouse Intestine and Liver.

    Science.gov (United States)

    Heidker, Rebecca M; Caiozzi, Gianella C; Ricketts, Marie-Louise

    2016-01-01

    Bile acid (BA) sequestrants, lipid-lowering agents, may be prescribed as a monotherapy or combination therapy to reduce the risk of coronary artery disease. Over 33% of adults in the United States use complementary and alternative medicine strategies, and we recently reported that grape seed procyanidin extract (GSPE) reduces enterohepatic BA recirculation as a means to reduce serum triglyceride (TG) levels. The current study was therefore designed to assess the effects on BA, cholesterol and TG homeostatic gene expression following co-administration with GSPE and the BA sequestrant, cholestyramine (CHY). Eight-week old male C57BL/6 mice were treated for 4 weeks with either a control or 2% CHY-supplemented diet, after which, they were administered vehicle or GSPE for 14 hours. Liver and intestines were harvested and gene expression was analyzed. BA, cholesterol, non-esterified fatty acid and TG levels were also analyzed in serum and feces. Results reveal that GSPE treatment alone, and co-administration with CHY, regulates BA, cholesterol and TG metabolism differently than CHY administration alone. Notably, GSPE decreased intestinal apical sodium-dependent bile acid transporter (Asbt) gene expression, while CHY significantly induced expression. Administration with GSPE or CHY robustly induced hepatic BA biosynthetic gene expression, especially cholesterol 7α-hydroxylase (Cyp7a1), compared to control, while co-administration further enhanced expression. Treatment with CHY induced both intestinal and hepatic cholesterologenic gene expression, while co-administration with GSPE attenuated the CHY-induced increase in the liver but not intestine. CHY also induced hepatic lipogenic gene expression, which was attenuated by co-administration with GSPE. Consequently, a 25% decrease in serum TG levels was observed in the CHY+GSPE group, compared to the CHY group. Collectively, this study presents novel evidence demonstrating that GSPE provides additive and complementary

  20. About Cholesterol

    Science.gov (United States)

    ... 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 ...

  1. Alterations in high-density lipoprotein metabolism and reverse cholesterol transport in insulin resistance and type 2 diabetes mellitus : role of lipolytic enzymes, lecithin : cholesterol acyltransferase and lipid transfer proteins

    NARCIS (Netherlands)

    Borggreve, SE; de Vries, R; Dullaart, RPF

    2003-01-01

    Insulin resistance and type 2 diabetes mellitus are generally accompanied by low HDL cholesterol and high plasma triglycerides, which are major cardiovascular risk factors. This review describes abnormalities in HDL metabolism and reverse cholesterol transport, i.e. the transport of cholesterol from

  2. Chronic administration of cholesterol oximes in mice increases transcription of cytoprotective genes and improves transcriptome alterations induced by alpha-synuclein overexpression in nigrostriatal dopaminergic neurons.

    Science.gov (United States)

    Richter, Franziska; Gao, Fuying; Medvedeva, Vera; Lee, Patrick; Bove, Nicholas; Fleming, Sheila M; Michaud, Magali; Lemesre, Vincent; Patassini, Stefano; De La Rosa, Krystal; Mulligan, Caitlin K; Sioshansi, Pedrom C; Zhu, Chunni; Coppola, Giovanni; Bordet, Thierry; Pruss, Rebecca M; Chesselet, Marie-Françoise

    2014-09-01

    Cholesterol-oximes TRO19622 and TRO40303 target outer mitochondrial membrane proteins and have beneficial effects in preclinical models of neurodegenerative diseases leading to their advancement to clinical trials. Dopaminergic neurons degenerate in Parkinson's disease (PD) and are prone to oxidative stress and mitochondrial dysfunction. In order to provide insights into the neuroprotective potential of TRO19622 and TRO40303 for dopaminergic neurons in vivo, we assessed their effects on gene expression in laser captured nigrostriatal dopaminergic neurons of wildtype mice and of mice that over-express alpha-synuclein, a protein involved in both familial and sporadic forms of PD (Thy1-aSyn mice). Young mice were fed the drugs in food pellets or a control diet from 1 to 4months of age, approximately 10months before the appearance of striatal dopamine loss in this model. Unbiased weighted gene co-expression network analysis (WGCNA) of transcriptional changes revealed effects of cholesterol oximes on transcripts related to mitochondria, cytoprotection and anti-oxidant response in wild-type and transgenic mice, including increased transcription of stress defense (e.g. Prdx1, Prdx2, Glrx2, Hspa9, Pink1, Drp1, Trak1) and dopamine-related (Th, Ddc, Gch1, Dat, Vmat2, Drd2, Chnr6a) genes. Even at this young age transgenic mice showed alterations in transcripts implicated in mitochondrial function and oxidative stress (e.g. Bcl-2, Bax, Casp3, Nos2), and both drugs normalized about 20% of these alterations. Young Thy1-aSyn mice exhibit motor deficits that differ from parkinsonism and are established before the onset of treatment; these deficits were not improved by cholesterol oximes. However, high doses of TRO40303 improved olfaction and produced the same effects as dopamine agonists on a challenging beam test, specifically an increase in footslips, an observation congruent with its effects on transcripts involved in dopamine synthesis. High doses of TRO19622 increased alpha

  3. A single dose of rituximab does not deplete B cells in secondary lymphoid organs but alters phenotype and function

    NARCIS (Netherlands)

    Kamburova, E.G.; Koenen, H.J.P.M.; Borgman, K.J.; Berge, I.J. Ten; Joosten, I.; Hilbrands, L.B.

    2013-01-01

    A single dose of the anti-CD20 monoclonal antibody rituximab induces a nearly complete B cell depletion in peripheral blood, but not in secondary lymphoid organs. Modulation of this remaining B cell population due to rituximab treatment may contribute to the therapeutic effects of rituximab. To asse

  4. Altering the redox state of skeletal muscle by glutathione depletion increases the exercise‐activation of PGC‐1α

    OpenAIRE

    Strobel, Natalie A.; Matsumoto, Aya; Peake, Jonathan M.; Marsh, Susan A.; Peternelj, Tina‐Tinkara; Briskey, David; Fassett, Robert G.; Coombes, Jeff S.; Wadley, Glenn D.

    2014-01-01

    Abstract We investigated the relationship between markers of mitochondrial biogenesis, cell signaling, and antioxidant enzymes by depleting skeletal muscle glutathione with diethyl maleate (DEM) which resulted in a demonstrable increase in oxidative stress during exercise. Animals were divided into six groups: (1) sedentary control rats; (2) sedentary rats + DEM; (3) exercise control rats euthanized immediately after exercise; (4) exercise rats + DEM; (5) exercise control rats euthanized 4 h ...

  5. Chlordecone, a mixed pregnane X receptor (PXR) and estrogen receptor alpha (ERα) agonist, alters cholesterol homeostasis and lipoprotein metabolism in C57BL/6 mice

    International Nuclear Information System (INIS)

    Chlordecone (CD) is one of many banned organochlorine (OC) insecticides that are widespread persistent organic pollutants. OC insecticides alter lipid homeostasis in rodents at doses that are not neurotoxic or carcinogenic. Pretreatment of mice or rats with CD altered tissue distribution of a subsequent dose of [14C]CD or [14C]cholesterol (CH). Nuclear receptors regulate expression of genes important in the homeostasis of CH and other lipids. In this study, we report that CD suppresses in vitro reporter systems for human liver X receptors (LXRs) and activates those for human farnesoid X receptor (FXR), pregnane X receptor (PXR) and estrogen receptor α (ERα) in a concentration-dependent manner (0-50 μM). Consistent with human PXR activation in vitro, three days after a single dose of CD (15 mg/kg) hepatic microsomal CYP3A11 protein increases in C57BL/6 mice. CD decreases hepatic CH ester content without altering total CH concentration. Apolipoprotein A-I (apoA-I) contents of hepatic lipoprotein-rich and microsomal fractions of CD-treated mice are higher than controls. There is a significant reduction in non-high density lipoprotein CH but not apolipoprotein B-48/100 (apoB-48/100) in plasma from CD-treated mice after a 4 h fast. At 14 days after 15 mg CD/kg apoA-I and apoB-100 proteins but not CYP3A11 protein in hepatic microsomes are similar to controls. This work indicates that altered CH homeostasis is a mode of OC insecticide action of relevance after a single dose. This at least partially explains altered CH tissue distribution in CD-pretreated mice

  6. Chlordiazepoxide-induced released responding in extinction and punishment-conflict procedures is not altered by neonatal forebrain norepinephrine depletion.

    Science.gov (United States)

    Bialik, R J; Pappas, B A; Pusztay, W

    1982-02-01

    The effects of chlordiazepoxide (CDZ) in extinction and punishment-conflict tasks were examined in rats after neonatal systemic administration of 6-hydroxydopamine (6-OHDA) to deplete forebrain norepinephrine (NE). At about 70 days of age the rats were water deprived and trained for three days to drink in a novel apparatus. On the fourth day (test day) drinking was either extinguished by elimination of water from the drinking tube or punished by lick-contingent shock. Just prior to this test session half of the vehicle and half of the 6-OHDA treated rats were given an injection of CDZ (8 mg/kg IP). Both the injection of CDZ and forebrain NE depletion prolonged responding during extinction and reduced the suppressant effects of punishment in male rats, and these effects were of similar magnitude. Furthermore, CDZ was as effective in neonatal 6-OHDA treated male rats as in vehicle treated rats indicating that decreased transmission is ascending NE fibers caused by CDZ is not solely responsible for its behavioral effects in extinction and conflict tasks. Rather, these effects may involve cooperative mediation by both noradrenergic and serotonergic forebrain terminals. Unexpectedly, CDZ's anti-extinction effect was absent in female rats and its anti-conflict effect observed only in NE depleted females. PMID:7071081

  7. Systemic and Cardiac Depletion of M2 Macrophage through CSF-1R Signaling Inhibition Alters Cardiac Function Post Myocardial Infarction.

    Science.gov (United States)

    Leblond, Anne-Laure; Klinkert, Kerstin; Martin, Kenneth; Turner, Elizebeth C; Kumar, Arun H; Browne, Tara; Caplice, Noel M

    2015-01-01

    The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1 receptor signalling inhibition strategy to achieve their depletion. In mice, oral administration of GW2580, a CSF-1R kinase inhibitor, induced significant decreases in Gr1lo and F4/80hi monocyte populations in the circulation and the spleen. GW2580 administration also induced a significant depletion of M2 macrophages in the heart after 1 week treatment as well as a reduction of cardiac arginase1 and CD206 gene expression indicative of M2 macrophage activity. In a murine myocardial infarction model, reduced M2 macrophage content was associated with increased M1-related gene expression (IL-6 and IL-1β), and decreased M2-related gene expression (Arginase1 and CD206) in the heart of GW2580-treated animals versus vehicle-treated controls. M2 depletion was also associated with a loss in left ventricular contractile function, infarct enlargement, decreased collagen staining and increased inflammatory cell infiltration into the infarct zone, specifically neutrophils and M1 macrophages. Taken together, these data indicate that CSF-1R signalling is critical for maintaining cardiac tissue resident M2-polarized macrophage population, which is required for the resolution of inflammation post myocardial infarction and, in turn, for preservation of ventricular function.

  8. Microarray data on altered transcriptional program of Phgdh-deficient mouse embryonic fibroblasts caused by ʟ-serine depletion.

    Science.gov (United States)

    Hamano, Momoko; Sayano, Tomoko; Kusada, Wataru; Kato, Hisanori; Furuya, Shigeki

    2016-06-01

    Inherent ʟ-Ser deficiency culminates in intrauterine growth retardation, severe malformation of multiple organs particularly the central nervous system, and perinatal or early postnatal death in human and mouse. To uncover the molecular mechanisms underlying the growth-arrested phenotypes of l-Ser deficiency, we compared gene expression profiles of mouse embryonic fibroblasts deficient in 3-phosphoglycerate dehydrogenase (Phgdh), the first enzyme of de novo ʟ-Ser synthetic pathway, between ʟ-Ser-depleted and -supplemented conditions. The datasets (CEL and CHP files) from this study are publicly available on the Gene Expression Omnibus repository (accession number GEO: GSE55687). PMID:27222860

  9. Cholesterol (image)

    Science.gov (United States)

    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 ...

  10. 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...

  11. Altering the redox state of skeletal muscle by glutathione depletion increases the exercise-activation of PGC-1α.

    Science.gov (United States)

    Strobel, Natalie A; Matsumoto, Aya; Peake, Jonathan M; Marsh, Susan A; Peternelj, Tina-Tinkara; Briskey, David; Fassett, Robert G; Coombes, Jeff S; Wadley, Glenn D

    2014-12-01

    We investigated the relationship between markers of mitochondrial biogenesis, cell signaling, and antioxidant enzymes by depleting skeletal muscle glutathione with diethyl maleate (DEM) which resulted in a demonstrable increase in oxidative stress during exercise. Animals were divided into six groups: (1) sedentary control rats; (2) sedentary rats + DEM; (3) exercise control rats euthanized immediately after exercise; (4) exercise rats + DEM; (5) exercise control rats euthanized 4 h after exercise; and (6) exercise rats + DEM euthanized 4 h after exercise. Exercising animals ran on the treadmill at a 10% gradient at 20 m/min for the first 30 min. The speed was then increased every 10 min by 1.6 m/min until exhaustion. There was a reduction in total glutathione in the skeletal muscle of DEM treated animals compared to the control animals (P exercise (P Exercising animals given DEM showed a significantly greater increase in peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) mRNA compared to the control animals that were exercised (P exercise, PGC-1α gene expression was augmented. These findings further highlight the important role of exercise induced oxidative stress in the regulation of mitochondrial biogenesis. PMID:25538148

  12. Drebrin depletion alters neurotransmitter receptor levels in protein complexes, dendritic spine morphogenesis and memory-related synaptic plasticity in the mouse hippocampus.

    Science.gov (United States)

    Jung, Gangsoo; Kim, Eun-Jung; Cicvaric, Ana; Sase, Sunetra; Gröger, Marion; Höger, Harald; Sialana, Fernando Jayson; Berger, Johannes; Monje, Francisco J; Lubec, Gert

    2015-07-01

    Drebrin an actin-bundling key regulator of dendritic spine genesis and morphology, has been recently proposed as a regulator of hippocampal glutamatergic activity which is critical for memory formation and maintenance. Here, we examined the effects of genetic deletion of drebrin on dendritic spine and on the level of complexes containing major brain receptors. To this end, homozygous and heterozygous drebrin knockout mice generated in our laboratory and related wild-type control animals were studied. Level of protein complexes containing dopamine receptor D1/dopamine receptor D2, 5-hydroxytryptamine receptor 1A (5-HT1(A)R), and 5-hydroxytryptamine receptor 7 (5-HT7R) were significantly reduced in hippocampus of drebrin knockout mice whereas no significant changes were detected for GluR1, 2, and 3 and NR1 as examined by native gel-based immunoblotting. Drebrin depletion also altered dendritic spine formation, morphology, and reduced levels of dopamine receptor D1 in dendritic spines as evaluated using immunohistochemistry/confocal microscopy. Electrophysiological studies further showed significant reduction in memory-related hippocampal synaptic plasticity upon drebrin depletion. These findings provide unprecedented experimental support for a role of drebrin in the regulation of memory-related synaptic plasticity and neurotransmitter receptor signaling, offer relevant information regarding the interpretation of previous studies and help in the design of future studies on dendritic spines.

  13. Pantethine Alters Lipid Composition and Cholesterol Content of Membrane Rafts, With Down-Regulation of CXCL12-Induced T Cell Migration.

    Science.gov (United States)

    van Gijsel-Bonnello, Manuel; Acar, Niyazi; Molino, Yves; Bretillon, Lionel; Khrestchatisky, Michel; de Reggi, Max; Gharib, Bouchra

    2015-10-01

    Pantethine, a natural low-molecular-weight thiol, shows a broad activity in a large range of essential cellular pathways. It has been long known as a hypolipidemic and hypocholesterolemic agent. We have recently shown that it exerts a neuroprotective action in mouse models of cerebral malaria and Parkinson's disease through multiple mechanisms. In the present study, we looked at its effects on membrane lipid rafts that serve as platforms for molecules engaged in cell activity, therefore providing a target against inappropriate cell response leading to a chronic inflammation. We found that pantethine-treated cells showed a significant change in raft fatty acid composition and cholesterol content, with ultimate downregulation of cell adhesion, CXCL12-driven chemotaxis, and transendothelial migration of various T cell types, including human Jurkat cell line and circulating effector T cells. The mechanisms involved include the alteration of the following: (i) CXCL12 binding to its target cells; (ii) membrane dynamics of CXCR4 and CXCR7, the two CXCL12 receptors; and (iii) cell redox status, a crucial determinant in the regulation of the chemokine system. In addition, we considered the linker for activation of T cells molecule to show that pantethine effects were associated with the displacement from the rafts of the acylated signaling molecules which had their palmitoylation level reduced.. In conclusion, the results presented here, together with previously published findings, indicate that due to its pleiotropic action, pantethine can downregulate the multifaceted process leading to pathogenic T cell activation and migration.

  14. Pantethine Alters Lipid Composition and Cholesterol Content of Membrane Rafts, With Down-Regulation of CXCL12-Induced T Cell Migration.

    Science.gov (United States)

    van Gijsel-Bonnello, Manuel; Acar, Niyazi; Molino, Yves; Bretillon, Lionel; Khrestchatisky, Michel; de Reggi, Max; Gharib, Bouchra

    2015-10-01

    Pantethine, a natural low-molecular-weight thiol, shows a broad activity in a large range of essential cellular pathways. It has been long known as a hypolipidemic and hypocholesterolemic agent. We have recently shown that it exerts a neuroprotective action in mouse models of cerebral malaria and Parkinson's disease through multiple mechanisms. In the present study, we looked at its effects on membrane lipid rafts that serve as platforms for molecules engaged in cell activity, therefore providing a target against inappropriate cell response leading to a chronic inflammation. We found that pantethine-treated cells showed a significant change in raft fatty acid composition and cholesterol content, with ultimate downregulation of cell adhesion, CXCL12-driven chemotaxis, and transendothelial migration of various T cell types, including human Jurkat cell line and circulating effector T cells. The mechanisms involved include the alteration of the following: (i) CXCL12 binding to its target cells; (ii) membrane dynamics of CXCR4 and CXCR7, the two CXCL12 receptors; and (iii) cell redox status, a crucial determinant in the regulation of the chemokine system. In addition, we considered the linker for activation of T cells molecule to show that pantethine effects were associated with the displacement from the rafts of the acylated signaling molecules which had their palmitoylation level reduced.. In conclusion, the results presented here, together with previously published findings, indicate that due to its pleiotropic action, pantethine can downregulate the multifaceted process leading to pathogenic T cell activation and migration. PMID:25728249

  15. Good vs. Bad Cholesterol

    Science.gov (United States)

    ... 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 ...

  16. Altered expression of renal NHE3, TSC, BSC-1, and ENaC subunits in potassium-depleted rats.

    Science.gov (United States)

    Elkjaer, Marie-Louise; Kwon, Tae-Hwan; Wang, Weidong; Nielsen, Jakob; Knepper, Mark A; Frøkiaer, Jørgen; Nielsen, Søren

    2002-12-01

    The purpose of this study was to examine whether hypokalemia is associated with altered abundance of major renal Na+ transporters that may contribute to the development of urinary concentrating defects. We examined the changes in the abundance of the type 3 Na+/H+ exchanger (NHE3), Na+ - K+-ATPase, the bumetanide-sensitive Na+ - K+ - 2Cl- cotransporter (BSC-1), the thiazide-sensitive Na+ - Cl- cotransporter (TSC), and epithelial sodium channel (ENaC) subunits in kidneys of hypokalemic rats. Semiquantitative immunoblotting revealed that the abundance of BSC-1 (57%) and TSC (46%) were profoundly decreased in the inner stripe of the outer medulla (ISOM) and cortex/outer stripe of the outer medulla (OSOM), respectively. These findings were confirmed by immunohistochemistry. Moreover, total kidney abundance of all ENaC subunits was significantly reduced in response to the hypokalemia: alpha-subunit (61%), beta-subunit (41%), and gamma-subunit (60%), and this was confirmed by immunohistochemistry. In contrast, the renal abundance of NHE3 in hypokalemic rats was dramatically increased in cortex/OSOM (736%) and ISOM (210%). Downregulation of BSC-1, TSC, and ENaC may contribute to the urinary concentrating defect, whereas upregulation of NHE3 may be compensatory to prevent urinary Na+ loss and/or to maintain intracellular pH levels.

  17. Microbiota prevents cholesterol loss from the body by regulating host gene expression in mice.

    Science.gov (United States)

    Zhong, Chun-Yan; Sun, Wei-Wei; Ma, Yinyan; Zhu, Hongling; Yang, Pan; Wei, Hong; Zeng, Ben-Hua; Zhang, Qian; Liu, Yu; Li, Wen-Xia; Chen, Yixin; Yu, Liqing; Song, Zhi-Yuan

    2015-05-27

    We have previously observed that knockout of Niemann-Pick C1-Like 1 (NPC1L1), a cholesterol transporter essential for intestinal cholesterol absorption, reduces the output of dry stool in mice. As the food intake remains unaltered in NPC1L1-knockout (L1-KO) mice, we hypothesized that NPC1L1 deficiency may alter the gut microbiome to reduce stool output. Consistently, here we demonstrate that the phyla of fecal microbiota differ substantially between L1-KO mice and their wild-type controls. Germ-free (GF) mice have reduced stool output. Inhibition of NPC1L1 by its inhibitor ezetimibe reduces stool output in specific pathogen-free (SPF), but not GF mice. In addition, we show that GF versus SPF mice have reduced intestinal absorption and increased fecal excretion of cholesterol, particularly after treatment with ezetimibe. This negative balance of cholesterol in GF mice is associated with reduced plasma and hepatic cholesterol, and likely caused by reduced expression of NPC1L1 and increased expression of ABCG5 and ABCG8 in small intestine. Expression levels of other genes in intestine and liver largely reflect a state of cholesterol depletion and a decrease in intestinal sensing of bile acids. Altogether, our findings reveal a broad role of microbiota in regulating whole-body cholesterol homeostasis and its response to a cholesterol-lowering drug, ezetimibe.

  18. Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries

    Directory of Open Access Journals (Sweden)

    Meritxell Reverter

    2014-05-01

    Full Text Available Inhibition of cholesterol export from late endosomes causes cellular cholesterol imbalance, including cholesterol depletion in the trans-Golgi network (TGN. Here, using Chinese hamster ovary (CHO Niemann-Pick type C1 (NPC1 mutant cell lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6 accumulation into VAMP3, transferrin, and Rab11-positive recycling endosomes (REs. This increases Stx6/VAMP3 interaction and interferes with the recycling of αVβ3 and α5β1 integrins and cell migration, possibly in a Stx6-dependent manner. In NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN. Furthermore, elevation of RE cholesterol is associated with increased amounts of Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries together with a subset of cholesterol-sensitive SNARE proteins may play a regulatory role in cell migration and invasion.

  19. Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810

    Directory of Open Access Journals (Sweden)

    Mafu Akier

    2002-01-01

    Full Text Available Abstract Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent.

  20. Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition

    OpenAIRE

    Gelsomino, Giada; Corsetto, Paola A.; Campia, Ivana; Montorfano, Gigliola; Kopecka, Joanna; Castella, Barbara; Gazzano, Elena; Ghigo, Dario; Rizzo, Angela M; Riganti, Chiara

    2013-01-01

    Background The activity of P-glycoprotein (Pgp) and multidrug resistance related protein 1 (MRP1), two membrane transporters involved in multidrug resistance of colon cancer, is increased by high amounts of cholesterol in plasma membrane and detergent resistant membranes (DRMs). It has never been investigated whether omega 3 polyunsatured fatty acids (PUFAs), which modulate cholesterol homeostasis in dyslipidemic syndromes and have chemopreventive effects in colon cancer, may affect the respo...

  1. Effects of cholesterol on plasma membrane lipid order in MCF-7 cells by two-photon microscopy

    Science.gov (United States)

    Zeng, Yixiu; Chen, Jianling; Yang, Hongqin; Wang, Yuhua; Li, Hui; Xie, Shusen

    2014-09-01

    Lipid rafts are cholesterol- and glycosphingolipids- enriched microdomains on plasma membrane surface of mammal cells, involved in a variety of cellular processes. Depleting cholesterol from the plasma membrane by drugs influences the trafficking of lipid raft markers. Optical imaging techniques are powerful tools to study lipid rafts in live cells due to its noninvasive feature. In this study, breast cancer cells MCF-7 were treated with different concentrations of MβCD to deplete cholesterol and an environmentally sensitive fluorescence probe, Laurdan was loaded to image lipid order by two-photon microscopy. The generalized polarization (GP) values were calculated to distinguish the lipid order and disorder phase. GP images and GP distributions of native and cholesterol-depleted MCF-7 cells were obtained. Our results suggest that even at low concentration (0.5 mM) of MβCD, the morphology of the MCF-7 cells changes. Small high GP areas (lipid order phase) decrease more rapidly than low GP areas (lipid disorder phase), indicating that lipid raft structure was altered more severely than nonraft domains. The data demonstrates that cholesterol dramatically affect raft coverage and plasma membrane fluidity in living cells.

  2. Cholesterol Test

    Science.gov (United States)

    ... 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. Trans-generational study of DNA alterations and their consequences on life history traits and energy budget of Daphnia magna exposed to depleted uranium

    International Nuclear Information System (INIS)

    Understanding how toxicants affect species at various levels of biological organization is a major research goal in both ecotoxicology and radioecology. As part of IRSN program ENVIRHOM, which aims to assess environmental risks related to the presence of radionuclides in the environment, this PhD work explored how depleted uranium alters DNA and affects life history traits (survival, growth and reproduction) of an aquatic invertebrate, Daphnia magna. To answer to this problematic, an experimental approach and a modeling approach are conducted. An experimental study is performed to evaluate DNA accumulation and transmission during an uranium exposure (0; 2; 9.9; 22.2 and 50 μg.L-1) over two successive generations (F0 and F1). Different exposures scenarios (continuous, post-hatching and embryo exposure) are achieved to test the specific sensitivity of several life stages to uranium. Genotoxic effects are estimated using random amplified DNA technique combined with PCR (PCR-RAPD). In continuous and post-hatching exposure scenarios, results highlighted an accumulation and a transmission of DNA damage across generations with an increase in effect severity. DNA alterations are reported at hatching of the F1 generation at a concentration as low as 2 μg.L-1. Effects on growth and reproduction are stronger when the embryo stage is exposed and remain visible at 9.9 μg.L-1 despite a return in a clean medium at hatching. Results suggest that DNA damage could be used as early indicators of future effects on life history traits. A mechanistic analysis of experimental results is conducted using a DEBtox model (dynamic energy budget applied to toxicology) to better understand the causes of the increase in effect severity across generations. A model with two stress factors (one correlated to external concentration and another correlated to a damage level) is developed. Results of fits suggest the involvement of one second mode of action to explain immediate effects of uranium on

  4. Cholesterol and Your Child

    Science.gov (United States)

    ... 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 ...

  5. Women and Cholesterol

    Science.gov (United States)

    ... 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 ...

  6. HDL Cholesterol Test

    Science.gov (United States)

    ... 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 ; ...

  7. LDL Cholesterol Test

    Science.gov (United States)

    ... 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 ; ...

  8. Cholesterol IQ Quiz

    Science.gov (United States)

    ... 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 ...

  9. Chronic administration of cholesterol oximes in mice increases transcription of cytoprotective genes and improves transcriptome alterations induced by alpha-synuclein overexpression in nigrostriatal dopaminergic neurons

    OpenAIRE

    Richter, Franziska; Gao, Fuying; Medvedeva, Vera; Lee, Patrick; Bove, Nicholas; Fleming, Sheila M.; Michaud, Magali; Lemesre, Vincent; Patassini, Stefano; De La Rosa, Krystal; Mulligan, Caitlin K.; Sioshansi, Pedrom; Zhu, Chunni; COPPOLA, GIOVANNI; Bordet, Thierry

    2014-01-01

    Cholesterol-oximes TRO19622 and TRO40303 target outer mitochondrial membrane proteins and have beneficial effects in preclinical models of neurodegenerative diseases leading to their advancement to clinical trials. Dopaminergic neurons degenerate in Parkinson’s disease (PD) and are prone to oxidative stress and mitochondrial dysfunction. In order to provide insights into the neuroprotective potential of TRO19622 and TRO40303 for dopaminergic neurons in vivo, we assessed their effects on gene ...

  10. Exposure to depleted uranium does not alter the co-expression of HER-2/neu and p53 in breast cancer patients

    OpenAIRE

    Al-Toriahi Kaswer M; Jumaa Alaa S; Al-Janabi Asad A; Al-Mumen Mais M; Yasseen Akeel A

    2011-01-01

    Abstract Background Amongst the extensive literature on immunohistochemical profile of breast cancer, very little is found on populations exposed to a potential risk factor such as depleted uranium. This study looked at the immunohistochemical expression of HER-2/neu (c-erbB2) and p53 in different histological types of breast cancer found in the middle Euphrates region of Iraq, where the population has been exposed to high levels of depleted uranium. Findings The present investigation was per...

  11. The Structural Basis of Cholesterol Activity in Membranes

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-15

    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 modulates ER membrane behavior. Previous studies have predominantly examined cholesterol availability in terms of binding to extramembrane acceptors, but have provided limited insight into the structural changes underlying cholesterol activation. In this study, we use both molecular dynamics simulations and experimental membrane systems to examine the behavior of cholesterol in membrane bilayers. We find that cholesterol depth within the bilayer provides a reasonable structural metric for cholesterol availability and that this is correlated with cholesterol-acceptor binding. Further, the distribution of cholesterol availability in our simulations is continuous rather than divided into distinct available and unavailable pools. This data provide support for a revised cholesterol activation model in which activation is driven not by saturation of membrane-cholesterol interactions but rather by bulk membrane remodeling that reduces membrane-cholesterol affinity.

  12. 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...

  13. Beneficial effects of soy milk and fiber on high cholesterol diet-induced alteration of gut microbiota and inflammatory gene expression in rats.

    Science.gov (United States)

    Lee, Seung-Min; Han, Hye Won; Yim, Seung Yun

    2015-02-01

    We sought to evaluate whether a soy milk and fiber mixture could improve high cholesterol diet-induced changes in gut microbiota and inflammation. Sprague-Dawley rats were administered four different diets: CTRL (AIN76A diet), CHOL (AIN76A with 1% (w/w) cholesterol), SOY (CHOL diet, 20% of which was substituted with freeze-dried soy milk), or S.FIBER (SOY diet with 1.2% (w/w) psyllium, 6.2% (w/w) resistant maltodextrin, and 6.2% (w/w) chicory powder). A lipid profile and gene expression analysis demonstrated that SOY and S.FIBER improved the serum HDL-cholesterol and colonic expression levels of genes in tight junction (ZO-1 and occludin) and inflammation-related (IL-1β, IL-10, and Foxp3) proteins. S.FIBER lowered the serum MCP-1 concentration as well. A gut microbial analysis revealed that CHOL increased the ratio of Firmicutes to Bacteroidetes (F/B ratio). SOY increased the F/B ratio due to an increased proportion of Lactobacillus spp. S.FIBER greatly decreased the F/B ratio. Allobaculum spp. and Parabacteroides spp. exhibited a negative correlation with colonic expression of anti-inflammatory genes such as Foxp3, IL-10, occludin and ZO-1. CHOL increased the relative proportions of Allobaculum spp. and Parabacteroides spp. in the gut, while SOY and S.FIBER decreased these proportions. Diets containing soy milk and fiber mixtures could be beneficial by limiting CHOL-induced colonic inflammation and rescuing CHOL-disturbed gut microbiota. PMID:25477035

  14. The Toxicity of Depleted Uranium

    Directory of Open Access Journals (Sweden)

    Wayne Briner

    2010-01-01

    Full Text Available Depleted uranium (DU is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a clear and defined set of symptoms. Chronic low-dose, or subacute, exposure to depleted uranium alters the appearance of milestones in developing organisms. Adult animals that were exposed to depleted uranium during development display persistent alterations in behavior, even after cessation of depleted uranium exposure. Adult animals exposed to depleted uranium demonstrate altered behaviors and a variety of alterations to brain chemistry. Despite its reduced level of radioactivity evidence continues to accumulate that depleted uranium, if ingested, may pose a radiologic hazard. The current state of knowledge concerning DU is discussed.

  15. 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...

  16. 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- ...

  17. L-FABP T94A decreased fatty acid uptake and altered hepatic triglyceride and cholesterol accumulation in Chang liver cells stably transfected with L-FABP.

    Science.gov (United States)

    Gao, Na; Qu, Xia; Yan, Jin; Huang, Qi; Yuan, Hao-Yong; Ouyang, Dong-Sheng

    2010-12-01

    Liver fatty acid-binding protein (L-FABP, FABP1) is a highly conserved key factor in lipid metabolism. This study was undertaken to verify whether the T94A mutation in the L-FABP gene affects fatty acid uptake and intracellular esterification into specific lipid pools. Candidate SNPs were recreated using site-directed mutagenesis and tested for physical function in stably transfected Chang liver cell lines. We found that the T94A mutant of L-FABP lowered FFA uptake but had no effect on FFA efflux. L-FABP T94A-expressing cells showed decreased triglyceride content and increased cholesterol accumulation compared to the wild-type control for cells incubated with an FFA mixture (oleate: palmitate, 2:1 ratio). In conclusion, our study provided additional indications of the functional relevance of the L-FABP T94A SNP in hepatic fatty acid and lipid metabolism in humans.

  18. 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 ...

  19. 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 ...

  20. 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 ( ...

  1. Depleted uranium: Metabolic disruptor?

    International Nuclear Information System (INIS)

    The presence of uranium in the environment can lead to long-term contamination of the food chain and of water intended for human consumption and thus raises many questions about the scientific and societal consequences of this exposure on population health. Although the biological effects of chronic low-level exposure are poorly understood, results of various recent studies show that contamination by depleted uranium (DU) induces subtle but significant biological effects at the molecular level in organs including the brain, liver, kidneys and testicles. For the first time, it has been demonstrated that DU induces effects on several metabolic pathways, including those metabolizing vitamin D, cholesterol, steroid hormones, acetylcholine and xenobiotics. This evidence strongly suggests that DU might well interfere with many metabolic pathways. It might thus contribute, together with other man-made substances in the environment, to increased health risks in some regions. (authors)

  2. 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

  3. Exposure to depleted uranium does not alter the co-expression of HER-2/neu and p53 in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Al-Toriahi Kaswer M

    2011-03-01

    Full Text Available Abstract Background Amongst the extensive literature on immunohistochemical profile of breast cancer, very little is found on populations exposed to a potential risk factor such as depleted uranium. This study looked at the immunohistochemical expression of HER-2/neu (c-erbB2 and p53 in different histological types of breast cancer found in the middle Euphrates region of Iraq, where the population has been exposed to high levels of depleted uranium. Findings The present investigation was performed over a period starting from September 2008 to April 2009. Formalin-fixed, paraffin-embedded blocks from 70 patients with breast cancer (62 ductal and 8 lobular carcinoma were included in this study. A group of 25 patients with fibroadenoma was included as a comparative group, and 20 samples of normal breast tissue sections were used as controls. Labeled streptavidin-biotin (LSAB+ complex method was employed for immunohistochemical detection of HER-2/neu and p53. The detection rate of HER-2/neu and p53 immunohistochemical expression were 47.14% and 35.71% respectively in malignant tumors; expression was negative in the comparative and control groups (p HER-2/neu immunostaining was significantly associated with histological type, tumor size, nodal involvement, and recurrence of breast carcinoma (p p Both biomarkers were positively correlated with each other. Furthermore, all the cases that co-expressed both HER-2/neu and p53 showed the most unfavorable biopathological profile. Conclusion P53 and HER-2/neu over-expression play an important role in pathogenesis of breast carcinoma. The findings indicate that in regions exposed to high levels of depleted uranium, although p53 and HER-2/neu overexpression are both high, correlation of their expression with age, grade, tumor size, recurrence and lymph node involvement is similar to studies that have been conducted on populations not exposed to depleted uranium. HER-2/neu expression in breast cancer was higher

  4. 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

  5. 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

  6. 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.

  7. 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

  8. Naringenin ameliorates renal and platelet purinergic signalling alterations in high-cholesterol fed rats through the suppression of ROS and NF-κB signaling pathways.

    Science.gov (United States)

    Chtourou, Yassine; Kamoun, Zeineb; Zarrouk, Wissem; Kebieche, Mohammed; Kallel, Choumous; Gdoura, Radhouane; Fetoui, Hamadi

    2016-01-01

    Naringenin (NGEN) is a natural flavonoid aglycone of naringin that has been reported to have a wide range of pharmacological properties, such as antioxidant activity and free radical scavenging capacity. The aim of this study was to investigate the protective effect of NGEN on oxidative and inflammatory parameters, as well as to evaluate the hydrolysis of adenine nucleotides in kidney and platelet membranes of rats exposed to a hypercholesterolemic diet (HCD) for 90 days. Kidney oxidative stress and mRNA expression of the ectonucleoside triphosphate diphosphohydrolases (NTPDases), ecto-5'-nucleotidase (CD73), inducible NO synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and the nuclear factor kappa B (NF-κB) genes were evaluated by real time RT-PCR. The co-administration of NGEN (50 mg kg(-1)) for 90 days significantly prevented renal failure in HCD rats as indicated by an improvement of renal markers. Histopathological observation findings are also consistent with these effects. Moreover, NGEN (50 mg kg(-1)) significantly decreased the lipid profile and inhibited pro-oxidant and inflammation marker levels in the kidney of HCD rats. Furthermore, the NTPDase activities were significantly decreased in platelets and kidney membranes of HCD-treated rats and these alterations were improved by NGEN. In conclusion, this study suggests that naringenin can potentially improve the renal failure and platelet alterations observed in rats fed a hypercholesterolemic diet probably through its antioxidant effects. PMID:26565065

  9. 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.

  10. 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 ...

  11. 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, ...

  12. Effects of saturated and unsaturated fats given with and without dietary cholesterol on hepatic cholesterol synthesis and hepatic lipid metabolism.

    Science.gov (United States)

    Bochenek, W; Rodgers, J B

    1978-01-27

    Hepatic cholesterol synthesis was studied in rats after consuming diets of varying neutral lipid and cholesterol content. Cholesterol synthesis was evaluated by measuring 3-hydroxy-3-methylglutaryl-CoA reductase and by determining the rate of 3H-labeled sterol production from [3H]mevalonate. Results were correlated with sterol balance data and hepatic lipid content. Hepatic cholesterol synthesis was relatively great when cholesterol was excluded from the diet. The source of neutral dietary lipids, saturated vs. unsaturated, produced no change in hepatic sterol synthesis. Values for fecal sterol outputs and hepatic cholesterol levels were also similar in rats consuming either saturated or unsaturated fats. When 1% cholesterol was added to the diet, hepatic cholesterol synthesis was suppressed but the degree of suppression was greater in rats consuming unsaturated vs. saturated fats. This was associated with greater accumulation of cholesterol in livers from rats consuming unsaturates and a reduction in fecal neutral sterol output in this group as opposed to results from rats on saturated fats. Cholesterol consumption also altered the fatty acid composition of hepatic phospholipids producing decreases in the percentages of essential polyunsaturated fatty acids. It is concluded that dietary cholesterol alters cholesterol and fatty acid metabolism in the liver and that this effect is enhanced by dietary unsaturated fats.

  13. 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 ...

  14. Depletion of cellular iron by curcumin leads to alteration in histone acetylation and degradation of Sml1p in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Gajendra Kumar Azad

    Full Text Available Curcumin, a naturally occurring polyphenolic compound, is known to possess diverse pharmacological properties. There is a scarcity of literature documenting the exact mechanism by which curcumin modulates its biological effects. In the present study, we have used yeast as a model organism to dissect the mechanism underlying the action of curcumin. We found that the yeast mutants of histone proteins and chromatin modifying enzymes were sensitive to curcumin and further supplementation of iron resulted in reversal of the changes induced by curcumin. Additionally, treatment of curcumin caused the iron starvation induced expression of FET3, FRE1 genes. We also demonstrated that curcumin induces degradation of Sml1p, a ribonucleotide reductase inhibitor involved in regulating dNTPs production. The degradation of Sml1p was mediated through proteasome and vacuole dependent protein degradation pathways. Furthermore, curcumin exerts biological effect by altering global proteome profile without affecting chromatin architecture. These findings suggest that the medicinal properties of curcumin are largely contributed by its cumulative effect of iron starvation and epigenetic modifications.

  15. 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) ...

  16. 25-Hydroxycholesterol Increases the Availability of Cholesterol in Phospholipid Membranes

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, Brett N.; Schlesinger, Paul H.; Ory, Daniel S.; Baker, Nathan A.

    2011-02-01

    Side-chain oxysterols are enzymatically generated oxidation products of cholesterol that serve a central role in mediating cholesterol homeostasis. Recent work has shown that side-chain oxysterols, such as 25-hydroxycholesterol (25-HC), alter membrane structure in very different ways from cholesterol, suggesting a possible mechanism for how these oxysterols regulate cholesterol homeostasis. Here we extend our previous work, using molecular dynamics simulations of 25-HC and cholesterol mixtures in 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayers to examine interactions between 25-HC and cholesterol in the same bilayer. When added to cholesterol-containing membranes, 25-HC causes larger changes in membrane structure than when added to cholesterol-free membranes, demonstrating interactions between the two sterols. We also find that the presence of 25-HC changes the position, orientation, and solvent accessibility of cholesterol, shifting it into the water interface and therefore its availability to external acceptors. This is consistent with experimental results showing that oxysterols can trigger cholesterol trafficking from the plasma membrane to the endoplasmic reticulum. These interactions provide a potential mechanism for 25-HC-mediated regulation of cholesterol trafficking and homeostasis through direct modulation of cholesterol availability.

  17. Control of Angiogenesis by AIBP-mediated Cholesterol Efflux

    Science.gov (United States)

    Fang, Longhou; Choi, Soo-Ho; Baek, Ji Sun; Liu, Chao; Almazan, Felicidad; Ulrich, Florian; Wiesner, Philipp; Taleb, Adam; Deer, Elena; Pattison, Jennifer; Torres-Vázquez, Jesús; Li, Andrew C.; Miller, Yury I.

    2013-01-01

    Cholesterol is a structural component of the cell, indispensable for normal cellular function, but its excess often leads to abnormal proliferation, migration, inflammatory responses and/or cell death. To prevent cholesterol overload, ATP-binding cassette (ABC) transporters mediate cholesterol efflux from the cells to apolipoprotein A-I (ApoA-I) and to the ApoA-I-containing high-density lipoprotein (HDL)1-3. Maintaining efficient cholesterol efflux is essential for normal cellular function4-6. However, the role of cholesterol efflux in angiogenesis and the identity of its local regulators are poorly understood. Here we show that ApoA-I binding protein (AIBP) accelerates cholesterol efflux from endothelial cells (EC) to HDL and thereby regulates angiogenesis. AIBP/HDL-mediated cholesterol depletion reduces lipid rafts, interferes with VEGFR2 dimerization and signaling, and inhibits VEGF-induced angiogenesis in vitro and mouse aortic neovascularization ex vivo. Remarkably, Aibp regulates the membrane lipid order in embryonic zebrafish vasculature and functions as a non-cell autonomous regulator of zebrafish angiogenesis. Aibp knockdown results in dysregulated sprouting/branching angiogenesis, while forced Aibp expression inhibits angiogenesis. Dysregulated angiogenesis is phenocopied in Abca1/Abcg1-deficient embryos, and cholesterol levels are increased in Aibp-deficient and Abca1/Abcg1-deficient embryos. Our findings demonstrate that secreted AIBP positively regulates cholesterol efflux from EC and that effective cholesterol efflux is critical for proper angiogenesis. PMID:23719382

  18. 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

  19. Phytosterol ester constituents affect micellar cholesterol solubility in model bile.

    Science.gov (United States)

    Brown, Andrew W; Hang, Jiliang; Dussault, Patrick H; Carr, Timothy P

    2010-09-01

    Plant sterols and stanols (phytosterols) and their esters are nutraceuticals that lower LDL cholesterol, but the mechanisms of action are not fully understood. We hypothesized that intact esters and simulated hydrolysis products of esters (phytosterols and fatty acids in equal ratios) would differentially affect the solubility of cholesterol in model bile mixed micelles in vitro. Sodium salts of glycine- and taurine-conjugated bile acids were sonicated with phosphatidylcholine and either sterol esters or combinations of sterols and fatty acids to determine the amount of cholesterol solubilized into micelles. Intact sterol esters did not solubilize into micelles, nor did they alter cholesterol solubility. However, free sterols and fatty acids altered cholesterol solubility independently (no interaction effect). Equal contents of cholesterol and either campesterol, stigmasterol, sitosterol, or stigmastanol (sitostanol) decreased cholesterol solubility in micelles by approximately 50% compared to no phytosterol present, with stigmasterol performing slightly better than sitosterol. Phytosterols competed with cholesterol in a dose-dependent manner, demonstrating a 1:1 M substitution of phytosterol for cholesterol in micelle preparations. Unsaturated fatty acids increased the micelle solubility of sterols as compared with saturated or no fatty acids. No differences were detected in the size of the model micelles. Together, these data indicate that stigmasterol combined with saturated fatty acids may be more effective at lowering cholesterol micelle solubility in vivo.

  20. 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

  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. α-Tocopherol adipose tissue stores are depleted after burn injury in pediatric patients123

    Science.gov (United States)

    Leonard, Scott W; Traber, Daniel L; Traber, Lillian D; Gallagher, James; Bobe, Gerd; Jeschke, Marc G; Finnerty, Celeste C; Herndon, David

    2010-01-01

    Background: We previously showed that thermal injury depletes plasma vitamin E in pediatric burn patients; however, plasma changes may reflect immediate alterations in vitamin E nutriture. Adipose tissue α-tocopherol concentrations are generally accepted to reflect long-term vitamin E status. Objective: To test the hypothesis that thermal injury depletes body stores of vitamin E, α-tocopherol concentrations were measured in adipose tissue samples. Design: Pediatric patients (n = 8) were followed up to 1 y after burn injury. Surgically obtained samples were collected at various intervals and stored at −80°C in a biorepository. α- and γ-Tocopherols, cholesterol, and triglycerides were measured in the same tissue aliquot. Results: During the first week after injury, adipose tissue α-tocopherol concentrations were within the expected normal range of 199 ± 40 nmol/g adipose tissue but were substantially lower at weeks 2 and 3 (133 ± 13 and 109 ± 8 nmol/g adipose tissue, respectively). Individual rates of decrease, estimated by linear regression, showed that adipose tissue α-tocopherol decreased by an average of 6.1 ± 0.6 nmol/g daily. During the first month after injury, adipose tissue triglyceride concentrations also decreased, whereas no changes in cholesterol concentrations occurred. Conclusions: These data emphasize that the burn injury experienced by these pediatric patients altered their metabolism such that vitamin E status diminished during the month after injury. Further studies are needed to evaluate the mechanism and consequences of the observed vitamin E depletion. This trial was registered at clinicaltrials.gov as NCT00675714. PMID:20881067

  5. Alteration of aluminium inhibition of synaptosomal (Na(+)/K(+))ATPase by colestipol administration.

    Science.gov (United States)

    Silva, V S; Oliveira, L; Gonçalves, P P

    2013-11-01

    The ability of aluminium to inhibit the (Na(+)/K(+))ATPase activity has been observed by several authors. During chronic dietary exposure to AlCl3, brain (Na(+)/K(+))ATPase activity drops, even if no alterations of catalytic subunit protein expression and of energy charge potential are observed. The aluminium effect on (Na(+)/K(+))ATPase activity seems to implicate the reduction of interacting protomers within the oligomeric ensemble of the membrane-bound (Na(+)/K(+))ATPase. The activity of (Na(+)/K(+))ATPase is altered by the microviscosity of lipid environment. We studied if aluminium inhibitory effect on (Na(+)/K(+))ATPase is modified by alterations in synaptosomal membrane cholesterol content. Adult male Wistar rats were submitted to chronic dietary AlCl3 exposure (0.03 g/day of AlCl3) and/or to colestipol, a hypolidaemic drug (0.31 g/day) during 4 months. The activity of (Na(+)/K(+))ATPase was studied in brain cortex synaptosomes with different cholesterol contents. Additionally, we incubate synaptosomes with methyl-β-cyclodextrin for both enrichment and depletion of membrane cholesterol content, with or without 300 μM AlCl3. This enzyme activity was significantly reduced by micromolar AlCl3 added in vitro and when aluminium was orally administered to rats. The oral administration of colestipol reduced the cholesterol content and concomitantly inhibited the (Na(+)/K(+))ATPase. The aluminium inhibitory effect on synaptosomal (Na(+)/K(+))ATPase was reduced by cholesterol depletion both in vitro and in vivo.

  6. 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 ...

  7. DEPLETED URANIUM TECHNICAL WORK

    Science.gov (United States)

    The Depleted Uranium Technical Work is designed to convey available information and knowledge about depleted uranium to EPA Remedial Project Managers, On-Scene Coordinators, contractors, and other Agency managers involved with the remediation of sites contaminated with this mater...

  8. 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 ...

  9. 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...

  10. Cholesterol in unusual places

    Energy Technology Data Exchange (ETDEWEB)

    Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J, E-mail: John.Katsaras@nrc.gc.ca, E-mail: Norbert.Kucerka@nrc.gc.ca

    2010-11-01

    Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

  11. Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice.

    Science.gov (United States)

    Bura, Kanwardeep S; Lord, Caleb; Marshall, Stephanie; McDaniel, Allison; Thomas, Gwyn; Warrier, Manya; Zhang, Jun; Davis, Matthew A; Sawyer, Janet K; Shah, Ramesh; Wilson, Martha D; Dikkers, Arne; Tietge, Uwe J F; Collet, Xavier; Rudel, Lawrence L; Temel, Ryan E; Brown, J Mark

    2013-06-01

    Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the nonbiliary transintestinal cholesterol efflux (TICE) pathway. Scavenger receptor class B type I (SR-BI) plays a critical role in the classic hepatobiliary route of RCT. However, the role of SR-BI in TICE has not been studied. To examine the role of intestinal SR-BI in TICE, sterol balance was measured in control mice and mice transgenically overexpressing SR-BI in the proximal small intestine (SR-BI(hApoCIII-ApoAIV-Tg)). SR-BI(hApoCIII-ApoAIV-Tg) mice had significantly lower plasma cholesterol levels compared with wild-type controls, yet SR-BI(hApoCIII-ApoAIV-Tg) mice had normal fractional cholesterol absorption and fecal neutral sterol excretion. Both in the absence or presence of ezetimibe, intestinal SR-BI overexpression had no impact on the amount of cholesterol excreted in the feces. To specifically study effects of intestinal SR-BI on TICE we crossed SR-BI(hApoCIII-ApoAIV-Tg) mice into a mouse model that preferentially utilized the TICE pathway for RCT (Niemann-Pick C1-like 1 liver transgenic), and likewise found no alterations in cholesterol absorption or fecal sterol excretion. Finally, mice lacking SR-BI in all tissues also exhibited normal cholesterol absorption and fecal cholesterol disposal. Collectively, these results suggest that SR-BI is not rate limiting for intestinal cholesterol absorption or for fecal neutral sterol loss through the TICE pathway.

  12. Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation.

    Science.gov (United States)

    Evans, Malkanthi; Rumberger, John A; Azumano, Isao; Napolitano, Joseph J; Citrolo, Danielle; Kamiya, Toshikazu

    2014-01-01

    High serum concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease. The efficacy of pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD) risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP) guidelines. A total of 32 subjects were randomized to pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to 16) or placebo. Compared with placebo, the participants on pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040) and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively), and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively) that reached significance by week 16 (P=0.042). An 11% decrease in LDL-C from baseline was seen in participants on pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027) and 16 (P=0.010). The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants eligible for statins according to NCEP guidelines. PMID:24600231

  13. Raising HDL cholesterol in women

    Directory of Open Access Journals (Sweden)

    Danny J Eapen

    2009-11-01

    Full Text Available Danny J Eapen1, Girish L Kalra1, Luay Rifai1, Christina A Eapen2, Nadya Merchant1, Bobby V Khan11Emory University School of Medicine, Atlanta, GA, USA; 2University of South Florida School of Medicine, Tampa, FL, USAAbstract: High-density lipoprotein cholesterol (HDL-C concentration is essential in the determination of coronary heart disease (CHD risk in women. This is especially true in the postmenopausal state, where lipid profiles and CHD risk mimic that of age-matched men. Thus, interventions designed to reduce CHD risk by raising HDL-C levels may have particular significance during the transition to menopause. This review discusses HDL-C-raising therapies and the role of HDL in the primary prevention of CHD in women. Lifestyle-based interventions such as dietary change, aerobic exercise regimens, and smoking cessation are initial steps that are effective in raising HDL-C, and available data suggest women respond similarly to men with these interventions. When combined with pharmacotherapy, the effects of these lifestyle alterations are further amplified. Though studies demonstrating gender-specific differences in therapy are limited, niacin continues to be the most effective agent in raising HDL-C levels, especially when used in combination with fibrate or statin therapy. Emerging treatments such as HDL mimetic therapy show much promise in further raising HDL-C levels and improving cardiovascular outcomes.Keywords: high-density lipoprotein, HDL, women, cholesterol, heart disease

  14. Liver disease alters high-density lipoprotein composition, metabolism and function.

    Science.gov (United States)

    Trieb, Markus; Horvath, Angela; Birner-Gruenberger, Ruth; Spindelboeck, Walter; Stadlbauer, Vanessa; Taschler, Ulrike; Curcic, Sanja; Stauber, Rudolf E; Holzer, Michael; Pasterk, Lisa; Heinemann, Akos; Marsche, Gunther

    2016-07-01

    High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk.

  15. Liver disease alters high-density lipoprotein composition, metabolism and function.

    Science.gov (United States)

    Trieb, Markus; Horvath, Angela; Birner-Gruenberger, Ruth; Spindelboeck, Walter; Stadlbauer, Vanessa; Taschler, Ulrike; Curcic, Sanja; Stauber, Rudolf E; Holzer, Michael; Pasterk, Lisa; Heinemann, Akos; Marsche, Gunther

    2016-07-01

    High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk. PMID:27106140

  16. Aspirin inhibits formation of cholesterol rafts in fluid lipid membranes.

    Science.gov (United States)

    Alsop, Richard J; Toppozini, Laura; Marquardt, Drew; Kučerka, Norbert; Harroun, Thad A; Rheinstädter, Maikel C

    2015-03-01

    Aspirin and other non-steroidal anti-inflammatory drugs have a high affinity for phospholipid membranes, altering their structure and biophysical properties. Aspirin has been shown to partition into the lipid head groups, thereby increasing membrane fluidity. Cholesterol is another well known mediator of membrane fluidity, in turn increasing membrane stiffness. As well, cholesterol is believed to distribute unevenly within lipid membranes leading to the formation of lipid rafts or plaques. In many studies, aspirin has increased positive outcomes for patients with high cholesterol. We are interested if these effects may be, at least partially, the result of a non-specific interaction between aspirin and cholesterol in lipid membranes. We have studied the effect of aspirin on the organization of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) membranes containing cholesterol. Through Langmuir-Blodgett experiments we show that aspirin increases the area per lipid and decreases compressibility at 32.5 mol% cholesterol, leading to a significant increase of fluidity of the membranes. Differential scanning calorimetry provides evidence for the formation of meta-stable structures in the presence of aspirin. The molecular organization of lipids, cholesterol and aspirin was studied using neutron diffraction. While the formation of rafts has been reported in binary DPPC/cholesterol membranes, aspirin was found to locally disrupt membrane organization and lead to the frustration of raft formation. Our results suggest that aspirin is able to directly oppose the formation of cholesterol structures through non-specific interactions with lipid membranes.

  17. Depleted Uranium Management

    International Nuclear Information System (INIS)

    The paper considers radiological and toxic impact of the depleted uranium on the human health. Radiological influence of depleted uranium is less for 60 % than natural uranium due to the decreasing of short-lived isotopes uranium-234 and uranium-235 after enrichment. The formation of radioactive aerosols and their impact on the human are mentioned. Use of the depleted uranium weapons has also a chemical effect on intake due to possible carcinogenic influence on kidney. Uranium-236 in the substance of the depleted uranium is determined. The fact of beta-radiation formation in the uranium-238 decay is regarded. This effect practically is the same for both depleted and natural uranium. Importance of toxicity of depleted uranium, as the heavier chemical substance, has a considerable contribution to the population health. The paper analyzes risks regarding the use of the depleted uranium weapons. There is international opposition against using weapons with depleted uranium. Resolution on effects of the use of armaments and ammunitions containing depleted uranium was five times supported by the United Nations (USA, United Kingdom, France and Israel did not support). The decision for banning of depleted uranium weapons was supported by the European Parliament

  18. 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

  19. 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.

  20. Helicobacter pylori's cholesterol uptake impacts resistance to docosahexaenoic acid.

    Science.gov (United States)

    Correia, Marta; Casal, Susana; Vinagre, João; Seruca, Raquel; Figueiredo, Ceu; Touati, Eliette; Machado, José C

    2014-05-01

    Helicobacter pylori colonizes half of the world population and is associated with gastric cancer. We have previously demonstrated that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid known for its anti-inflammatory and antitumor effects, directly inhibits H. pylori growth in vitro and in mice. Nevertheless, the concentration of DHA shown to reduce H. pylori mice gastric colonization was ineffective in vitro. Related to the auxotrophy of H. pylori for cholesterol, we hypothesize that other mechanisms, in addition to DHA direct antibacterial effect, must be responsible for the reduction of the infection burden. In the present study we investigated if DHA affects also H. pylori growth, by reducing the availability of membrane cholesterol in the epithelial cell for H. pylori uptake. Levels of cholesterol in gastric epithelial cells and of cholesteryl glucosides in H. pylori were determined by thin layer chromatography and gas chromatography. The consequences of epithelial cells' cholesterol depletion on H. pylori growth were assessed in liquid cultures. We show that H. pylori uptakes cholesterol from epithelial cells. In addition, DHA lowers cholesterol levels in epithelial cells, decreases its de novo synthesis, leading to a lower synthesis of cholesteryl glucosides by H. pylori. A previous exposition of H. pylori to cholesterol influences the bacterium response to the direct inhibitory effect of DHA. Overall, our results suggest that a direct effect of DHA on H. pylori survival is modulated by its access to epithelial cell cholesterol, supporting the notion that cholesterol enhances the resistance of H. pylori. The cholesterol-dependent resistance of H. pylori to antimicrobial compounds raises new important aspects for the development of new anti-bacterial strategies. PMID:24447914

  1. 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

  2. Alpha-lipoic acid and N-acetylcysteine protects intensive swimming exercise-mediated germ-cell depletion, pro-oxidant generation, and alteration of steroidogenesis in rat testis.

    Science.gov (United States)

    Jana, Kuladip; Dutta, Ananya; Chakraborty, Pratip; Manna, Indranil; Firdaus, Syed Benazir; Bandyopadhyay, Debasish; Chattopadhyay, Ratna; Chakravarty, Baidyanath

    2014-09-01

    Prolonged and strenuous exercise has been proposed as a possible source of male-factor infertility. Forced intensive swimming has also been identified as one source of a dysfunctional male reproduction system. The present study evaluated the possible protective role of α-lipoic acid and N-acetylcysteine (NAC) on intensive swimming-induced germ-cell depletion in adult male rats. Forced exhaustive swimming of 1 hr/day, 6 days/week for 8 consecutive weeks resulted in a significant (P intensive forced swimming causes germ-cell depletion through the generation of ROS and depletion of steroidogenesis in the testis, which can be protected by the co-administration of α-lipoic acid and NAC. PMID:25104294

  3. Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation

    Directory of Open Access Journals (Sweden)

    Evans M

    2014-02-01

    Full Text Available Malkanthi Evans,1 John A Rumberger,2 Isao Azumano,3 Joseph J Napolitano,4 Danielle Citrolo,5 Toshikazu Kamiya5 1KGK Synergize Inc, London, ON, Canada; 2The Princeton Longevity Center, Princeton, NJ, USA; 3Daiichi Fine Chemical Co, Ltd, Toyama, Japan; 4Independent Consultant, Allentown, PA, USA; 5Kyowa Hakko USA, New York, NY, USA Abstract: High serum concentration of low-density lipoprotein cholesterol (LDL-C is a major risk factor for coronary heart disease. The efficacy of pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP guidelines. A total of 32 subjects were randomized to pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to16 or placebo. Compared with placebo, the participants on pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040 and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively, and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively that reached significance by week 16 (P=0.042. An 11% decrease in LDL-C from baseline was seen in participants on pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027 and 16 (P=0.010. The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants

  4. Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation

    OpenAIRE

    Evans M.; Rumberger JA; Azumano I; Napolitano JJ; Citrolo D; Kamiya T

    2014-01-01

    Malkanthi Evans,1 John A Rumberger,2 Isao Azumano,3 Joseph J Napolitano,4 Danielle Citrolo,5 Toshikazu Kamiya5 1KGK Synergize Inc, London, ON, Canada; 2The Princeton Longevity Center, Princeton, NJ, USA; 3Daiichi Fine Chemical Co, Ltd, Toyama, Japan; 4Independent Consultant, Allentown, PA, USA; 5Kyowa Hakko USA, New York, NY, USA Abstract: High serum concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease. The efficacy of pantethine trea...

  5. CHOLESTEROL AND CHOLESTEROL ESTER CONTENT OF BOVINE COLOSTRUM

    Science.gov (United States)

    Shope, Richard E.; Gowen, John W.

    1928-01-01

    The total amount of cholesterol found in colostrum and milk is comparatively low. The amount of cholesterol found in colostrum declines at an ever decreasing rate as milk secretion develops until at 48 hours the cholesterol is nearly the same as that found in milk 3 months or 7 months after parturition. The morning milk differs from the evening milk in that the cholesterol bound as ester is greater in amount. PMID:19869468

  6. Transintestinal cholesterol efflux

    NARCIS (Netherlands)

    van der Velde, Astrid E.; Brufau, Gemma; Groen, Albert K.

    2010-01-01

    Purpose of review Regulation of cholesterol homeostasis is a complex interplay of a multitude of metabolic pathways situated in different organs. The liver plays a central role and has received most attention of the research community. In this review, we discuss recent progress in the understanding

  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. Cholesterol transport in model membranes

    Science.gov (United States)

    Garg, Sumit; Porcar, Lionel; Butler, Paul; Perez-Salas, Ursula

    2010-03-01

    Physiological processes distribute cholesterol unevenly within the cell. The levels of cholesterol are maintained by intracellular transport and a disruption in the cell's ability to keep these normal levels will lead to disease. Exchange rates of cholesterol are generally studied in model systems using labeled lipid vesicles. Initially donor vesicles have all the cholesterol and acceptor vesicles are devoid of it. They are mixed and after some time the vesicles are separated and cholesterol is traced in each vesicle. The studies performed up to date have significant scatter indicating that the methodologies are not consistent. The present work shows in-situ Time-Resolved SANS studies of cholesterol exchange rates in unsaturated PC lipid vesicles. Molecular dynamics simulations were done to investigate the energetic and kinetic behavior of cholesterol in this system. This synergistic approach will provide insight into our efforts to understand cholesterol traffic.

  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. Depleted uranium in Japan

    International Nuclear Information System (INIS)

    In Japan, depleted uranium ammunition is regarded as nuclear weapons and meets with fierce opposition. The fact that US Marines mistakenly fired bullets containing depleted uranium on an island off Okinawa during training exercises in December 1995 and January 1996, also contributes. The overall situation in this area in Japan is outlined. (P.A.)

  11. Management of depleted uranium

    International Nuclear Information System (INIS)

    Large stocks of depleted uranium have arisen as a result of enrichment operations, especially in the United States and the Russian Federation. Countries with depleted uranium stocks are interested in assessing strategies for the use and management of depleted uranium. The choice of strategy depends on several factors, including government and business policy, alternative uses available, the economic value of the material, regulatory aspects and disposal options, and international market developments in the nuclear fuel cycle. This report presents the results of a depleted uranium study conducted by an expert group organised jointly by the OECD Nuclear Energy Agency and the International Atomic Energy Agency. It contains information on current inventories of depleted uranium, potential future arisings, long term management alternatives, peaceful use options and country programmes. In addition, it explores ideas for international collaboration and identifies key issues for governments and policy makers to consider. (authors)

  12. Water Depletion Threatens Agriculture

    Science.gov (United States)

    Brauman, K. A.; Richter, B. D.; Postel, S.; Floerke, M.; Malsy, M.

    2014-12-01

    Irrigated agriculture is the human activity that has by far the largest impact on water, constituting 85% of global water consumption and 67% of global water withdrawals. Much of this water use occurs in places where water depletion, the ratio of water consumption to water availability, exceeds 75% for at least one month of the year. Although only 17% of global watershed area experiences depletion at this level or more, nearly 30% of total cropland and 60% of irrigated cropland are found in these depleted watersheds. Staple crops are particularly at risk, with 75% of global irrigated wheat production and 65% of irrigated maize production found in watersheds that are at least seasonally depleted. Of importance to textile production, 75% of cotton production occurs in the same watersheds. For crop production in depleted watersheds, we find that one half to two-thirds of production occurs in watersheds that have not just seasonal but annual water shortages, suggesting that re-distributing water supply over the course of the year cannot be an effective solution to shortage. We explore the degree to which irrigated production in depleted watersheds reflects limitations in supply, a byproduct of the need for irrigation in perennially or seasonally dry landscapes, and identify heavy irrigation consumption that leads to watershed depletion in more humid climates. For watersheds that are not depleted, we evaluate the potential impact of an increase in irrigated production. Finally, we evaluate the benefits of irrigated agriculture in depleted and non-depleted watersheds, quantifying the fraction of irrigated production going to food production, animal feed, and biofuels.

  13. 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 ...

  14. Pantethine, a derivative of vitamin B(5) used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low- to moderate-cardiovascular risk North American subjects: a triple-blinded placebo and diet-controlled investigation.

    Science.gov (United States)

    Rumberger, John A; Napolitano, Joseph; Azumano, Isao; Kamiya, Toshikazu; Evans, Malkanthi

    2011-08-01

    Safety and efficacy of a biologically active derivative of vitamin B(5) (pantethine) on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) metabolism was studied in North American subjects at conventional low to moderate cardiovascular disease (CVD) risk. A total of 120 subjects initiated a therapeutic lifestyle change (TLC) diet 4 weeks before randomization (baseline) and maintained the diet throughout a 16-week study period; at baseline, subjects were randomized in a triple-blinded manner to either pantethine (600 mg/d, baseline to week 8, and 900 mg/d, weeks 9-16) or identically labeled, nonbiologically active placebo (n = 60 per group). We hypothesized that pantethine would lower TC and low-density lipoprotein in low-CVD-risk North American subjects in a similar manner as reported in high-CVD-risk subjects studied mainly in Italy and Japan. While sustaining a TLC diet and in comparison with placebo, pantethine demonstrated significant (P pantethine supplementation for 16 weeks (600 mg/d for weeks 1-8 then 900 mg/d for weeks 9-16) is safe and significantly lowers TC and LDL-C over and above the effect of TLC diet alone. Although the absolute magnitude of these effects was small in these low- to moderate-risk North Americans (4-6 mg/dL), the results are noteworthy as prior studies have shown that, for each 1 mg/dL (0.026 mmol/L) reduction in LDL-C, there is a concomitant 1% reduction in overall future CVD risk. PMID:21925346

  15. Uses of depleted uranium

    International Nuclear Information System (INIS)

    The depleted uranium is that in which percentage of uranium-235 fission executable is less than 0.2% or 0.3%. It is usually caused by the process of reprocessing the nuclear fuel burning, and also mixed with some other radioactive elements such as uranium 236, 238 and plutonium 239. The good features of the depleted uranium are its high density, low price and easily mined. So, the specifications for depleted uranium make it one of the best materials in case you need to have objects small in size, but quite heavy regarding its size. Uses of deplet ed uranium were relatively increased in domestic industrial uses as well as some uses in nuclear industry in the last few years. So it has increased uses in many areas of military and peaceful means such as: in balancing the giant air crafts, ships and missiles and in the manufacture of some types of concrete with severe hardness. (author)

  16. The modality effect of ego depletion: Auditory task modality reduces ego depletion.

    Science.gov (United States)

    Li, Qiong; Wang, Zhenhong

    2016-08-01

    An initial act of self-control that impairs subsequent acts of self-control is called ego depletion. The ego depletion phenomenon has been observed consistently. The modality effect refers to the effect of the presentation modality on the processing of stimuli. The modality effect was also robustly found in a large body of research. However, no study to date has examined the modality effects of ego depletion. This issue was addressed in the current study. In Experiment 1, after all participants completed a handgrip task, one group's participants completed a visual attention regulation task and the other group's participants completed an auditory attention regulation task, and then all participants again completed a handgrip task. The ego depletion phenomenon was observed in both the visual and the auditory attention regulation task. Moreover, participants who completed the visual task performed worse on the handgrip task than participants who completed the auditory task, which indicated that there was high ego depletion in the visual task condition. In Experiment 2, participants completed an initial task that either did or did not deplete self-control resources, and then they completed a second visual or auditory attention control task. The results indicated that depleted participants performed better on the auditory attention control task than the visual attention control task. These findings suggest that altering task modality may reduce ego depletion. PMID:27241617

  17. The modality effect of ego depletion: Auditory task modality reduces ego depletion.

    Science.gov (United States)

    Li, Qiong; Wang, Zhenhong

    2016-08-01

    An initial act of self-control that impairs subsequent acts of self-control is called ego depletion. The ego depletion phenomenon has been observed consistently. The modality effect refers to the effect of the presentation modality on the processing of stimuli. The modality effect was also robustly found in a large body of research. However, no study to date has examined the modality effects of ego depletion. This issue was addressed in the current study. In Experiment 1, after all participants completed a handgrip task, one group's participants completed a visual attention regulation task and the other group's participants completed an auditory attention regulation task, and then all participants again completed a handgrip task. The ego depletion phenomenon was observed in both the visual and the auditory attention regulation task. Moreover, participants who completed the visual task performed worse on the handgrip task than participants who completed the auditory task, which indicated that there was high ego depletion in the visual task condition. In Experiment 2, participants completed an initial task that either did or did not deplete self-control resources, and then they completed a second visual or auditory attention control task. The results indicated that depleted participants performed better on the auditory attention control task than the visual attention control task. These findings suggest that altering task modality may reduce ego depletion.

  18. Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats Clerodendron glandulosum Coleb., Verbenaceae, melhora a dieta rica em gordura induzida por alteração no metabolismo de lipídios e colesterol em ratos

    Directory of Open Access Journals (Sweden)

    RN Jadeja

    2010-03-01

    Full Text Available The present study was undertaken to evaluate the efficacy of freeze dried extract of Clerodendron glandulosum Coleb., Verbenaceae, leaves (FECG on alteration in lipid and cholesterol metabolism in high fat diet fed hyperlipidemic rats. Plasma and hepatic lipid profiles, lipid and cholesterol metabolizing enzymes in target tissues and fecal total lipids and bile acid contents were evaluated in FECG treated normolipidemic and hyperlipidemic rats. These results were compared with synthetic hypolipidemic drug Lovastatin (LVS. Results indicate that FECG was able to positively regulate induced experimental hyperlipidemia by significant alteration in plasma and tissue lipid profiles. These results can be attributed to reduced absorption, effective elimination and augmented catabolism of lipids and cholesterol possibly due to high content of saponin and phytosterols in C. glandulosum. Use of C. glandulosum extract as a potential therapeutic agent against hypercholesterolemia and hypertriglyceridemia is indicated.Este estudo foi realizado para avaliar a eficácia do extrato liofilizado das folhas de Clerodendron glandulosum Coleb., Verbenaceae (FECG, em alterar o metabolismo de lipídios e colesterol em ratos hiperlipidêmicos alimentados em uma dieta rica em gordura. Plasma e perfil lipídico hepático, lipídeos e enzimas que metabolizam o colesterol em tecidos-alvo e o conteúdo de lipídeos fecais totais e ácidos biliares foram avaliados em ratos normolipidêmicos e hiperlipidêmicos tratados com FECG. Os resultados foram comparados com a droga sintética hipolipemiante Lovastatina (LVS. Os resultados indicam que FECG foi capaz de regular positivamente a hiperlipidemia induzida experimentalmente por alteração significativa no perfil lipídico do plasma e tecidos. Estes resultados podem ser atribuídos à absorção reduzida, a eliminação efetiva e catabolismo aumentado de lipídeos e colesterol, possivelmente devido ao alto teor de saponina e

  19. Comparison of stereochemical structures of cholesterol from different sources by HPLC

    Directory of Open Access Journals (Sweden)

    Basri Satılmış

    2012-09-01

    Full Text Available It is known that only one stereoisomeric form, nat-cholesterol, naturally occurs. Nat-cholesterol and its enantiomer, ent-cholesterol, sometimes show enantiospecific interactions with biological molecules. If cholesterol is naturally found only one form, then the question of “why does cholesterol show an enantiomeric selectivity?” arises. For this purpose, stereoisomer analysis of cholesterol obtained from porcine liver and wool wax were carried out with three different high performance liquid chromatography (HPLC systems including reversed-phase, reversed-phase with different cyclodextrins as a mobile phase modifier, and chiral. Results from HPLC analysis of both cholesterol samples by permethylated γ-cyclodextrin and amylose tris-(3,5-dimethylphenylcarbamate chiral columns showed that there was no stereoisomer of cholesterol present. However reversed-phase HPLC analysis of cholesterol samples from porcine liver carried out with various cyclodextrins as mobile phase modifiers presented a peak which was not observed in the analysis of cholesterol samples from wool wax. On the other hand, different storage conditions of cholesterol samples and addition of cyclodextrins as mobile phase modifiers produced almost identical alterations in chromatograms of fresh samples by reversed-phase HPLC. This could be attributed to catalytic properties of cyclodextrins. Cyclodextrins may not be suitable as a mobile phase modifier in the stereoisomer analysis of cholesterol with high performance liquid chromatography.

  20. 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

  1. Intrinsic Depletion or Not

    DEFF Research Database (Denmark)

    Klösgen, Beate; Bruun, Sara; Hansen, Søren;

    with an AFM (2).    The intuitive explanation for the depletion based on "hydrophobic mismatch" between the obviously hydrophilic bulk phase of water next to the hydrophobic polymer. It would thus be an intrinsic property of all interfaces between non-matching materials. The detailed physical interaction path......  The presence of a depletion layer of water along extended hydrophobic interfaces, and a possibly related formation of nanobubbles, is an ongoing discussion. The phenomenon was initially reported when we, years ago, chose thick films (~300-400Å) of polystyrene as cushions between a crystalline...

  2. Intrinsic Depletion or Not

    DEFF Research Database (Denmark)

    Klösgen, Beate; Bruun, Sara; Hansen, Søren;

    with an AFM (2). The intuitive explanation for the depletion based on "hydrophobic mismatch" between the obviously hydrophilic bulk phase of water next to the hydrophobic polymer. It would thus be an intrinsic property of all interfaces between non-matching materials. The detailed physical interaction path......  The presence of a depletion layer of water along extended hydrophobic interfaces, and a possibly related formation of nanobubbles, is an ongoing discussion. The phenomenon was initially reported when we, years ago, chose thick films (~300-400Å) of polystyrene as cushions between a crystalline...

  3. Shear-affected depletion interaction

    NARCIS (Netherlands)

    July, C.; Kleshchanok, D.; Lang, P.R.

    2012-01-01

    We investigate the influence of flow fields on the strength of the depletion interaction caused by disc-shaped depletants. At low mass concentration of discs, it is possible to continuously decrease the depth of the depletion potential by increasing the applied shear rate until the depletion force i

  4. Food combinations for cholesterol lowering.

    Science.gov (United States)

    Harland, Janice I

    2012-12-01

    Reducing elevated LDL-cholesterol is a key public health challenge. There is substantial evidence from randomised controlled trials (RCT) that a number of foods and food components can significantly reduce LDL-cholesterol. Data from RCT have been reviewed to determine whether effects are additive when two or more of these components are consumed together. Typically components, such as plant stanols and sterols, soya protein, β-glucans and tree nuts, when consumed individually at their target rate, reduce LDL-cholesterol by 3-9 %. Improved dietary fat quality, achieved by replacing SFA with unsaturated fat, reduces LDL-cholesterol and can increase HDL-cholesterol, further improving blood lipid profile. It appears that the effect of combining these interventions is largely additive; however, compliance with multiple changes may reduce over time. Food combinations used in ten 'portfolio diet' studies have been reviewed. In clinical efficacy studies of about 1 month where all foods were provided, LDL-cholesterol is reduced by 22-30 %, whereas in community-based studies of >6 months' duration, where dietary advice is the basis of the intervention, reduction in LDL-cholesterol is about 15 %. Inclusion of MUFA into 'portfolio diets' increases HDL-cholesterol, in addition to LDL-cholesterol effects. Compliance with some of these dietary changes can be achieved more easily compared with others. By careful food component selection, appropriate to the individual, the effect of including only two components in the diet with good compliance could be a sustainable 10 % reduction in LDL-cholesterol; this is sufficient to make a substantial impact on cholesterol management and reduce the need for pharmaceutical intervention.

  5. Cholesterol enhances surface water diffusion of phospholipid bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Chi-Yuan; Kausik, Ravinath; Han, Songi, E-mail: songi@chem.ucsb.edu [Department of Chemistry and Biochemistry and Materials Research Laboratory, University of California, Santa Barbara, California 93106 (United States); Olijve, Luuk L. C. [Laboratory of Macromolecular and Organic Chemistry and Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB, Eindhoven (Netherlands)

    2014-12-14

    Elucidating the physical effect of cholesterol (Chol) on biological membranes is necessary towards rationalizing their structural and functional role in cell membranes. One of the debated questions is the role of hydration water in Chol-embedding lipid membranes, for which only little direct experimental data are available. Here, we study the hydration dynamics in a series of Chol-rich and depleted bilayer systems using an approach termed {sup 1}H Overhauser dynamic nuclear polarization (ODNP) NMR relaxometry that enables the sensitive and selective determination of water diffusion within 5–10 Å of a nitroxide-based spin label, positioned off the surface of the polar headgroups or within the nonpolar core of lipid membranes. The Chol-rich membrane systems were prepared from mixtures of Chol, dipalmitoyl phosphatidylcholine and/or dioctadecyl phosphatidylcholine lipid that are known to form liquid-ordered, raft-like, domains. Our data reveal that the translational diffusion of local water on the surface and within the hydrocarbon volume of the bilayer is significantly altered, but in opposite directions: accelerated on the membrane surface and dramatically slowed in the bilayer interior with increasing Chol content. Electron paramagnetic resonance (EPR) lineshape analysis shows looser packing of lipid headgroups and concurrently tighter packing in the bilayer core with increasing Chol content, with the effects peaking at lipid compositions reported to form lipid rafts. The complementary capability of ODNP and EPR to site-specifically probe the hydration dynamics and lipid ordering in lipid membrane systems extends the current understanding of how Chol may regulate biological processes. One possible role of Chol is the facilitation of interactions between biological constituents and the lipid membrane through the weakening or disruption of strong hydrogen-bond networks of the surface hydration layers that otherwise exert stronger repulsive forces, as reflected in

  6. Cholesterol enhances surface water diffusion of phospholipid bilayers

    Science.gov (United States)

    Cheng, Chi-Yuan; Olijve, Luuk L. C.; Kausik, Ravinath; Han, Songi

    2014-12-01

    Elucidating the physical effect of cholesterol (Chol) on biological membranes is necessary towards rationalizing their structural and functional role in cell membranes. One of the debated questions is the role of hydration water in Chol-embedding lipid membranes, for which only little direct experimental data are available. Here, we study the hydration dynamics in a series of Chol-rich and depleted bilayer systems using an approach termed 1H Overhauser dynamic nuclear polarization (ODNP) NMR relaxometry that enables the sensitive and selective determination of water diffusion within 5-10 Å of a nitroxide-based spin label, positioned off the surface of the polar headgroups or within the nonpolar core of lipid membranes. The Chol-rich membrane systems were prepared from mixtures of Chol, dipalmitoyl phosphatidylcholine and/or dioctadecyl phosphatidylcholine lipid that are known to form liquid-ordered, raft-like, domains. Our data reveal that the translational diffusion of local water on the surface and within the hydrocarbon volume of the bilayer is significantly altered, but in opposite directions: accelerated on the membrane surface and dramatically slowed in the bilayer interior with increasing Chol content. Electron paramagnetic resonance (EPR) lineshape analysis shows looser packing of lipid headgroups and concurrently tighter packing in the bilayer core with increasing Chol content, with the effects peaking at lipid compositions reported to form lipid rafts. The complementary capability of ODNP and EPR to site-specifically probe the hydration dynamics and lipid ordering in lipid membrane systems extends the current understanding of how Chol may regulate biological processes. One possible role of Chol is the facilitation of interactions between biological constituents and the lipid membrane through the weakening or disruption of strong hydrogen-bond networks of the surface hydration layers that otherwise exert stronger repulsive forces, as reflected in faster

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. 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 – ...

  13. 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 ...

  14. 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 ...

  15. A case of abdominal pain with dyslipidemia: difficulties diagnosing cholesterol ester storage disease.

    Science.gov (United States)

    Cameron, S J; Daimee, U; Block, R C

    2015-01-01

    Cholesterol ester storage disease is an exceptionally rare dyslipidemia with less than 150 cases reported in the medical literature. The diagnosis of Cholesterol Ester Storage Disease is often missed by virtue of the fact that the symptoms mimic both inborn metabolic defects and hepatic steatosis. Patients with Cholesterol Ester Storage Disease usually present with atypical complaints including abdominal pain from altered gut motility. Blood analysis typically reveals abnormal liver function tests with coincident dyslipidemia. We present a case of a young woman with Cholesterol Ester Storage Disease who was followed over two decades. We discuss issues common to her initial protracted diagnosis with management options over time.

  16. Depletion of intense fields

    CERN Document Server

    Seipt, D; Marklund, M; Bulanov, S S

    2016-01-01

    The interaction of charged particles and photons with intense electromagnetic fields gives rise to multi-photon Compton and Breit-Wheeler processes. These are usually described in the framework of the external field approximation, where the electromagnetic field is assumed to have infinite energy. However, the multi-photon nature of these processes implies the absorption of a significant number of photons, which scales as the external field amplitude cubed. As a result, the interaction of a highly charged electron bunch with an intense laser pulse can lead to significant depletion of the laser pulse energy, thus rendering the external field approximation invalid. We provide relevant estimates for this depletion and find it to become important in the interaction between fields of amplitude $a_0 \\sim 10^3$ and electron bunches with charges of the order of nC.

  17. Capital expenditure and depletion

    Energy Technology Data Exchange (ETDEWEB)

    Rech, O.; Saniere, A

    2003-07-01

    In the future, the increase in oil demand will be covered for the most part by non conventional oils, but conventional sources will continue to represent a preponderant share of the world oil supply. Their depletion represents a complex challenge involving technological, economic and political factors. At the same time, there is reason for concern about the decrease in exploration budgets at the major oil companies. (author)

  18. Capital expenditure and depletion

    International Nuclear Information System (INIS)

    In the future, the increase in oil demand will be covered for the most part by non conventional oils, but conventional sources will continue to represent a preponderant share of the world oil supply. Their depletion represents a complex challenge involving technological, economic and political factors. At the same time, there is reason for concern about the decrease in exploration budgets at the major oil companies. (author)

  19. Loss of liver FA binding protein significantly alters hepatocyte plasma membrane microdomains[S

    OpenAIRE

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

    2012-01-01

    Although lipid-rich microdomains of hepatocyte plasma membranes serve as the major scaffolding regions for cholesterol transport proteins important in cholesterol disposition, little is known regarding intracellular factors regulating cholesterol distribution therein. On the basis of its ability to bind cholesterol and alter hepatic cholesterol accumulation, the cytosolic liver type FA binding protein (L-FABP) was hypothesized to be a candidate protein regulating these microdomains. Compared ...

  20. Characterization of placental cholesterol transport

    DEFF Research Database (Denmark)

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

    2008-01-01

    circulation might attenuate congenital malformations. The cholesterol transporters Abca1, Abcg1, and Sr-b1 are present in placenta; however, their potential role in placental transport remains undetermined. In mice, expression analyses showed that Abca1 and Abcg1 transcripts increased 2-3-fold between...... 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...

  1. Ozone-depleting Substances (ODS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — This site includes all of the ozone-depleting substances (ODS) recognized by the Montreal Protocol. The data include ozone depletion potentials (ODP), global...

  2. 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)

  3. Cholesterol testing on a smartphone.

    Science.gov (United States)

    Oncescu, Vlad; Mancuso, Matthew; Erickson, David

    2014-02-21

    Home self-diagnostic tools for blood cholesterol monitoring have been around for over a decade but their widespread adoption has been limited by the relatively high cost of acquiring a quantitative test-strip reader, complicated procedure for operating the device, and inability to easily store and process results. To address this we have developed a smartphone accessory and software application that allows for the quantification of cholesterol levels in blood. Through a series of human trials we demonstrate that the system can accurately quantify total cholesterol levels in blood within 60 s by imaging standard test strips. In addition, we demonstrate how our accessory is optimized to improve measurement sensitivity and reproducibility across different individual smartphones. With the widespread adoption of smartphones and increasingly sophisticated image processing technology, accessories such as the one presented here will allow cholesterol monitoring to become more accurate and widespread, greatly improving preventive care for cardiovascular disease.

  4. 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

  5. Formation of cholesterol bilayer domains precedes formation of cholesterol crystals in cholesterol/dimyristoylphosphatidylcholine membranes: EPR and DSC studies.

    Science.gov (United States)

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

    2013-08-01

    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 analogues, it was shown that the CBDs begin to form at ~50 mol % cholesterol. It was confirmed by DSC that the cholesterol solubility threshold for DMPC membranes is detected at ~66 mol % cholesterol. At levels above this cholesterol content, monohydrate cholesterol crystals start to form. The major finding is that the formation of CBDs precedes formation of cholesterol crystals. The region of the phase diagram for cholesterol contents between 50 and 66 mol % is described as a structured one-phase region in which CBDs have to be supported by the surrounding DMPC bilayer saturated with cholesterol. Thus, the phase boundary located at 66 mol % cholesterol separates the structured one-phase region (liquid-ordered phase of DMPC with CBDs) from the two-phase region where the structured liquid-ordered phase of DMPC coexists with cholesterol crystals. It is likely that CBDs are precursors of monohydrate cholesterol crystals.

  6. Niemann Pick type C cells show cholesterol dependent decrease of APP expression at the cell surface its increased processing through the ?-secretase pathway

    OpenAIRE

    Malnar, Martina; KOŠIČEK, MARKO; Mitterreiter, Stefan; Omerbašić, Damir; Lichtenthaler, Stefan F.; Goate, Alison; Hećimović, Silva

    2010-01-01

    Abstract The link between cholesterol and Alzheimer's disease has recently been revealed in Niemann Pick type C disease. We found that NPC1-/- cells show decreased expression of APP at the cell surface and increased processing of APP through the ?-secretase pathway resulting in increased C99, sAPP? and intracellular A?40 levels. This effect is dependent on increased cholesterol levels, since cholesterol depletion reversed cell surface APP expression and lowered A?/C99 levels in NPC...

  7. 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.

  8. 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 ...

  9. Cholesterol-mediated surfactant dysfunction is mitigated by surfactant protein A.

    Science.gov (United States)

    Hiansen, Joshua Qua; Keating, Eleonora; Aspros, Alex; Yao, Li-Juan; Bosma, Karen J; Yamashita, Cory M; Lewis, James F; Veldhuizen, Ruud A W

    2015-03-01

    The ability of pulmonary surfactant to reduce surface tension at the alveolar surface is impaired in various lung diseases. Recent animal studies indicate that elevated levels of cholesterol within surfactant may contribute to its inhibition. It was hypothesized that elevated cholesterol levels within surfactant inhibit human surfactant biophysical function and that these effects can be reversed by surfactant protein A (SP-A). The initial experiment examined the function of surfactant from mechanically ventilated trauma patients in the presence and absence of a cholesterol sequestering agent, methyl-β-cyclodextrin. The results demonstrated improved surface activity when cholesterol was sequestered in vitro using a captive bubble surfactometer (CBS). These results were explored further by reconstitution of surfactant with various concentrations of cholesterol with and without SP-A, and testing of the functionality of these samples in vitro with the CBS and in vivo using surfactant depleted rats. Overall, the results consistently demonstrated that surfactant function was inhibited by levels of cholesterol of 10% (w/w phospholipid) but this inhibition was mitigated by the presence of SP-A. It is concluded that cholesterol-induced surfactant inhibition can actively contribute to physiological impairment of the lungs in mechanically ventilated patients and that SP-A levels may be important to maintain surfactant function in the presence of high cholesterol within surfactant. PMID:25522687

  10. Imaging approaches for analysis of cholesterol distribution and dynamics in the plasma membrane.

    Science.gov (United States)

    Wüstner, Daniel; Modzel, Maciej; Lund, Frederik W; Lomholt, Michael A

    2016-09-01

    Cholesterol is an important lipid component of the plasma membrane (PM) of mammalian cells, where it is involved in control of many physiological processes, such as endocytosis, cell migration, cell signalling and surface ruffling. In an attempt to explain these functions of cholesterol, several models have been put forward about cholesterol's lateral and transbilayer organization in the PM. In this article, we review imaging techniques developed over the last two decades for assessing the distribution and dynamics of cholesterol in the PM of mammalian cells. Particular focus is on fluorescence techniques to study the lateral and inter-leaflet distribution of suitable cholesterol analogues in the PM of living cells. We describe also several methods for determining lateral cholesterol dynamics in the PM including fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS), single particle tracking (SPT) and spot variation FCS coupled to stimulated emission depletion (STED) microscopy. For proper interpretation of such measurements, we provide some background in probe photophysics and diffusion phenomena occurring in cell membranes. In particular, we show the equivalence of the reaction-diffusion approach, as used in FRAP and FCS, and continuous time random walk (CTRW) models, as often invoked in SPT studies. We also discuss mass spectrometry (MS) based imaging of cholesterol in the PM of fixed cells and compare this method with fluorescence imaging of sterols. We conclude that evidence from many experimental techniques converges towards a model of a homogeneous distribution of cholesterol with largely free and unhindered diffusion in both leaflets of the PM. PMID:27016337

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

    Science.gov (United States)

    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

    2009-05-01

    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 several cholesterol-depleted species resembling small alpha, prebeta-1, and other prebeta forms. Selective delipidation markedly increases efficacy of plasma to stimulate ABCA1-mediated cholesterol transfer from monocytic cells to HDL. Plasma from African Green monkeys underwent selective HDL delipidation. The delipidated plasma was reinfused into five monkeys. Prebeta-1-like HDL had a plasma residence time of 8 +/- 6 h and was converted entirely to large alpha-HDL having residence times of 13-14 h. Small alpha-HDL was converted entirely to large alpha-HDL. These findings suggest that selective HDL delipidation activates reverse cholesterol transport, in vivo and in vitro. Treatment with delipidated plasma tended to reduce diet-induced aortic atherosclerosis in monkeys measured by intravascular ultrasound. These findings link the conversion of small to large HDL, in vivo, to improvement in atherosclerosis. PMID:19144994

  12. The membrane as the gatekeeper of infection: Cholesterol in host-pathogen interaction.

    Science.gov (United States)

    Kumar, G Aditya; Jafurulla, Md; Chattopadhyay, Amitabha

    2016-09-01

    The cellular plasma membrane serves as a portal for the entry of intracellular pathogens. An essential step for an intracellular pathogen to gain entry into a host cell therefore is to be able to cross the cell membrane. In this review, we highlight the role of host membrane cholesterol in regulating the entry of intracellular pathogens using insights obtained from work on the interaction of Leishmania and Mycobacterium with host cells. The entry of these pathogens is known to be dependent on host membrane cholesterol. Importantly, pathogen entry is inhibited either upon depletion (or complexation), or enrichment of membrane cholesterol. In other words, an optimum level of host membrane cholesterol is necessary for efficient infection by pathogens. In this overall context, we propose a general mechanism, based on cholesterol-induced conformational changes, involving cholesterol binding sites in host cell surface receptors that are implicated in this process. A therapeutic strategy targeting modulation of membrane cholesterol would have the advantage of avoiding the commonly encountered problem of drug resistance in tackling infection by intracellular pathogens. Insights into the role of host membrane cholesterol in pathogen entry would be instrumental in the development of novel therapeutic strategies to effectively tackle intracellular pathogenesis. PMID:26902688

  13. Stratospheric ozone depletion

    International Nuclear Information System (INIS)

    The amount of stratospheric ozone and the reduction of the ozone layer vary according to seasons and latitudes. At present total and vertical ozone is monitored over all Austria. The mean monthly ozone levels between 1994 and 2000 are presented. Data on stratospheric ozone and UV-B radiation are published daily on the home page http: www.lebesministerium.at. The use of ozone depleting substances such as chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs) is provided. Besides, the national measures taken to reduce their use. Figs. 2, Tables 2. (nevyjel)

  14. 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...

  15. Facts about...Blood Cholesterol. Revised.

    Science.gov (United States)

    National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.

    This fact sheet on blood cholesterol examines the connection between cholesterol and heart disease, lists risk factors for heart disease that can and cannot be controlled, points out who can benefit from lowering blood cholesterol, distinguishes between blood and dietary cholesterol, describes low density lipoprotein and high density lipoprotein…

  16. 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

  17. Cholesterol-rich lipid rafts play an important role in the Cyprinid herpesvirus 3 replication cycle.

    Science.gov (United States)

    Brogden, Graham; Adamek, Mikołaj; Proepsting, Marcus J; Ulrich, Reiner; Naim, Hassan Y; Steinhagen, Dieter

    2015-09-30

    The Cyprinus herpesvirus 3 (CyHV-3) is a member of the new Alloherpesviridae virus family in the Herpesvirales order. CyHV-3 has been implicated in a large number of disease outbreaks in carp populations causing up to 100% mortality. The aim of this study was to investigate the requirement of cholesterol-rich lipid rafts in CyHV-3 entry and replication in carp cells. Plasma membrane cholesterol was depleted from common carp brain (CCB) cells with methyl-β-cyclodextrin (MβCD). Treated and non-treated cells were infected with CyHV-3 and virus binding and infection parameters were assessed using RT-qPCR, immunocytochemistry and virus titration. The effect of cholesterol reduction severely stunted virus entry in vitro, however after cholesterol replenishment virus entry and subsequent replication rates were similar to the control infection. Furthermore, cholesterol depletion did not significantly influence virus binding and the subsequent post-entry replication stage, however had an impact on virus egress. Comparative analysis of the lipid compositions of CyHV-3 and CCB membrane fractions revealed strong similarities between the lipid composition of the CyHV-3 and CCB lipid rafts. The results presented here show that cholesterol-rich lipid rafts are important for the CyHV-3 replication cycle especially during entry and egress.

  18. 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

  19. Up-regulation of cholesterol associated genes as novel resistance mechanism in glioblastoma cells in response to archazolid B

    Energy Technology Data Exchange (ETDEWEB)

    Hamm, Rebecca; Zeino, Maen [Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany); Frewert, Simon [Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research and Department of Pharmaceutical Biotechnology, Saarland University, Saarbrücken (Germany); Efferth, Thomas, E-mail: efferth@uni-mainz.de [Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany)

    2014-11-15

    Treatment of glioblastoma multiforme (GBM), the most common and aggressive lethal brain tumor, represents a great challenge. Despite decades of research, the survival prognosis of GBM patients is unfavorable and more effective therapeutics are sorely required. Archazolid B, a potent vacuolar H{sup +}-ATPase inhibitor influencing cellular pH values, is a promising new compound exerting cytotoxicity in the nanomolar range on wild-type U87MG glioblastoma cells and U87MG.∆EGFR cells transfected with a mutant epidermal growth factor receptor (EGFR) gene. Gene expression profiling using microarray technology showed that archazolid B caused drastic disturbances in cholesterol homeostasis. Cholesterol, a main component of cellular membranes, is known to be essential for GBM growth and cells bearing EGFRvIII mutation are highly dependent on exogenous cholesterol. Archazolid B caused excessive accumulation of free cholesterol within intracellular compartments thus depleting cellular cholesterol and leading to up-regulation of SREBP targeted genes, including LDLR and HMGCR, the key enzyme of cholesterol biosynthesis. This cholesterol response is considered to be a novel resistance mechanism induced by archazolid B. We surmise that re-elevation of cholesterol levels in archazolid B treated cells may be mediated by newly synthesized cholesterol, since the drug leads to endosomal/lysosomal malfunction and cholesterol accumulation.

  20. Up-regulation of cholesterol associated genes as novel resistance mechanism in glioblastoma cells in response to archazolid B

    International Nuclear Information System (INIS)

    Treatment of glioblastoma multiforme (GBM), the most common and aggressive lethal brain tumor, represents a great challenge. Despite decades of research, the survival prognosis of GBM patients is unfavorable and more effective therapeutics are sorely required. Archazolid B, a potent vacuolar H+-ATPase inhibitor influencing cellular pH values, is a promising new compound exerting cytotoxicity in the nanomolar range on wild-type U87MG glioblastoma cells and U87MG.∆EGFR cells transfected with a mutant epidermal growth factor receptor (EGFR) gene. Gene expression profiling using microarray technology showed that archazolid B caused drastic disturbances in cholesterol homeostasis. Cholesterol, a main component of cellular membranes, is known to be essential for GBM growth and cells bearing EGFRvIII mutation are highly dependent on exogenous cholesterol. Archazolid B caused excessive accumulation of free cholesterol within intracellular compartments thus depleting cellular cholesterol and leading to up-regulation of SREBP targeted genes, including LDLR and HMGCR, the key enzyme of cholesterol biosynthesis. This cholesterol response is considered to be a novel resistance mechanism induced by archazolid B. We surmise that re-elevation of cholesterol levels in archazolid B treated cells may be mediated by newly synthesized cholesterol, since the drug leads to endosomal/lysosomal malfunction and cholesterol accumulation

  1. 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.

  2. Riddle of depleted uranium

    International Nuclear Information System (INIS)

    Depleted Uranium (DU) is the waste product of uranium enrichment from the manufacturing of fuel rods for nuclear reactors in nuclear power plants and nuclear power ships. DU may also results from the reprocessing of spent nuclear reactor fuel. Potentially DU has both chemical and radiological toxicity with two important targets organs being the kidney and the lungs. DU is made into a metal and, due to its availability, low price, high specific weight, density and melting point as well as its pyrophoricity; it has a wide range of civilian and military applications. Due to the use of DU over the recent years, there appeared in some press on health hazards that are alleged to be due to DU. In these paper properties, applications, potential environmental and health effects of DU are briefly reviewed

  3. Effects of tegaserod on bile composition and hepatic secretion in Richardson ground squirrels on an enriched cholesterol diet

    Directory of Open Access Journals (Sweden)

    Pfannkuche Hans-Juergen

    2006-06-01

    Full Text Available Abstract Background Tegaserod is effective in treating IBS patients with constipation, and does not alter gallbladder motility in healthy individuals or in patients with IBS. However, it is not known if tegaserod affects the biliary tract in gallstone disease, so to this end the effects of tegaserod on bile composition and hepatic secretion of Richardson ground squirrels maintained on an enriched cholesterol diet were examined. Results Animals were fed either a control (0.03% or enriched (1% cholesterol diet for 28 days, and treated s.c. with tegaserod (0.1 mg/kg BID or vehicle. Bile flow, bile acid, phospholipids and cholesterol secretion were measured with standard methods. Tegaserod treatment or enriched cholesterol diet, alone or combination, did not alter body or liver weights. The enriched cholesterol diet increased cholesterol saturation index (CSI, cholesterol concentrations in gallbladder and hepatic duct bile by ~50% and decreased bile acids in gallbladder bile by 17%. Tegaserod treatment reversed these cholesterol-induced changes. None of the treatments, drug or diet, altered fasting gallbladder volume, bile flow and bile salts or phospholipid secretion in normal diet and cholesterol-fed animals. However, tegaserod treatment prevented the decreases in bile acid pool size and cycling frequency caused by the enriched cholesterol diet, consequent to re-establishing normal bile acid to concentrations in the gall bladder. Tegaserod had no effect on these parameters with normal diet animals. Conclusion Tegaserod treatment results in increased enterohepatic cycling and lowers cholesterol saturation in the bile of cholesterol-fed animals. These effects would decrease conditions favorable to cholesterol gallstone formation.

  4. 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.

  5. GRP94 Regulates Circulating Cholesterol Levels through Blockade of PCSK9-Induced LDLR Degradation

    Directory of Open Access Journals (Sweden)

    Steve Poirier

    2015-12-01

    Full Text Available Clearance of circulating low-density lipoprotein cholesterol (LDLc by hepatic LDL receptors (LDLR is central for vascular health. Secreted by hepatocytes, PCSK9 induces the degradation of LDLR, resulting in higher plasma LDLc levels. Still, it remains unknown why LDLR and PCSK9 co-exist within the secretory pathway of hepatocytes without leading to complete degradation of LDLR. Herein, we identified the ER-resident GRP94, and more precisely its client-binding C-terminal domain, as a PCSK9-LDLR inhibitory binding protein. Depletion of GRP94 did not affect calcium homeostasis, induce ER stress, nor did it alter PCSK9 processing or its secretion but greatly increased its capacity to induce LDLR degradation. Accordingly, we found that hepatocyte-specific Grp94-deficient mice have higher plasma LDLc levels correlated with ∼80% reduction in hepatic LDLR protein levels. Thus, we provide evidence that, in physiological conditions, binding of PCSK9 to GRP94 protects LDLR from degradation likely by preventing early binding of PCSK9 to LDLR within the ER.

  6. Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications.

    Science.gov (United States)

    Nemes, Katriina; Åberg, Fredrik; Gylling, Helena; Isoniemi, Helena

    2016-08-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein (LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X (Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers - such as cholesterol precursor sterols, plant sterols, and cholestanol - may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation. PMID:27574546

  7. 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......The mechanism(s) underlying the sorting of integral membrane proteins between the Golgi complex and the plasma membrane remain uncertain because no specific Golgi retention signal has been found. Moreover one can alter a protein's eventual localization simply by altering the length of its...... 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...

  8. The Toxicity of Depleted Uranium

    OpenAIRE

    Wayne Briner

    2010-01-01

    Depleted uranium (DU) is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a c...

  9. 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.

  10. Regulation of biliary cholesterol secretion and reverse cholesterol transport

    NARCIS (Netherlands)

    Dikkers, Arne

    2016-01-01

    According to the World Health Organization the number one cause of death throughout the world is cardiovascular disease. Therefore, there is an urgent need for new therapeutic strategies to prevent and treat cardiovascular disease. One possible way is to target the HDL-driven reverse cholesterol tra

  11. Depleted zinc: Properties, application, production

    International Nuclear Information System (INIS)

    The addition of ZnO, depleted in the Zn-64 isotope, to the water of boiling water nuclear reactors lessens the accumulation of Co-60 on the reactor interior surfaces, reduces radioactive wastes and increases the reactor service-life because of the inhibitory action of zinc on inter-granular stress corrosion cracking. To the same effect depleted zinc in the form of acetate dihydrate is used in pressurized water reactors. Gas centrifuge isotope separation method is applied for production of depleted zinc on the industrial scale. More than 20 years of depleted zinc application history demonstrates its benefits for reduction of NPP personnel radiation exposure and combating construction materials corrosion.

  12. Depleted zinc: Properties, application, production.

    Science.gov (United States)

    Borisevich, V D; Pavlov, A V; Okhotina, I A

    2009-01-01

    The addition of ZnO, depleted in the Zn-64 isotope, to the water of boiling water nuclear reactors lessens the accumulation of Co-60 on the reactor interior surfaces, reduces radioactive wastes and increases the reactor service-life because of the inhibitory action of zinc on inter-granular stress corrosion cracking. To the same effect depleted zinc in the form of acetate dihydrate is used in pressurized water reactors. Gas centrifuge isotope separation method is applied for production of depleted zinc on the industrial scale. More than 20 years of depleted zinc application history demonstrates its benefits for reduction of NPP personnel radiation exposure and combating construction materials corrosion.

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

    Science.gov (United States)

    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 cells with increasing concentrations of lipoprotein-depleted sera (LPDS) or components present in serum as shuttles and a constant amount of LDL, small unilamellar vesicles, or red blood cells (RBC) as sinks. Synergistic efflux was measured as the difference in fractional efflux in excess of that predicted by the addition of the individual efflux values of sink and shuttle alone. Synergistic efflux was obtained when LPDS was incubated with cells and LDL. When different components of LPDS were used as shuttles, albumin produced synergistic efflux, while apoA-I did not. A synergistic effect was also obtained when RBC was used as the sink and albumin as shuttle. The previously observed negative association of albumin with coronary artery disease might be linked to reduced cholesterol shuttling that would occur when serum albumin levels are low. PMID:23288948

  14. Transcription Factor Hepatocyte Nuclear Factor-1β Regulates Renal Cholesterol Metabolism.

    Science.gov (United States)

    Aboudehen, Karam; Kim, Min Soo; Mitsche, Matthew; Garland, Kristina; Anderson, Norma; Noureddine, Lama; Pontoglio, Marco; Patel, Vishal; Xie, Yang; DeBose-Boyd, Russell; Igarashi, Peter

    2016-08-01

    HNF-1β is a tissue-specific transcription factor that is expressed in the kidney and other epithelial organs. Humans with mutations in HNF-1β develop kidney cysts, and HNF-1β regulates the transcription of several cystic disease genes. However, the complete spectrum of HNF-1β-regulated genes and pathways is not known. Here, using chromatin immunoprecipitation/next generation sequencing and gene expression profiling, we identified 1545 protein-coding genes that are directly regulated by HNF-1β in murine kidney epithelial cells. Pathway analysis predicted that HNF-1β regulates cholesterol metabolism. Expression of dominant negative mutant HNF-1β or kidney-specific inactivation of HNF-1β decreased the expression of genes that are essential for cholesterol synthesis, including sterol regulatory element binding factor 2 (Srebf2) and 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr). HNF-1β mutant cells also expressed lower levels of cholesterol biosynthetic intermediates and had a lower rate of cholesterol synthesis than control cells. Additionally, depletion of cholesterol in the culture medium mitigated the inhibitory effects of mutant HNF-1β on the proteins encoded by Srebf2 and Hmgcr, and HNF-1β directly controlled the renal epithelial expression of proprotein convertase subtilisin-like kexin type 9, a key regulator of cholesterol uptake. These findings reveal a novel role of HNF-1β in a transcriptional network that regulates intrarenal cholesterol metabolism. PMID:26712526

  15. Dietary Cholesterol Promotes Adipocyte Hypertrophy and Adipose Tissue Inflammation in Visceral, But Not Subcutaneous, Fat in Monkeys

    Science.gov (United States)

    Chung, Soonkyu; Cuffe, Helen; Marshall, Stephanie M.; McDaniel, Allison L.; Ha, Jung-Heun; Kavanagh, Kylie; Hong, Cynthia; Tontonoz, Peter; Temel, Ryan E.; Parks, John S

    2014-01-01

    Objective Excessive caloric intake is associated with obesity and adipose tissue dysfunction. However, the role of dietary cholesterol in this process is unknown. The aim of this study was to determine whether increasing dietary cholesterol intake alters adipose tissue cholesterol content, adipocyte size, and endocrine function in nonhuman primates. Approach and Results Age-matched, male African Green monkeys (n=5 per group) were assigned to one of three diets containing 0.002 (Lo), 0.2 (Med) or 0.4 (Hi) mg cholesterol/Kcal. After 10 weeks of diet feeding, animals were euthanized for adipose tissue, liver, and plasma collection. With increasing dietary cholesterol, free cholesterol (FC) content and adipocyte size increased in a step-wise manner in visceral, but not subcutaneous fat, with a significant association between visceral adipocyte size and FC content (r2=0.298; n=15; p=0.035). In visceral fat, dietary cholesterol intake was associated with: 1) increased pro-inflammatory gene expression and macrophage recruitment, 2) decreased expression of genes involved in cholesterol biosynthesis and lipoprotein uptake, and 3) increased expression of proteins involved in FC efflux. Conclusions Increasing dietary cholesterol selectively increases visceral fat adipocyte size, FC and macrophage content, and proinflammatory gene expression in nonhuman primates. Visceral fat cells appear to compensate for increased dietary cholesterol by limiting cholesterol uptake/synthesis and increasing FC efflux pathways. PMID:24969772

  16. 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

  17. Impact of SCP-2/SCP-x gene ablation and dietary cholesterol on hepatic lipid accumulation.

    Science.gov (United States)

    Klipsic, Devon; Landrock, Danilo; Martin, Gregory G; McIntosh, Avery L; Landrock, Kerstin K; Mackie, John T; Schroeder, Friedhelm; Kier, Ann B

    2015-09-01

    While a high-cholesterol diet induces hepatic steatosis, the role of intracellular sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x) proteins is unknown. We hypothesized that ablating SCP-2/SCP-x [double knockout (DKO)] would impact hepatic lipids (cholesterol and cholesteryl ester), especially in high-cholesterol-fed mice. DKO did not alter food consumption, and body weight (BW) gain decreased especially in females, concomitant with hepatic steatosis in females and less so in males. DKO-induced steatosis in control-fed wild-type (WT) mice was associated with 1) loss of SCP-2; 2) upregulation of liver fatty acid binding protein (L-FABP); 3) increased mRNA and/or protein levels of sterol regulatory element binding proteins (SREBP1 and SREBP2) as well as increased expression of target genes of cholesterol synthesis (Hmgcs1 and Hmgcr) and fatty acid synthesis (Acc1 and Fas); and 4) cholesteryl ester accumulation was also associated with increased acyl-CoA cholesterol acyltransferase-2 (ACAT2) in males. DKO exacerbated the high-cholesterol diet-induced hepatic cholesterol and glyceride accumulation, without further increasing SREBP1, SREBP2, or target genes. This exacerbation was associated both with loss of SCP-2 and concomitant downregulation of Ceh/Hsl, apolipoprotein B (ApoB), MTP, and/or L-FABP protein expression. DKO diminished the ability to secrete excess cholesterol into bile and oxidize cholesterol to bile acid for biliary excretion, especially in females. This suggested that SCP-2/SCP-x affects cholesterol transport to particular intracellular compartments, with ablation resulting in less to the endoplasmic reticulum for SREBP regulation, making more available for cholesteryl ester synthesis, for cholesteryl-ester storage in lipid droplets, and for bile salt synthesis and/or secretion. These alterations are significant findings, since they affect key processes in regulation of sterol metabolism. PMID:26113298

  18. Depletable resources and the economy.

    NARCIS (Netherlands)

    Heijman, W.J.M.

    1991-01-01

    The subject of this thesis is the depletion of scarce resources. The main question to be answered is how to avoid future resource crises. After dealing with the complex relation between nature and economics, three important concepts in relation with resource depletion are discussed: steady state, ti

  19. Stratospheric ozone depletion.

    Science.gov (United States)

    Rowland, F Sherwood

    2006-05-29

    Solar ultraviolet radiation creates an ozone layer in the atmosphere which in turn completely absorbs the most energetic fraction of this radiation. This process both warms the air, creating the stratosphere between 15 and 50 km altitude, and protects the biological activities at the Earth's surface from this damaging radiation. In the last half-century, the chemical mechanisms operating within the ozone layer have been shown to include very efficient catalytic chain reactions involving the chemical species HO, HO2, NO, NO2, Cl and ClO. The NOX and ClOX chains involve the emission at Earth's surface of stable molecules in very low concentration (N2O, CCl2F2, CCl3F, etc.) which wander in the atmosphere for as long as a century before absorbing ultraviolet radiation and decomposing to create NO and Cl in the middle of the stratospheric ozone layer. The growing emissions of synthetic chlorofluorocarbon molecules cause a significant diminution in the ozone content of the stratosphere, with the result that more solar ultraviolet-B radiation (290-320 nm wavelength) reaches the surface. This ozone loss occurs in the temperate zone latitudes in all seasons, and especially drastically since the early 1980s in the south polar springtime-the 'Antarctic ozone hole'. The chemical reactions causing this ozone depletion are primarily based on atomic Cl and ClO, the product of its reaction with ozone. The further manufacture of chlorofluorocarbons has been banned by the 1992 revisions of the 1987 Montreal Protocol of the United Nations. Atmospheric measurements have confirmed that the Protocol has been very successful in reducing further emissions of these molecules. Recovery of the stratosphere to the ozone conditions of the 1950s will occur slowly over the rest of the twenty-first century because of the long lifetime of the precursor molecules. PMID:16627294

  20. 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

  1. 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 ...

  2. Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases

    OpenAIRE

    Vance, Jean E.

    2012-01-01

    Dysregulation of cholesterol homeostasis in the brain is increasingly being linked to chronic neurodegenerative disorders, including Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), Niemann-Pick type C (NPC) disease and Smith-Lemli Opitz syndrome (SLOS). However, the molecular mechanisms underlying the correlation between altered cholesterol metabolism and the neurological deficits are, for the most part, not clear. NPC disease and SLOS are caused by mutations in...

  3. Slow intestinal transit: a motor disorder contributing to cholesterol gallstone formation in the ground squirrel.

    Science.gov (United States)

    Xu, Q W; Scott, R B; Tan, D T; Shaffer, E A

    1996-06-01

    Impaired gallbladder motility is an established factor in cholesterol gallstone formation. We assessed whether altered small intestinal smooth muscle contractility with slow transit might potentiate gallstone formation by further impeding enterohepatic cycling of bile acids. Ground squirrels were fed a 1% or a trace (controls) cholesterol diet. Small intestinal transit was evaluated from 51Cr distribution in conscious, fasted animals 20 minutes after infusion into the proximal jejunum. Small intestinal and gallbladder smooth muscle contractility was determined in vitro. Biliary lipid secretion was measured from the cannulated common duct and the bile salt pool size calculated by isotope dilution. Gas-liquid chromatography (GLC) assessed bile salt profile. In animals on the 1% cholesterol diet, aboral transit was significantly delayed, the maximal contractile response to bethanechol was markedly increased (P <.05) with no change in median effective concentration in either circular or longitudinal muscle strips from both the jejunum and ileum, and the gallbladder contractile responses to bethanechol and cholecystokinin (CCK) were decreased. Cholesterol saturation index and the fraction of deoxycholic acid in the pool doubled, whereas the total bile salt pool size remained unchanged in cholesterol-fed animals. In this model, a high-cholesterol diet is associated with altered small intestinal smooth muscle contractility and prolonged small intestinal transit, in addition to diminished gallbladder contractility. The resulting sluggish enterohepatic cycling of bile salts, associated with expanded deoxycholate pool, contributes to cholesterol gallstone formation. PMID:8675191

  4. Analysis of Cholesterol Trafficking with Fluorescent Probes

    DEFF Research Database (Denmark)

    Maxfield, Frederick R.; Wustner, Daniel

    2012-01-01

    Cholesterol plays an important role in determining the biophysical properties of biological membranes, and its concentration is tightly controlled by homeostatic processes. The intracellular transport of cholesterol among organelles is a key part of the homeostatic mechanism, but sterol transport...... 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...

  5. 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 ...

  6. Alterations of pulmonary defense mechanisms by protein depletion diet.

    OpenAIRE

    Jakab, G J; Warr, G A; Astry, C L

    1981-01-01

    Pulmonary defense mechanisms were quantitated in mice that were fed a protein-free diet (PFD) for periods of 2 and 3 weeks. Despite the severe weight loss and emaciation induced by the diet, the bactericidal mechanisms in their lungs were preserved against aerogenic challenges with staphylococcus aureus, Proteus mirabilis, and Listeria monocytogenes. Phagocytic assays of alveolar macrophages that were retrieved by pulmonary lavage from PFD-fed animals showed a decrease in Fc receptor-mediated...

  7. Observations of ozone depletion associated with solar proton events

    Science.gov (United States)

    Mcpeters, R. D.; Jackman, C. H.; Stassinopoulos, E. G.

    1981-01-01

    Ozone profiles from the solar proton events (SPE) of January and September 1971 and August 1972 were obtained after the backscattered ultraviolet (BUV) measured radiances were corrected for the direct effects of protons on the instrument. The SPE of August 1972 produced an ozone depletion of 15% at 42 km that persisted for one month in both northern and southern polar regions. This long recovery time indicates that NO(x) was produced in a quantity sufficient to alter the ozone chemistry. The two SPE in 1971 were of moderate size, but produced ozone depletions of 10-30% at 50 km with a 36 hour recovery time. This rapid recovery is consistent with the assumption that HO(x) is responsible for altering the ozone chemistry (Weeks et al., 1972). The magnitude of the observed depletion, however, exceeds that predicted by the chemical models.

  8. 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

  9. 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…

  10. Public health aspects of serum cholesterol

    NARCIS (Netherlands)

    S. Houterman (Saskia)

    2001-01-01

    textabstractIn the beginning of this century Anitschkow and De Langen started pioneering work concerning the relation between cholesterol and coronary heart disease. Both showed that there was a possible relation between cholesterol in the diet, blood cholesterol levels and atherosclerosis. It took

  11. 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...

  12. 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 ...

  13. Cholesterol Screening: A Practical Guide to Implementation.

    Science.gov (United States)

    Kingery, Paul M.

    1995-01-01

    Dry-chemistry cholesterol analysis has made screening feasible in a variety of settings. The article provides practical tips for the implementation of mass cholesterol screening using a portable dry-chemistry analyzer and discusses issues involved in conducting effective cholesterol screening programs from start to finish. (SM)

  14. 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.

  15. Testing fully depleted CCD

    Science.gov (United States)

    Casas, Ricard; Cardiel-Sas, Laia; Castander, Francisco J.; Jiménez, Jorge; de Vicente, Juan

    2014-08-01

    The focal plane of the PAU camera is composed of eighteen 2K x 4K CCDs. These devices, plus four spares, were provided by the Japanese company Hamamatsu Photonics K.K. with type no. S10892-04(X). These detectors are 200 μm thick fully depleted and back illuminated with an n-type silicon base. They have been built with a specific coating to be sensitive in the range from 300 to 1,100 nm. Their square pixel size is 15 μm. The read-out system consists of a Monsoon controller (NOAO) and the panVIEW software package. The deafualt CCD read-out speed is 133 kpixel/s. This is the value used in the calibration process. Before installing these devices in the camera focal plane, they were characterized using the facilities of the ICE (CSIC- IEEC) and IFAE in the UAB Campus in Bellaterra (Barcelona, Catalonia, Spain). The basic tests performed for all CCDs were to obtain the photon transfer curve (PTC), the charge transfer efficiency (CTE) using X-rays and the EPER method, linearity, read-out noise, dark current, persistence, cosmetics and quantum efficiency. The X-rays images were also used for the analysis of the charge diffusion for different substrate voltages (VSUB). Regarding the cosmetics, and in addition to white and dark pixels, some patterns were also found. The first one, which appears in all devices, is the presence of half circles in the external edges. The origin of this pattern can be related to the assembly process. A second one appears in the dark images, and shows bright arcs connecting corners along the vertical axis of the CCD. This feature appears in all CCDs exactly in the same position so our guess is that the pattern is due to electrical fields. Finally, and just in two devices, there is a spot with wavelength dependence whose origin could be the result of a defectous coating process.

  16. The role of cholesterol-sphingomyelin membrane nanodomains in the stability of intercellular membrane nanotubes

    Directory of Open Access Journals (Sweden)

    Veranič P

    2012-04-01

    Full Text Available Maruša Lokar1,*, Doron Kabaso1,2,*, Nataša Resnik3, Kristina Sepcic5, Veronika Kralj-Iglic4,6, Peter Veranic3, Robert Zorec2, Aleš Iglic1,6 1Laboratory of Biophysics, Faculty of Electrical Engineering, 2Laboratory of Neuroendocrinology-Molecular Cell Physiology, Faculty of Medicine, 3Institute of Cell Biology, Faculty of Medicine, 4Faculty of Health Sciences, 5Department of Biology, Biotechnical Faculty, 6Laboratory of Clinical Biophysics, Department of Orthopedic Surgery, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia*These authors equally share first authorshipAbstract: Intercellular membrane nanotubes (ICNs are highly curved tubular structures that connect neighboring cells. The stability of these structures depends on the inner cytoskeleton and the cell membrane composition. Yet, due to the difficulty in the extraction of ICNs, the cell membrane composition remains elusive. In the present study, a raft marker, ostreolysin, revealed the enrichment of cholesterol-sphingomyelin membrane nanodomains along ICNs in a T24 (malignant urothelial cancer cell line. Cholesterol depletion, due to the addition of methyl-β-cyclodextrin, caused the dispersion of cholesterol-sphingomyelin membrane nanodomains and the retraction of ICNs. The depletion of cholesterol also led to cytoskeleton reorganization and to formation of actin stress fibers. Live cell imaging data revealed the possible functional coupling between the change from polygonal to spherical shape, cell separation, and the disconnection of ICNs. The ICN was modeled as an axisymmetric tubular structure, enabling us to investigate the effects of cholesterol content on the ICN curvature. The removal of cholesterol was predicted to reduce the positive spontaneous curvature of the remaining membrane components, increasing their curvature mismatch with the tube curvature. The mechanisms by which the increased curvature mismatch could contribute to the disconnection of ICNs are

  17. Relationship between plasma cholesterol levels and cholesterol esterification in isolated human mononuclear cells

    Energy Technology Data Exchange (ETDEWEB)

    Dallongeville, J.; Davignon, J.; Lussier-Cacan, S. (Clinical Research Institute of Montreal, Quebec (Canada))

    1990-01-01

    The authors studied the relationship between plasma lipoprotein concentrations and cholesterol esterification in freshly isolated human mononuclear cells from 27 normolipidemic and 32 hyperlipidemic individuals. Cells were either incubated for 5 hours with radiolabeled oleate immediately after isolation or were preincubated for 18 hours in the presence of exogenous cholesterol, and then incubated with ({sup 14}C)sodium-oleate-albumin complex. In the absence of exogenous cholesterol, control and hypercholesterolemic subjects had similarly low values of intracellular cholesterol esterification. In the presence of exogenous cholesterol, both hypertriglyceridemic and hypercholesterolemic subjects had higher cholesterol esterification than controls. There was a significant correlation between the rate of cholesterol esterification and plasma total cholesterol. These results suggest that plasma cholesterol levels may regulate mononuclear cell intra-cellular cholesterol esterification in humans.

  18. Biliary cholesterol secretion : More than a simple ABC

    NARCIS (Netherlands)

    Dikkers, Arne; Tietge, Uwe J. F.

    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 final step for the elimination of cholesterol originat

  19. Fish protein hydrolysates affect cholesterol metabolism in rats fed non-cholesterol and high-cholesterol diets.

    Science.gov (United States)

    Hosomi, Ryota; Fukunaga, Kenji; Arai, Hirofumi; Kanda, Seiji; Nishiyama, Toshimasa; Yoshida, Munehiro

    2012-03-01

    Fish consumption is well known to provide health benefits in both experimental animals and human subjects. Numerous studies have demonstrated the beneficial effects of various protein hydrolysates on lipid metabolism. In this context, this study examined the effect of fish protein hydrolysates (FPH) on cholesterol metabolism compared with the effect of casein. FPHs were prepared from Alaska pollock meat using papain as a protease. Male Wistar rats were divided into the following four dietary groups of seven rats each: either casein (20%) or FPH (10%) + casein (10%), with or without 0.5% cholesterol and 0.1% sodium cholate. Serum and liver lipid levels, fecal cholesterol and bile acid excretions, and the hepatic expression of genes encoding proteins involved in cholesterol homeostasis were examined. In rats fed the FPH diets compared with casein diets with or without cholesterol and sodium cholate, the indexes of cholesterol metabolism-namely, serum cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels-were significantly lower, whereas fecal cholesterol and bile acid excretions were higher. Rats fed the FPH diets compared with casein with cholesterol exhibited a lower liver cholesterol level via an increased liver cholesterol 7α-hydroxylase (CYP7A1) expression level. This study demonstrates that the intake of FPH has hypocholesterolemic effects through the enhancement of fecal cholesterol and bile acid excretions and CYP7A1 expression levels. Therefore, fish peptides prepared by papain digestion might provide health benefits by decreasing the cholesterol content in the blood, which would contribute to the prevention of circulatory system diseases such as arteriosclerosis. PMID:22181072

  20. 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...

  1. Peptide mediators of cholesterol efflux

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. 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.

  3. 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...

  4. Intracellular transport of cholesterol in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Brasaemle, D.L.

    1989-01-01

    The erythrocyte was selected as a simple cell for the study of transbilayer movement of cholesterol. Cholesterol oxidase was used to measure the distribution of ({sup 3}H)cholesterol across the erythrocyte membrane. Cholesterol oxidase was also used to estimate the rate of transport of low density lipoprotein (LDL) cholesterol to the plasma membrane of cultured Chinese hamster ovary (CHO) fibroblasts; the half-time of this process was 42 minutes. The rate of transport of LDL cholesterol to the plasma membrane was confirmed by a second procedure using amphotericin B. Amphotericin B was also used to estimate the rate of transport of endogenously synthesized cholesterol to the plasma membrane of CHO cells. New methodology was developed including improvements of the previously published cholesterol oxidase assay for plasma membrane cholesterol. A new method for detecting transport of cholesterol to the plasma membrane in cultured cells was developed using amphotericin B. Preliminary studies investigated the use of fluorescent polyenes, pimaricin and etruscomycin, as probes for plasma membrane cholesterol in transport studies. Finally, a modification of a previously published cell staining protocol yielded a simple, quantitative assay for cell growth.

  5. Regulation of the high-affinity choline transporter activity and trafficking by its association with cholesterol-rich lipid rafts.

    Science.gov (United States)

    Cuddy, Leah K; Winick-Ng, Warren; Rylett, Rebecca Jane

    2014-03-01

    The sodium-coupled, hemicholinium-3-sensitive, high-affinity choline transporter (CHT) is responsible for transport of choline into cholinergic nerve terminals from the synaptic cleft following acetylcholine release and hydrolysis. In this study, we address regulation of CHT function by plasma membrane cholesterol. We show for the first time that CHT is concentrated in cholesterol-rich lipid rafts in both SH-SY5Y cells and nerve terminals from mouse forebrain. Treatment of SH-SY5Y cells expressing rat CHT with filipin, methyl-β-cyclodextrin (MβC) or cholesterol oxidase significantly decreased choline uptake. In contrast, CHT activity was increased by addition of cholesterol to membranes using cholesterol-saturated MβC. Kinetic analysis of binding of [(3)H]hemicholinium-3 to CHT revealed that reducing membrane cholesterol with MβC decreased both the apparent binding affinity (KD) and maximum number of binding sites (Bmax ); this was confirmed by decreased plasma membrane CHT protein in lipid rafts in cell surface protein biotinylation assays. Finally, the loss of cell surface CHT associated with lipid raft disruption was not because of changes in CHT internalization. In summary, we provide evidence that CHT association with cholesterol-rich rafts is critical for transporter function and localization. Alterations in plasma membrane cholesterol cholinergic nerve terminals could diminish cholinergic transmission by reducing choline availability for acetylcholine synthesis. The sodium-coupled choline transporter CHT moves choline into cholinergic nerve terminals to serve as substrate for acetylcholine synthesis. We show for the first time that CHT is concentrated in cholesterol-rich lipid rafts, and decreasing membrane cholesterol significantly reduces both choline uptake activity and cell surface CHT protein levels. CHT association with cholesterol-rich rafts is critical for its function, and alterations in plasma membrane cholesterol could diminish cholinergic

  6. The effects of apolipoprotein F deficiency on high density lipoprotein cholesterol metabolism in mice.

    Directory of Open Access Journals (Sweden)

    William R Lagor

    Full Text Available Apolipoprotein F (apoF is 29 kilodalton secreted sialoglycoprotein that resides on the HDL and LDL fractions of human plasma. Human ApoF is also known as Lipid Transfer Inhibitor protein (LTIP based on its ability to inhibit cholesteryl ester transfer protein (CETP-mediated transfer events between lipoproteins. In contrast to other apolipoproteins, ApoF is predicted to lack strong amphipathic alpha helices and its true physiological function remains unknown. We previously showed that overexpression of Apolipoprotein F in mice reduced HDL cholesterol levels by 20-25% by accelerating clearance from the circulation. In order to investigate the effect of physiological levels of ApoF expression on HDL cholesterol metabolism, we generated ApoF deficient mice. Unexpectedly, deletion of ApoF had no substantial impact on plasma lipid concentrations, HDL size, lipid or protein composition. Sex-specific differences were observed in hepatic cholesterol content as well as serum cholesterol efflux capacity. Female ApoF KO mice had increased liver cholesteryl ester content relative to wild type controls on a chow diet (KO: 3.4+/-0.9 mg/dl vs. WT: 1.2+/-0.3 mg/dl, p<0.05. No differences were observed in ABCG1-mediated cholesterol efflux capacity in either sex. Interestingly, ApoB-depleted serum from male KO mice was less effective at promoting ABCA1-mediated cholesterol efflux from J774 macrophages relative to WT controls.

  7. Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Jean E. Vance

    2012-11-01

    Full Text Available Dysregulation of cholesterol homeostasis in the brain is increasingly being linked to chronic neurodegenerative disorders, including Alzheimer’s disease (AD, Huntington’s disease (HD, Parkinson’s disease (PD, Niemann-Pick type C (NPC disease and Smith-Lemli Opitz syndrome (SLOS. However, the molecular mechanisms underlying the correlation between altered cholesterol metabolism and the neurological deficits are, for the most part, not clear. NPC disease and SLOS are caused by mutations in genes involved in the biosynthesis or intracellular trafficking of cholesterol, respectively. However, the types of neurological impairments, and the areas of the brain that are most affected, differ between these diseases. Some, but not all, studies indicate that high levels of plasma cholesterol correlate with increased risk of developing AD. Moreover, inheritance of the E4 isoform of apolipoprotein E (APOE, a cholesterol-carrying protein, markedly increases the risk of developing AD. Whether or not treatment of AD with statins is beneficial remains controversial, and any benefit of statin treatment might be due to anti-inflammatory properties of the drug. Cholesterol balance is also altered in HD and PD, although no causal link between dysregulated cholesterol homeostasis and neurodegeneration has been established. Some important considerations for treatment of neurodegenerative diseases are the impermeability of the blood-brain barrier to many therapeutic agents and difficulties in reversing brain damage that has already occurred. This article focuses on how cholesterol balance in the brain is altered in several neurodegenerative diseases, and discusses some commonalities and differences among the diseases.

  8. Depletable resources and the economy.

    OpenAIRE

    Heijman, W. J. M.

    1991-01-01

    The subject of this thesis is the depletion of scarce resources. The main question to be answered is how to avoid future resource crises. After dealing with the complex relation between nature and economics, three important concepts in relation with resource depletion are discussed: steady state, time preference and efficiency.For the steady state, three variants are distinguished; the stationary state, the physical steady state and the state of steady growth. It is concluded that the so-call...

  9. Phosphorus demand for the 1970-2100 period: A scenario analysis of resource depletion

    NARCIS (Netherlands)

    Vuuren, van D.P.; Bouwman, A.F.; Beusen, A.H.W.

    2010-01-01

    The phosphorus (P) cycle has been significantly altered by human activities. For this paper, we explored the sustainability of current P flows in terms of resource depletion and the ultimate fate of these flows. The analysis shows that rapid depletion of extractable phosphate rock is not very likely

  10. Mechanism of the hepatic lipase induced accumulation of high-density lipoprotein cholesterol by cells in culture

    International Nuclear Information System (INIS)

    Hepatic lipase can enhance the delivery of high-density lipoprotein (HDL) cholesterol to cells by a process which does not involve apoprotein catabolism. The incorporation of HDL-free (unesterified) cholesterol, phospholipid, and cholesteryl ester by cells has been compared to establish the mechanism of this delivery process. Human HDL was reconstituted with 3H-free cholesterol and [14C]sphingomyelin, treated with hepatic lipase in the presence of albumin to remove the products of lipolysis, reisolated, and then incubated with cultured rat hepatoma cells. Relative to control HDL, modification of HDL with hepatic lipase stimulated both the amount of HDL-free cholesterol taken up by the cell and the esterification of HDL-free cholesterol but did not affect the delivery of sphingomyelin. Experiments utilizing HDL reconstituted with 14C-free cholesterol and [3H]cholesteryl oleoyl ether suggest that hepatic lipase enhances the incorporation of HDL-esterified cholesterol. However, the amount of free cholesterol delivered as a result of treatment with hepatic lipase was 4-fold that of esterified cholesterol. On the basis of HDL composition, the cellular incorporation of free cholesterol was about 10 times that which would occur by the uptake and degradation of intact particles. The preferential incorporation of HDL-free cholesterol did not require the presence of lysophosphatidylcholine. To correlate the events observed at the cellular level with alterations in lipoprotein structure, high-resolution, proton-decoupled 13C nuclear magnetic resonance spectroscopy (90.55 MHz) was performed on HDL3 in which the cholesterol molecules were replaced with [4-13C]cholesterol by particle reconstitution

  11. The TMAO-Generating Enzyme Flavin Monooxygenase 3 Is a Central Regulator of Cholesterol Balance

    Directory of Open Access Journals (Sweden)

    Manya Warrier

    2015-01-01

    Full Text Available Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide (TMAO have recently been linked to cardiovascular disease (CVD risk. Here, we performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3 as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic endoplasmic reticulum (ER stress and inflammation in part by decreasing hepatic oxysterol levels and subsequent LXR activation. FMO3 is thus identified as a central integrator of hepatic cholesterol and triacylglycerol metabolism, inflammation, and ER stress. These studies suggest that the gut microbiota-driven TMA/FMO3/TMAO pathway is a key regulator of lipid metabolism and inflammation.

  12. Influence of cholesterol content on red cell membrane viscoelasticity and fluidity.

    OpenAIRE

    Chabanel, A; Flamm, M.; Sung, K L; Lee, M. M.; Schachter, D; Chien, S

    1983-01-01

    The purpose of this investigation was to correlate the viscoelastic properties and lipid fluidity of the red blood cell membrane to its lipid composition. The viscoelastic properties of human red cells that had been enriched or depleted in cholesterol were determined by the micropipette technique. The lipid fluidity of the outer and inner leaflets of the erythrocyte membrane was concurrently assessed by steady state fluorescence depolarization. The elastic modulus and the viscosity moduli of ...

  13. Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models.

    Science.gov (United States)

    Laplante, Marc-André; Charbonneau, Alexandre; Avramoglu, Rita Kohen; Pelletier, Patricia; Fang, Xiangping; Bachelard, Hélène; Ylä-Herttuala, Seppo; Laakso, Markku; Després, Jean-Pierre; Deshaies, Yves; Sweeney, Gary; Mathieu, Patrick; Marette, André

    2013-09-01

    Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation, and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr(-/-) ApoB(100/100) (LRKOB100) and atherosclerotic/diabetic IGF-II × LDLr(-/-) ApoB(100/100) (LRKOB100/IGF) mice. Each group was fed either a standard chow diet, a 0.2% cholesterol diet, a high-fat diet (HFD), or a high-fat 0.2% cholesterol diet for 6 mo. The triglyceride-rich HFD increased body weight, glucose intolerance, and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol, however, increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis.

  14. Inhibition of HMG CoA reductase reveals an unexpected role for cholesterol during PGC migration in the mouse

    Directory of Open Access Journals (Sweden)

    Ewing Andrew G

    2008-12-01

    Full Text Available Abstract Background Primordial germ cells (PGCs are the embryonic precursors of the sperm and eggs. Environmental or genetic defects that alter PGC development can impair fertility or cause formation of germ cell tumors. Results We demonstrate a novel role for cholesterol during germ cell migration in mice. Cholesterol was measured in living tissue dissected from mouse embryos and was found to accumulate within the developing gonads as germ cells migrate to colonize these structures. Cholesterol synthesis was blocked in culture by inhibiting the activity of HMG CoA reductase (HMGCR resulting in germ cell survival and migration defects. These defects were rescued by co-addition of isoprenoids and cholesterol, but neither compound alone was sufficient. In contrast, loss of the last or penultimate enzyme in cholesterol biosynthesis did not alter PGC numbers or position in vivo. However embryos that lack these enzymes do not exhibit cholesterol defects at the stage at which PGCs are migrating. This demonstrates that during gestation, the cholesterol required for PGC migration can be supplied maternally. Conclusion In the mouse, cholesterol is required for PGC survival and motility. It may act cell-autonomously by regulating clustering of growth factor receptors within PGCs or non cell-autonomously by controlling release of growth factors required for PGC guidance and survival.

  15. Nonlinear lower hybrid wave depletion

    International Nuclear Information System (INIS)

    Two numerical ray tracing codes with focusing are used to compute lower hybrid daughter wave amplification by quasi-mode parametric decay. The first code, LHPUMP provides a numerical pump model on a grid. This model is used by a second code, LHFQM which computes daughter wave amplification inside the pump extent and follows the rays until their energy is absorbed by the plasma. An analytic model is then used to estimate pump depletion based on the numerical results. Results for PLT indicate strong pump depletion at the plasma edge at high density operation for the 800 Mhz wave frequency, but weak depletion for the 2.45 Ghz experiment. This is proposed to be the mechanism responsible for the high density limit for current drive as well as for the difficulty to heat ions

  16. 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...

  17. Lp(a-cholesterol is associated with HDL-cholesterol in overweight and obese African American children and is not an independent risk factor for CVD

    Directory of Open Access Journals (Sweden)

    Sharma Sushma

    2012-01-01

    Full Text Available Abstract Background The role of Lipoprotein (a cholesterol {Lp(a-C}as an additional and/or independent risk factor for cardiovascular disease (CVD is not clear. We evaluated the associations between Lp(a-C and other CVD risk factors including plasma lipoprotein concentrations and body fatness in overweight and obese African American children. Methods A cross-sectional analysis was carried out using data from a sample of 121 African American children aged 9-11 years with Body Mass Index (BMI's greater than the 85th percentile. Body height, weight and waist circumference (WC were measured. Fasting plasma concentrations of Lp(a-C, Total cholesterol (TC, High density lipoprotein cholesterol (HDL-C, Very low density lipoprotein cholesterol (VLDL-C, Intermediate density lipoprotein cholesterol (IDL-C, Low density lipoprotein cholesterol (LDL-C, and Triacylglycerides (TAG were analyzed using the vertical auto profile (VAP cholesterol method. Results After adjusting for child age, gender, and pubertal status, Lp(a-C was positively associated with both HDL-C and TC, and negatively associated with VLDL-C and TAG. Including BMIz and WC as additional covariates did not alter the direction of the relationships between Lp(a-C and the other lipoproteins. Finally, after adjusting for the other plasma lipoproteins, Lp(a-C remained strongly associated with HDL-C, whereas the associations of Lp(a-C with the other lipoproteins were not significant when HDL-C was simultaneously included in the regression models. Conclusions Lp(a-C was positively associated with HDL-C and this association is not influenced by other lipoprotein subclasses or by the degree of obesity. We conclude that Lp(a cholesterol is not an independent risk factor for CVD in African American children.

  18. 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.

  19. Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins.

    Science.gov (United States)

    Duangjai, Acharaporn; Ingkaninan, Kornkanok; Praputbut, Sakonwun; Limpeanchob, Nanteetip

    2013-04-01

    Black pepper (Piper nigrum L.) lowers blood lipids in vivo and inhibits cholesterol uptake in vitro, and piperine may mediate these effects. To test this, the present study aimed to compare actions of black pepper extract and piperine on (1) cholesterol uptake and efflux in Caco-2 cells, (2) the membrane/cytosol distribution of cholesterol transport proteins in these cells, and (3) the physicochemical properties of cholesterol micelles. Piperine or black pepper extract (containing the same amount of piperine) dose-dependently reduced cholesterol uptake into Caco-2 cells in a similar manner. Both preparations reduced the membrane levels of NPC1L1 and SR-BI proteins but not their overall cellular expression. Micellar cholesterol solubility of lipid micelles was unaffected except by 1 mg/mL concentration of black pepper extract. These data suggest that piperine is the active compound in black pepper and reduces cholesterol uptake by internalizing the cholesterol transporter proteins.

  20. 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...

  1. 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,...

  2. 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 ...

  3. POSSIBILITIES FOR THE REDUCTION OF FAT AND CHOLESTEROL LEVEL IN MEAT ANIMALS

    Directory of Open Access Journals (Sweden)

    Slavko Čepin

    2000-06-01

    Full Text Available The majority of consumers refuse meat with higher levels of fat, because of possible association between high levels of saturated fat, cholesterol and heart disease. The meat production tries to fit consumers preferences with lowering fat content of meat. Such meat should also contain less cholesterol. In the following contribution the possibilities for reducing fat and cholesterol content and altering fatty acid composition of meat are discussed. In meat animals the estimated heritability for fat content is relatively high (between 0.3 and 0.6. This means that selection represents a powerful tool for fat reduction. Even better possibility for reducing fat and altering fatty acid composition is adequate nutrition. The decrease of animal age and weight at slaughter can also reduce carcass fat content. Also the use of transgenic animals and different growth stimulators represents a wide range of possibilities to reduce fat content in farm animals.

  4. 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

  5. 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

  6. 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

  7. 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

  8. Cholesterol oxidation products. Their occurrence and detection in our foodstuffs.

    Science.gov (United States)

    Yan, P S

    1999-01-01

    The structural similarity of cholesterol oxidation products (COP) to native cholesterol and their xenobiotic effects prompt researchers to study the long-term effects of the assimilation of these compounds into our tissues. COP are present in our food system. The level of exposure changes as our food products and our food choices alter. Therefore, the presence of COP in our food system has to be carefully monitored and their presence in processed foods minimized by optimizing processing and storage conditions. This review will briefly discuss the chemistry of some commonly-occurring COP and their biological significance. A more in-depth survey of the literature on the pitfalls of COP determination is included. It is the intention of the author to impress the readers that 'exogenous' COP can easily form during sample preparation. These artifacts will hinder our understanding of factors that promote COP formation in foods. The effects of heating, dehydrating, packaging and the presence of highly unsaturated lipids on the levels of COP in cholesterol-containing foods are evaluated to gauge the levels of exposure to different consumer groups.

  9. C57Bl/6 N mice on a western diet display reduced intestinal and hepatic cholesterol levels despite a plasma hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Desmarchelier Charles

    2012-03-01

    Full Text Available Abstract Background Small intestine and liver greatly contribute to whole body lipid, cholesterol and phospholipid metabolism but to which extent cholesterol and phospholipid handling in these tissues is affected by high fat Western-style obesogenic diets remains to be determined. Methods We therefore measured cholesterol and phospholipid concentration in intestine and liver and quantified fecal neutral sterol and bile acid excretion in C57Bl/6 N mice fed for 12 weeks either a cholesterol-free high carbohydrate control diet or a high fat Western diet containing 0.03% (w/w cholesterol. To identify the underlying mechanisms of dietary adaptations in intestine and liver, changes in gene expression were assessed by microarray and qPCR profiling, respectively. Results Mice on Western diet showed increased plasma cholesterol levels, associated with the higher dietary cholesterol supply, yet, significantly reduced cholesterol levels were found in intestine and liver. Transcript profiling revealed evidence that expression of numerous genes involved in cholesterol synthesis and uptake via LDL, but also in phospholipid metabolism, underwent compensatory regulations in both tissues. Alterations in glycerophospholipid metabolism were confirmed at the metabolite level by phospolipid profiling via mass spectrometry. Conclusions Our findings suggest that intestine and liver react to a high dietary fat intake by an activation of de novo cholesterol synthesis and other cholesterol-saving mechanisms, as well as with major changes in phospholipid metabolism, to accommodate to the fat load.

  10. 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 ...

  11. 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

  12. Cholesterol, the central lipid of mammalian cells

    NARCIS (Netherlands)

    Maxfield, F. R.; van Meer, G.

    2010-01-01

    Despite its importance for mammalian cell biology and human health, there are many basic aspects of cholesterol homeostasis that are not well understood. Even for the well-characterized delivery of cholesterol to cells via lipoproteins, a novel regulatory mechanism has been discovered recently, invo

  13. Prosopis farcta beans increase HDL cholesterol and decrease LDL cholesterol in ostriches (Struthio camelus).

    Science.gov (United States)

    Omidi, Arash; Ansari nik, Hossein; Ghazaghi, Mahmood

    2013-02-01

    Ten blue-neck male ostriches (Struthio camelus) were fed Prosopis farcta beans throughout a 30-day experiment. Blood samples were collected from ostriches on days 0 and 30 to measure levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, total serum protein, albumin, globulin, cholesterol, calcium, inorganic phosphorus, the activity of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase (γ-GT). From days 0 to 30, HDL cholesterol, total protein, and globulins levels increased significantly whereas LDL cholesterol, inorganic phosphorus, and γ-GT activity decreased significantly.

  14. 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...

  15. 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...

  16. 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...

  17. Huntington's disease: effect of cysteamine, a somatostatin-depleting agent.

    Science.gov (United States)

    Shults, C; Steardo, L; Barone, P; Mohr, E; Juncos, J; Serrati, C; Fedio, P; Tamminga, C A; Chase, T N

    1986-08-01

    Somatostatin levels in the basal ganglia are elevated in Huntington's disease. A controlled therapeutic trial of the somatostatin-depleting agent, cysteamine, was therefore conducted in five patients, including one with the rigid-akinetic form. Maximum tolerated dosage for 2 weeks produced no consistent change in extrapyramidal or dementia scores. Somatostatin concentrations were not significantly altered in plasma or CSF. Growth hormone levels, on the other hand, more than doubled, suggesting a functionally significant decrease in central somatostatin levels. PMID:2874527

  18. The role of cholesterol in the association of endoplasmic reticulum membranes with mitochondria

    International Nuclear Information System (INIS)

    Highlights: ► The endoplasmic reticulum subdomain termed MAM associates with mitochondria. ► The biophysical role of lipids in the MAM–mitochondria association is unknown. ► The in vitro membrane association assay was used to examine the role of lipids. ► Cholesterol was found to negatively regulate the association. -- Abstract: The unique endoplasmic reticulum (ER) subdomain termed the mitochondria-associated ER membrane (MAM) engages the physical connection between the ER and the mitochondrial outer membrane and plays a role in regulating IP3 receptor-mediated Ca2+ influx and the phospholipid transport between the two organelles. The MAM contains certain signaling and membrane-tethering proteins but also lipids including cholesterol. The biophysical role of lipids at the MAM, specifically in the physical interaction between the MAM of the ER and mitochondria, remains not totally clarified. Here we employed the in vitro membrane association assay to investigate the role of cholesterol in the association between MAMs and mitochondria. The purified MAMs and mitochondria were mixed in vitro in a test tube and then the physical association of the two subcellular organelles was quantified indirectly by measuring the presence of the MAM-specific protein sigma-1 receptors in the mitochondria fraction. Purified MAMs contained free cholesterol approximately 7 times higher than that in microsomes. We found that depletion of cholesterol in MAMs with methyl-β-cyclodextrin (MβC) significantly increases the association between MAMs and mitochondria, whereas MβC saturated with cholesterol does not change the association. 14C-Serine pulse-labeling demonstrated that the treatment of living cells with MβC decreases the level of de novo synthesized 14C-phosphatidylserine (PtSer) and concomitantly increases greatly the synthesis of 14C-phosphatidylethanolamine (PtEt). Apparently, cholesterol depletion increased the PtSer transport from MAMs to mitochondria. Our findings

  19. The role of cholesterol in the association of endoplasmic reticulum membranes with mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, Michiko [Cellular Stress Signaling Unit, Integrative Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224 (United States); Hayashi, Teruo, E-mail: thayashi@mail.nih.gov [Cellular Stress Signaling Unit, Integrative Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224 (United States); Su, Tsung-Ping, E-mail: tsu@intra.nida.nih.gov [Cellular Pathobiology Section, Integrative Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224 (United States)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer The endoplasmic reticulum subdomain termed MAM associates with mitochondria. Black-Right-Pointing-Pointer The biophysical role of lipids in the MAM-mitochondria association is unknown. Black-Right-Pointing-Pointer The in vitro membrane association assay was used to examine the role of lipids. Black-Right-Pointing-Pointer Cholesterol was found to negatively regulate the association. -- Abstract: The unique endoplasmic reticulum (ER) subdomain termed the mitochondria-associated ER membrane (MAM) engages the physical connection between the ER and the mitochondrial outer membrane and plays a role in regulating IP{sub 3} receptor-mediated Ca{sup 2+} influx and the phospholipid transport between the two organelles. The MAM contains certain signaling and membrane-tethering proteins but also lipids including cholesterol. The biophysical role of lipids at the MAM, specifically in the physical interaction between the MAM of the ER and mitochondria, remains not totally clarified. Here we employed the in vitro membrane association assay to investigate the role of cholesterol in the association between MAMs and mitochondria. The purified MAMs and mitochondria were mixed in vitro in a test tube and then the physical association of the two subcellular organelles was quantified indirectly by measuring the presence of the MAM-specific protein sigma-1 receptors in the mitochondria fraction. Purified MAMs contained free cholesterol approximately 7 times higher than that in microsomes. We found that depletion of cholesterol in MAMs with methyl-{beta}-cyclodextrin (M{beta}C) significantly increases the association between MAMs and mitochondria, whereas M{beta}C saturated with cholesterol does not change the association. {sup 14}C-Serine pulse-labeling demonstrated that the treatment of living cells with M{beta}C decreases the level of de novo synthesized {sup 14}C-phosphatidylserine (PtSer) and concomitantly increases greatly the synthesis of

  20. Membrane cholesterol regulates lysosome-plasma membrane fusion events and modulates Trypanosoma cruzi invasion of host cells.

    Directory of Open Access Journals (Sweden)

    Bárbara Hissa

    Full Text Available BACKGROUND: Trypomastigotes of Trypanosoma cruzi are able to invade several types of non-phagocytic cells through a lysosomal dependent mechanism. It has been shown that, during invasion, parasites trigger host cell lysosome exocytosis, which initially occurs at the parasite-host contact site. Acid sphingomyelinase released from lysosomes then induces endocytosis and parasite internalization. Lysosomes continue to fuse with the newly formed parasitophorous vacuole until the parasite is completely enclosed by lysosomal membrane, a process indispensable for a stable infection. Previous work has shown that host membrane cholesterol is also important for the T. cruzi invasion process in both professional (macrophages and non-professional (epithelial phagocytic cells. However, the mechanism by which cholesterol-enriched microdomains participate in this process has remained unclear. METHODOLOGY/PRINCIPAL FINDING: In the present work we show that cardiomyocytes treated with MβCD, a drug able to sequester cholesterol from cell membranes, leads to a 50% reduction in invasion by T. cruzi trypomastigotes, as well as a decrease in the number of recently internalized parasites co-localizing with lysosomal markers. Cholesterol depletion from host membranes was accompanied by a decrease in the labeling of host membrane lipid rafts, as well as excessive lysosome exocytic events during the earlier stages of treatment. Precocious lysosomal exocytosis in MβCD treated cells led to a change in lysosomal distribution, with a reduction in the number of these organelles at the cell periphery, and probably compromises the intracellular pool of lysosomes necessary for T. cruzi invasion. CONCLUSION/SIGNIFICANCE: Based on these results, we propose that cholesterol depletion leads to unregulated exocytic events, reducing lysosome availability at the cell cortex and consequently compromise T. cruzi entry into host cells. The results also suggest that two different pools of

  1. 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

  2. Guar gum and similar soluble fibers in the regulation of cholesterol metabolism: Current understandings and future research priorities

    Directory of Open Access Journals (Sweden)

    Todd C Rideout

    2008-10-01

    Full Text Available Todd C Rideout1, Scott V Harding1, Peter JH Jones1, Ming Z Fan21Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada; 2Centre for Nutrition Modeling, Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, CanadaAbstract: The hypocholesterolemic effects associated with soluble fiber consumption are clear from animal model and human clinical investigations. Moreover, the modulation of whole-body cholesterol metabolism in response to dietary fiber consumption, including intestinal cholesterol absorption and fecal sterol and bile acid loss, has been the subject of many published reports. However, our understanding of how dietary fibers regulate molecular events at the gene/protein level and alter cellular cholesterol metabolism is limited. The modern emphasis on molecular nutrition and rapid progress in ‘high-dimensional’ biological techniques will permit further explorations of the role of genetic polymorphisms in determining the variable interindividual responses to soluble fibers. Furthermore, with traditional molecular biology tools and the application of ‘omic’ technology, specific insight into how fibers modulate the expression of genes and proteins that regulate intestinal cholesterol absorption and alter hepatic sterol balance will be gained. Detailed knowledge of the molecular mechanisms by which soluble fibers reduce plasma cholesterol concentrations is paramount to developing novel fiber-based “cocktails” that target specific metabolic pathways to gain maximal cholesterol reductions.Keywords: dietary fiber, cholesterol, bile acids, gene, protein

  3. Guar gum and similar soluble fibers in the regulation of cholesterol metabolism: Current understandings and future research priorities

    Directory of Open Access Journals (Sweden)

    Todd C Rideout

    2008-08-01

    Full Text Available Todd C Rideout1, Scott V Harding1, Peter JH Jones1, Ming Z Fan21Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada; 2Centre for Nutrition Modeling, Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, CanadaAbstract: The hypocholesterolemic effects associated with soluble fiber consumption are clear from animal model and human clinical investigations. Moreover, the modulation of whole-body cholesterol metabolism in response to dietary fiber consumption, including intestinal cholesterol absorption and fecal sterol and bile acid loss, has been the subject of many published reports. However, our understanding of how dietary fibers regulate molecular events at the gene/protein level and alter cellular cholesterol metabolism is limited. The modern emphasis on molecular nutrition and rapid progress in ‘high-dimensional’ biological techniques will permit further explorations of the role of genetic polymorphisms in determining the variable interindividual responses to soluble fibers. Furthermore, with traditional molecular biology tools and the application of ‘omic’ technology, specific insight into how fibers modulate the expression of genes and proteins that regulate intestinal cholesterol absorption and alter hepatic sterol balance will be gained. Detailed knowledge of the molecular mechanisms by which soluble fibers reduce plasma cholesterol concentrations is paramount to developing novel fiber-based “cocktails” that target specific metabolic pathways to gain maximal cholesterol reductions.Keywords: dietary fiber, cholesterol, bile acids, gene, protein

  4. 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

  5. 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 ...

  6. 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 ...

  7. Incorporation of cholesterol into the cellular membrane of Lactobacillus acidophilus ATCC 43121

    International Nuclear Information System (INIS)

    Cholesterol that was assimilated by Lactobacillus acidophilus ATCC 43121 was not metabolically degraded; most of it was recovered with the cells. Cells that were grown in the presence of cholesterol micelles and bile salts were more resistant to lysis by sonication than were those grown in their absence, suggesting a possible alteration of the cell wall or membrane. Cholesterol assimilation occurred during growth at pH 6.0 as well as during growth without pH control. Part of the cholesterol that was assimilated by cells was recovered in the membrane fractions of cells grown under both conditions. There was no difference in the amount taken up from cholesterol micelles that were prepared using dioleoyl L-alpha-phosphatidylcholine or distearoyl L-alpha-phosphatidylcholine. Thus, the type of fatty acid (unsaturated or saturated) in the phospholipid did not influence the assimilation. As the amount of Tween 80 in the growth media increased beyond 0.05%, cholesterol uptake decreased, and the amount of growth remained the same. The higher concentrations of Tween 80 may have adversely affected the permeability of the cells

  8. Effect of gamma radiation and storage on cholesterol oxidative stability of raw and processed eggs

    International Nuclear Information System (INIS)

    The egg have being studied due its nutritional wealth, for show industrial interest as a raw material, e due its higher cholesterol content. At the same time, due its susceptibility to contamination mainly with salmonella, it is being proposed the ionizing radiation as a hygienic measure. Cholesterol is subject to oxidation, that it is facilitated by several factors, among them ionizing radiation. Formed cholesterol oxides, by its turn, show harmful biological properties to human health, as atherogenicity, cytotoxicity, carcinogenicity and mutagenicity, among others. The objectives of this work were evaluate the effect of ionizing radiation over pH, viscosity and color, besides the oxidative stability of cholesterol, in stored and processed crude eggs. With the increase of used doses (1, 2 and 3 KGy), there was an reduction in the viscosity of the egg white and in the color yolk egg, besides the increase in lipidic oxidation, measured through tiobarbituric acid-reactive substances (TBARS). Specifications as humidity, total lipids and egg yolk cholesterol were not influenced. In the subject of humidity and of cholesterol, there was an meaningful alteration due storage (30 days in 4 deg C). The sum of the analyzed oxides didn't variate with the irradiation, only individually, although it did vary with storage. The thermal processing caused an meaningful increase of TBARS, but despite this, the oxides sum didn't differed between treatments. (author)

  9. 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

  10. Depleted uranium: Metabolic disruptor?; Uranium appauvri: perturbateur metabolique?

    Energy Technology Data Exchange (ETDEWEB)

    Souidi, Maamar; Dublineau, Isabelle; Lestaevel, Philippe [Institut de Radioprotection et de Surete Nucleaire - IRSN, Direction de la radioprotection de l' homme, Laboratoire de radiotoxicologie experimentale, Service de radiobiologie et d' epidemiologie, BP 17, 92262 Fontenay-aux-Roses cedex (France)

    2011-11-15

    The presence of uranium in the environment can lead to long-term contamination of the food chain and of water intended for human consumption and thus raises many questions about the scientific and societal consequences of this exposure on population health. Although the biological effects of chronic low-level exposure are poorly understood, results of various recent studies show that contamination by depleted uranium (DU) induces subtle but significant biological effects at the molecular level in organs including the brain, liver, kidneys and testicles. For the first time, it has been demonstrated that DU induces effects on several metabolic pathways, including those metabolizing vitamin D, cholesterol, steroid hormones, acetylcholine and xenobiotics. This evidence strongly suggests that DU might well interfere with many metabolic pathways. It might thus contribute, together with other man-made substances in the environment, to increased health risks in some regions. (authors)

  11. Beneficial effect of low dose Amlodipine vs Nifedipine on serum cholesterol profile of rabbits receiving standard diet.

    Directory of Open Access Journals (Sweden)

    Bavane DS, Rajesh CS, Gurudatta Moharir, Bharatha Ambadasu

    2013-01-01

    Full Text Available To investigate the effect of low dose amlodipine v/s nifedipine on serum cholesterol profile of rabbits receiving standard diet. Methods: Fourty Newzealand rabbits were selected for the study. Their cholesterol profile was estimated at the beginning of the study. Rabbits were grouped into 4 groups receiving standard diet (control group, standard diet + vehicle propylene glycol, standard diet + nifedipine dissolved in propylene glycol and standard diet + amlodipine dissolved in propylene glycol. Along with standard diet they were treated with respective drugs for ten weeks. At the end of ten weeks serum cholesterol profile was estimated. Results: The cholesterol profile was estimated at the beginning and at the end of ten weeks. Total cholesterol in the amlodipine group decreased from 97±4.06 mg/dl to 90±4.2 mg/dl and HDL-Cholesterol increased from 32.01±4.40 mg/dl to 37±4.60 mg/dl after 10 week treatment but these changes were not significant. LDL cholesterol decreased significantly in rabbits with low dose of amlodipine from 55.42±3.32 mg/dl to 32.40±3.22 mg/dl and. In the nifedipine group there was a slight increase in total cholesterol from 102.49±5.16 mg/dl to 106±5.39 mg/dl, HDL cholesterol from 34.10±2.80 to 35.16±2.82 mg/dl and LDL cholesterol also increased from 56.20±2.20 mg/dl to 59.00±2.20 mg/dl after 10 week treatment. Conclusion: The study shows amlodipine produces favorable alterations in serum cholesterol profile

  12. Ozone Depletion from Nearby Supernovae

    CERN Document Server

    Gehrels, N; Jackman, C H; Cannizzo, J K; Mattson, B J; Chen, W; Gehrels, Neil; Laird, Claude M.; Jackman, Charles H.; Cannizzo, John K.; Mattson, Barbara J.; Chen, Wan

    2003-01-01

    Estimates made in the 1970's indicated that a supernova occurring within tens of parsecs of Earth could have significant effects on the ozone layer. Since that time, improved tools for detailed modeling of atmospheric chemistry have been developed to calculate ozone depletion, and advances have been made in theoretical modeling of supernovae and of the resultant gamma-ray spectra. In addition, one now has better knowledge of the occurrence rate of supernovae in the galaxy, and of the spatial distribution of progenitors to core-collapse supernovae. We report here the results of two-dimensional atmospheric model calculations that take as input the spectral energy distribution of a supernova, adopting various distances from Earth and various latitude impact angles. In separate simulations we calculate the ozone depletion due to both gamma-rays and cosmic rays. We find that for the combined ozone depletion roughly to double the ``biologically active'' UV flux received at the surface of the Earth, the supernova mu...

  13. Ozone Depletion from Nearby Supernovae

    Science.gov (United States)

    Gehrels, Neil; Laird, Claude M.; Jackman, Charles H.; Cannizzo, John K.; Mattson, Barbara J.; Chen, Wan; Bhartia, P. K. (Technical Monitor)

    2002-01-01

    Estimates made in the 1970's indicated that a supernova occurring within tens of parsecs of Earth could have significant effects on the ozone layer. Since that time improved tools for detailed modeling of atmospheric chemistry have been developed to calculate ozone depletion, and advances have been made also in theoretical modeling of supernovae and of the resultant gamma ray spectra. In addition, one now has better knowledge of the occurrence rate of supernovae in the galaxy, and of the spatial distribution of progenitors to core-collapse supernovae. We report here the results of two-dimensional atmospheric model calculations that take as input the spectral energy distribution of a supernova, adopting various distances from Earth and various latitude impact angles. In separate simulations we calculate the ozone depletion due to both gamma rays and cosmic rays. We find that for the combined ozone depletion from these effects roughly to double the 'biologically active' UV flux received at the surface of the Earth, the supernova must occur at approximately or less than 8 parsecs.

  14. HD depletion in starless cores

    CERN Document Server

    Sipilä, O; Harju, J

    2013-01-01

    Aims: We aim to investigate the abundances of light deuterium-bearing species such as HD, H2D+ and D2H+ in a gas-grain chemical model including an extensive description of deuterium and spin state chemistry, in physical conditions appropriate to the very centers of starless cores. Methods: We combine a gas-grain chemical model with radiative transfer calculations to simulate density and temperature structure in starless cores. The chemical model includes deuterated forms of species with up to 4 atoms and the spin states of the light species H2, H2+ and H3+ and their deuterated forms. Results: We find that HD eventually depletes from the gas phase because deuterium is efficiently incorporated to grain-surface HDO, resulting in inefficient HD production on grains. HD depletion has consequences not only on the abundances of e.g. H2D+ and D2H+, whose production depends on the abundance of HD, but also on the spin state abundance ratios of the various light species, when compared with the complete depletion model ...

  15. Physiological and pathological implications of cholesterol.

    Science.gov (United States)

    Cortes, Victor A; Busso, Dolores; Maiz, Alberto; Arteaga, Antonio; Nervi, Flavio; Rigotti, Attilio

    2014-01-01

    Cholesterol has evolved to fulfill sophisticated biophysical, cell signaling and endocrine requirements of animal systems. At a cellular level, cholesterol is found in membranes, where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signaling functions. At an organismal level, cholesterol is the precursor for all steroid hormones, including gluco- and mineralo-corticoids, sex hormones and vitamin D, all of which regulate carbohydrate, sodium, reproductive and bone homeostasis, respectively. This sterol is also the precursor for bile acids, which are important for intestinal absorption of dietary lipids as well as energy and glucose metabolic regulation. Importantly, complex mechanisms maintain cholesterol within physiological ranges and the disregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these diseases has been demonstrated by diverse genetic and pharmacologic animal models that are commented in this review. PMID:24389193

  16. 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.

  17. 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.

  18. 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

  19. Accumulation of Cholesterol Esters in ex vivo Lymphocytes from Scrapie-susceptible Sheep and in Scrapie-infected Mouse Neuroblastoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Alessandra Pani

    2007-01-01

    Full Text Available Our studies on the role of cholesterol homeostasis in the pathogenesis of scrapie in sheep, revealed abnormal accumulation of cholesterol esters in brains and in ex vivo skin fibroblasts from genetically scrapie-susceptible, as compared to sheep with resistant genotype. We now report that PBMCs isolated from scrapie-susceptible sheep, as well as mouse neuroblastoma cell lines persistently infected with two different mouse-adapted strains of scrapie, showed similar alterations with up to 3-fold higher cholesterol ester levels than their resistant or uninfected counterparts. Treatments with drugs that interfere with intracellular cholesterol metabolism strongly reduced accumulation of cholesterol esters in scrapie-infected cell lines, whereas had significantly lower, or no effect, in uninfected cell line. These data add support to our hypothesis that accumulation of cholesterol esters may represent a biological marker of susceptibility to prion infection and a potential molecular target for prion inhibitors.

  20. Cholesterol binding by the bacterial type III translocon is essential for virulence effector delivery into mammalian cells.

    Science.gov (United States)

    Hayward, Richard D; Cain, Robert J; McGhie, Emma J; Phillips, Neil; Garner, Matthew J; Koronakis, Vassilis

    2005-05-01

    A ubiquitous early step in infection of man and animals by enteric bacterial pathogens like Salmonella, Shigella and enteropathogenic Escherichia coli (EPEC) is the translocation of virulence effector proteins into mammalian cells via specialized type III secretion systems (TTSSs). Translocated effectors subvert the host cytoskeleton and stimulate signalling to promote bacterial internalization or survival. Target cell plasma membrane cholesterol is central to pathogen-host cross-talk, but the precise nature of its critical contribution remains unknown. Using in vitro cholesterol-binding assays, we demonstrate that Salmonella (SipB) and Shigella (IpaB) TTSS translocon components bind cholesterol with high affinity. Direct visualization of cell-associated fluorescently labelled SipB and parallel immunogold transmission electron microscopy revealed that cholesterol levels limit both the amount and distribution of plasma membrane-integrated translocon. Correspondingly, cholesterol depletion blocked effector translocation into cultured mammalian cells by not only the related Salmonella and Shigella TTSSs, but also the more divergent EPEC system. The data reveal that cholesterol-dependent association of the bacterial TTSS translocon with the target cell plasma membrane is essential for translocon activation and effector delivery into mammalian cells.

  1. The Case of Ozone Depletion

    Science.gov (United States)

    Lambright, W. Henry

    2005-01-01

    While the National Aeronautics and Space Administration (NASA) is widely perceived as a space agency, since its inception NASA has had a mission dedicated to the home planet. Initially, this mission involved using space to better observe and predict weather and to enable worldwide communication. Meteorological and communication satellites showed the value of space for earthly endeavors in the 1960s. In 1972, NASA launched Landsat, and the era of earth-resource monitoring began. At the same time, in the late 1960s and early 1970s, the environmental movement swept throughout the United States and most industrialized countries. The first Earth Day event took place in 1970, and the government generally began to pay much more attention to issues of environmental quality. Mitigating pollution became an overriding objective for many agencies. NASA's existing mission to observe planet Earth was augmented in these years and directed more toward environmental quality. In the 1980s, NASA sought to plan and establish a new environmental effort that eventuated in the 1990s with the Earth Observing System (EOS). The Agency was able to make its initial mark via atmospheric monitoring, specifically ozone depletion. An important policy stimulus in many respects, ozone depletion spawned the Montreal Protocol of 1987 (the most significant international environmental treaty then in existence). It also was an issue critical to NASA's history that served as a bridge linking NASA's weather and land-resource satellites to NASA s concern for the global changes affecting the home planet. Significantly, as a global environmental problem, ozone depletion underscored the importance of NASA's ability to observe Earth from space. Moreover, the NASA management team's ability to apply large-scale research efforts and mobilize the talents of other agencies and the private sector illuminated its role as a lead agency capable of crossing organizational boundaries as well as the science-policy divide.

  2. 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 ...

  3. 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 ...

  4. 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

  5. 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...

  6. 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...

  7. Assessing possible hazards of reducing serum cholesterol.

    OpenAIRE

    Law, M. R.; Thompson, S. G.; Wald, N J

    1994-01-01

    OBJECTIVE--To assess whether low serum cholesterol concentration increases mortality from any cause. DESIGN--Systematic review of published data on mortality from causes other than ischaemic heart disease derived from the 10 largest cohort studies, two international studies, and 28 randomised trials, supplemented by unpublished data on causes of death obtained when necessary. MAIN OUTCOME MEASURES--Excess cause specific mortality associated with low or lowered serum cholesterol concentration....

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjaer; Hougaard, Charlotte; Hoffmann, Else K;

    2006-01-01

    ) analogue or a PtdIns(4,5)P(2)-blocking antibody in the pipette, or neomycin treatment to sequester PtdIns(4,5)P(2). It is suggested that in ELA cells, F-actin and Rho-Rho kinase modulate VRAC magnitude and activation rate, respectively, and that cholesterol depletion potentiates VRAC at least in part...

  13. "When the going gets tough, who keeps going?" : Depletion sensitivity moderates the ego-depletion effect

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In thre

  14. Cellular Cholesterol Distribution Influences Proteolytic Release of the LRP-1 Ectodomain

    Science.gov (United States)

    Dekky, Bassil; Wahart, Amandine; Sartelet, Hervé; Féré, Michaël; Angiboust, Jean-François; Dedieu, Stéphane; Piot, Olivier; Devy, Jérôme; Emonard, Hervé

    2016-01-01

    Low-density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional matricellular receptor composed of a large ligand-binding subunit (515-kDa α-chain) associated with a short trans-membrane subunit (85-kDa β-chain). LRP-1, which exhibits both endocytosis and cell signaling properties, plays a key role in tumor invasion by regulating the activity of proteinases such as matrix metalloproteinases (MMPs). LRP-1 is shed at the cell surface by proteinases such as membrane-type 1 MMP (MT1-MMP) and a disintegrin and metalloproteinase-12 (ADAM-12). Here, we show by using biophysical, biochemical, and cellular imaging approaches that efficient extraction of cell cholesterol and increased LRP-1 shedding occur in MDA-MB-231 breast cancer cells but not in MDA-MB-435 cells. Our data show that cholesterol is differently distributed in both cell lines; predominantly intracellularly for MDA-MB-231 cells and at the plasma membrane for MDA-MB-435 cells. This study highlights the relationship between the rate and cellular distribution of cholesterol and its impact on LRP-1 shedding modulation. Altogether, our data strongly suggest that the increase of LRP-1 shedding upon cholesterol depletion induces a higher accessibility of the sheddase substrate, i.e., LRP-1, at the cell surface rather than an increase of expression of the enzyme. PMID:26903870

  15. De novo cholesterol synthesis at the crossroads of adaptive response to extracellular stress through SREBP.

    Science.gov (United States)

    Robichon, Céline; Dugail, Isabelle

    2007-02-01

    Cell sterol supply is subjected to tight negative feedback regulation through the SREBP pathway. Upon cholesterol depletion, SREBP transcription factors become activated by cleavage of a membrane bound precursor form, which stimulates the expression of the genes encoding proteins of the cholesterol synthesis pathway. In this paper, we discuss two situations of extracellular stress (hypoxia and heat shock) in which the cholesterol synthesis pathway and SREBPs are directly impacted to generate an adaptive response to cell damage. On one hand, the lack of oxygen in fission yeast Saccharomyces pombe induces a drop in cholesterol synthesis which in turn activates SREBP-mediated transcription. The presence of genes involved in the anaerobic growth program among SREBP target genes in fission yeast, indicates that SREBP behaves as an oxygen sensor, required for adaptive growth in low oxygen. On the other hand, upon heat shock in mammalian cells, SREBP-responsive heat shock proteins have been characterized, which were able to upregulate sterol synthesis by targeting the activity of HMG-CoA reductase, the rate limiting enzyme in this pathway. Although not yet proven, high rates of sterol synthesis can be viewed as an adaptive response to correct structural membrane damage and bilayer fluidification induced by thermal stress. Together these situations illustrate how the highly regulated SREBP pathway for the control of sterol synthesis can be used to achieve cell adaptive responses to extracellular stresses.

  16. Effects of platelet depletion on the unanesthetized sheep's pulmonary response to endotoxemia.

    OpenAIRE

    Snapper, J R; Hinson, J M; Hutchison, A A; Lefferts, P L; Ogletree, M L; Brigham, K L

    1984-01-01

    The effect of platelet depletion on the unanesthetized sheep's pulmonary response to endotoxemia was studied in eight unanesthetized sheep. Platelets were depleted with rabbit anti-sheep platelet antibodies (APA). Bolus injections of APA alone caused marked pulmonary hypertension (PPA increased from 21 +/- 2 to 62 +/- 5 cm H2O +/- SE) and alterations in lung mechanics (dynamic compliance of the lung [Cdyn] decreased to 38.5 +/- 4.6% and resistance to air flow across the lung [RL] increased to...

  17. The 1988 Antarctic ozone depletion - Comparison with previous year depletions

    Science.gov (United States)

    Schoeberl, Mark R.; Stolarski, Richard S.; Krueger, Arlin J.

    1989-01-01

    The 1988 spring Antarctic ozone depletion was observed by TOMS to be substantially smaller than in recent years. The minimum polar total ozone values declined only 15 percent during September 1988, compared to nearly 50 percent during September 1987. At southern midlatitudes, exceptionally high total ozone values were recorded beginning in July 1988. The total integrated southern hemispheric ozone increased rapidly during the Austral spring, approaching 1980 levels during October. The high midlatitude total ozone values were associated with a substantial increase in eddy activity as indicated by the standard deviation in total ozone in the zonal band 30-60 deg S. Mechanisms through which the increased midlatitude eddy activity could disrupt the formation of the Antarctic ozone hole are briefly discussed.

  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. 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

  20. 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.

  1. 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 ...

  2. Cholesterol and F-actin are required for clustering of recycling synaptic vesicle proteins in the presynaptic plasma membrane.

    Science.gov (United States)

    Dason, Jeffrey S; Smith, Alex J; Marin, Leo; Charlton, Milton P

    2014-02-15

    Synaptic vesicles (SVs) and their proteins must be recycled for sustained synaptic transmission. We tested the hypothesis that SV cholesterol is required for proper sorting of SV proteins during recycling in live presynaptic terminals. We used the reversible block of endocytosis in the Drosophila temperature-sensitive dynamin mutant shibire-ts1 to trap exocytosed SV proteins, and then examined the effect of experimental treatments on the distribution of these proteins within the presynaptic plasma membrane by confocal microscopy. SV proteins synaptotagmin, vglut and csp were clustered following SV trapping in control experiments but dispersed in samples treated with the cholesterol chelator methyl-β-cyclodextrin to extract SV cholesterol. There was accumulation of phosphatidylinositol (4,5)-bisphosphate (PIP2) in presynaptic terminals following SV trapping and this was reduced following SV cholesterol extraction. Reduced PIP2 accumulation was associated with disrupted accumulation of actin in presynaptic terminals. Similar to vesicular cholesterol extraction, disruption of actin by latrunculin A after SV proteins had been trapped on the plasma membrane resulted in the dispersal of SV proteins and prevented recovery of synaptic transmission due to impaired endocytosis following relief of the endocytic block. Our results demonstrate that vesicular cholesterol is required for aggregation of exocytosed SV proteins in the presynaptic plasma membrane and are consistent with a mechanism involving regulation of PIP2 accumulation and local actin polymerization by cholesterol. Thus, alteration of membrane or SV lipids may affect the ability of synapses to undergo sustained synaptic transmission by compromising the recycling of SV proteins.

  3. Depleted uranium disposal options evaluation

    International Nuclear Information System (INIS)

    The Department of Energy (DOE), Office of Environmental Restoration and Waste Management, has chartered a study to evaluate alternative management strategies for depleted uranium (DU) currently stored throughout the DOE complex. Historically, DU has been maintained as a strategic resource because of uses for DU metal and potential uses for further enrichment or for uranium oxide as breeder reactor blanket fuel. This study has focused on evaluating the disposal options for DU if it were considered a waste. This report is in no way declaring these DU reserves a ''waste,'' but is intended to provide baseline data for comparison with other management options for use of DU. To PICS considered in this report include: Retrievable disposal; permanent disposal; health hazards; radiation toxicity and chemical toxicity

  4. Depleted Argon from Underground Sources

    International Nuclear Information System (INIS)

    Argon is a strong scintillator and an ideal target for Dark Matter detection; however 39Ar contamination in atmospheric argon from cosmic ray interactions limits the size of liquid argon dark matter detectors due to pile-up. Argon from deep underground is depleted in 39Ar due to the cosmic ray shielding of the earth. In Cortez, Colorado, a CO2 well has been discovered to contain approximately 600 ppm of argon as a contamination in the CO2. We first concentrate the argon locally to 3% in an Ar, N2, and He mixture, from the CO2 through chromatographic gas separation, and then the N2 and He will be removed by continuous distillation to purify the argon. We have collected 26 kg of argon from the CO2 facility and a cryogenic distillation column is under construction at Fermilab to further purify the argon.

  5. Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma.

    Science.gov (United States)

    Guillaumond, Fabienne; Bidaut, Ghislain; Ouaissi, Mehdi; Servais, Stéphane; Gouirand, Victoire; Olivares, Orianne; Lac, Sophie; Borge, Laurence; Roques, Julie; Gayet, Odile; Pinault, Michelle; Guimaraes, Cyrille; Nigri, Jérémy; Loncle, Céline; Lavaut, Marie-Noëlle; Garcia, Stéphane; Tailleux, Anne; Staels, Bart; Calvo, Ezequiel; Tomasini, Richard; Iovanna, Juan Lucio; Vasseur, Sophie

    2015-02-24

    The malignant progression of pancreatic ductal adenocarcinoma (PDAC) is accompanied by a profound desmoplasia, which forces proliferating tumor cells to metabolically adapt to this new microenvironment. We established the PDAC metabolic signature to highlight the main activated tumor metabolic pathways. Comparative transcriptomic analysis identified lipid-related metabolic pathways as being the most highly enriched in PDAC, compared with a normal pancreas. Our study revealed that lipoprotein metabolic processes, in particular cholesterol uptake, are drastically activated in the tumor. This process results in an increase in the amount of cholesterol and an overexpression of the low-density lipoprotein receptor (LDLR) in pancreatic tumor cells. These findings identify LDLR as a novel metabolic target to limit PDAC progression. Here, we demonstrate that shRNA silencing of LDLR, in pancreatic tumor cells, profoundly reduces uptake of cholesterol and alters its distribution, decreases tumor cell proliferation, and limits activation of ERK1/2 survival pathway. Moreover, blocking cholesterol uptake sensitizes cells to chemotherapeutic drugs and potentiates the effect of chemotherapy on PDAC regression. Clinically, high PDAC Ldlr expression is not restricted to a specific tumor stage but is correlated to a higher risk of disease recurrence. This study provides a precise overview of lipid metabolic pathways that are disturbed in PDAC. We also highlight the high dependence of pancreatic cancer cells upon cholesterol uptake, and identify LDLR as a promising metabolic target for combined therapy, to limit PDAC progression and disease patient relapse. PMID:25675507

  6. Transcriptome profiling unveils the role of cholesterol in IL-17A signaling in psoriasis.

    Science.gov (United States)

    Varshney, Pallavi; Narasimhan, Aarti; Mittal, Shankila; Malik, Garima; Sardana, Kabir; Saini, Neeru

    2016-01-01

    Psoriasis is a chronic inflammatory skin disease characterized by altered proliferation and differentiation of keratinocytes as well as infiltration of immune cells. Increased expression of Th17 cells and cytokines secreted by them provides evidence for its central role in the pathogenesis of psoriasis. IL-17A, signature cytokine of Th17 cells was found to be highly differentially expressed in psoriatic lesional skin. However, cellular and molecular mechanism by which IL-17A exerts its function on keratinocyte is incompletely understood. To understand IL-17A mediated signal transduction pathways, gene expression profiling was done and differentially expressed genes were analysed by IPA software. Here, we demonstrate that during IL-17A signaling total cholesterol levels were elevated, which in turn resulted in the suppression of genes of cholesterol and fatty acid biosynthesis. We found that accumulation of cholesterol was essential for IL-17A signaling as reduced total cholesterol levels by methyl β cyclodextrin (MBCD), significantly decreased IL-17A induced secretion of CCL20, IL-8 and S100A7 from the keratinocytes. To our knowledge this study for the first time unveils that high level of intracellular cholesterol plays a crucial role in IL-17A signaling in keratinocytes and may explain the strong association between psoriasis and dyslipidemia. PMID:26781963

  7. Polyunsaturated fatty acyl-coenzyme As are inhibitors of cholesterol biosynthesis in zebrafish and mice

    Directory of Open Access Journals (Sweden)

    Santhosh Karanth

    2013-11-01

    Lipid disorders pose therapeutic challenges. Previously we discovered that mutation of the hepatocyte β-hydroxybutyrate transporter Slc16a6a in zebrafish causes hepatic steatosis during fasting, marked by increased hepatic triacylglycerol, but not cholesterol. This selective diversion of trapped ketogenic carbon atoms is surprising because acetate and acetoacetate can exit mitochondria and can be incorporated into both fatty acids and cholesterol in normal hepatocytes. To elucidate the mechanism of this selective diversion of carbon atoms to fatty acids, we fed wild-type and slc16a6a mutant animals high-protein ketogenic diets. We find that slc16a6a mutants have decreased activity of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr, despite increased Hmgcr protein abundance and relative incorporation of mevalonate into cholesterol. These observations suggest the presence of an endogenous Hmgcr inhibitor. We took a candidate approach to identify such inhibitors. First, we found that mutant livers accumulate multiple polyunsaturated fatty acids (PUFAs and PUFA-CoAs, and we showed that human HMGCR is inhibited by PUFA-CoAs in vitro. Second, we injected mice with an ethyl ester of the PUFA eicosapentaenoic acid and observed an acute decrease in hepatic Hmgcr activity, without alteration in Hmgcr protein abundance. These results elucidate a mechanism for PUFA-mediated cholesterol lowering through direct inhibition of Hmgcr.

  8. Changes during hibernation in different phospholipid and free and esterified cholesterol serum levels in black bears

    Science.gov (United States)

    Chauhan, V.; Sheikh, A.; Chauhan, A.; Tsiouris, J.; Malik, M.; Vaughan, M.

    2002-01-01

    During hibernation, fat is known to be the preferred source of energy. A detailed analysis of different phospholipids, as well as free and esterified cholesterol, was conducted to investigate lipid abnormalities during hibernation. The levels of total phospholipids and total cholesterol in the serum of black bears were found to increase significantly in hibernation as compared with the active state. Both free and esterified cholesterol were increased in the hibernating state in comparison with the active state (P catabolism of phospholipids and cholesterol is decreased during hibernation in black bears, leading to their increased levels in the hibernating state as compared with the active state. In summary, our results indicate that serum cholesterol and phospholipid fractions (except PE) are increased during hibernation in bears. It is proposed that the increase of these lipids may be due to the altered metabolism of lipoproteins that are responsible for the clearance of the lipids. ?? 2002 E??ditions scientifiques et me??dicales Elsevier SAS and Socie??te?? franc??aise de biochimie et biologie mole??culaire. All rights reserved.

  9. Effect of Melatonin and Cholesterol on the Structure of DOPC and DPPC Membranes

    Energy Technology Data Exchange (ETDEWEB)

    Drolle, E [University of Waterloo, Canada; Kucerka, Norbert [Canadian Neutron Beam Centre and Comelius University (Slovakia); Hoopes, M I [University of Waterloo, Canada; Choi, Y [University of Waterloo, Canada; Katsaras, John [ORNL; Karttunen, M [University of Waterloo, Canada; Leonenko, Z [University of Waterloo, Canada

    2013-01-01

    The cell membrane plays an important role in the molecular mechanism of amyloid toxicity associated with Alzheimer's disease. The membrane's chemical composition and the incorporation of small molecules, such as melatonin and cholesterol, can alter its structure and physical properties, thereby affecting its interaction with amyloid peptides. Both melatonin and cholesterol have been recently linked to amyloid toxicity. Melatonin has been shown to have a protective role against amyloid toxicity. However, the underlying molecular mechanism of this protection is still not well understood, and cholesterol's role remains controversial. We used small-angle neutron diffraction (SAND) from oriented lipid multi-layers, small-angle neutron scattering (SANS) from unilamellar vesicles experiments andMolecular Dynamics (MD) simulations to elucidate non-specific interactions of melatonin and cholesterol with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dipalmitoyl-snglycero-3-phosphocholine (DPPC) model membranes. We conclude that melatonin decreases the thickness of both model membranes by disordering the lipid hydrocarbon chains, thus increasing membrane fluidity. This result is in stark contrast to the much accepted ordering effect induced by cholesterol, which causes membranes to thicken.

  10. Effect of dimethylsulfoxide on sphingomyelinase activity and cholesterol metabolism in Niemann-Pick type C fibroblasts

    Directory of Open Access Journals (Sweden)

    Scalco F.B.

    1999-01-01

    Full Text Available 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. Sphingomyelinase activity was significantly increased in both groups of cells only when incubated with 2% DMSO (59.4 ± 9.1 and 77.0 ± 9.1 nmol h-1 mg protein-1, controls without and with 2% DMSO, respectively; 47.7 ± 5.2 and 55.8 ± 4.1 nmol h-1 mg protein-1, NPC without and with 2% DMSO, respectively. However, none of the DMSO concentrations used altered the amount of cholesterol in the cytoplasm of NPC cells (0.704 ± 0.049, 0.659 ± 0.041, 0.688 ± 0.063 and 0.733 ± 0.088 mg/mg protein, without DMSO, 1% DMSO, 2% DMSO and 4% DMSO, respectively. This finding suggests that sphingomyelinase deficiency is a secondary defect in NPC and shows that DMSO failed to remove the stored cholesterol. These data do not support the use of DMSO in the treatment of NPC patients.

  11. Vitamin D Supplementation Causes a Decrease in Blood Cholesterol in Professional Rowers.

    Science.gov (United States)

    Jastrzebski, Zbigniew; Kortas, Jakub; Kaczor, Katarzyna; Antosiewicz, Jedrzej

    2016-01-01

    In the skin vitamin D3 is synthesized from cholesterol, which leaves the question whether a feedback mechanism controlling the level of blood cholesterol exists. Here we investigate the effects of vitamin D3 supplementation on serum lipids in professional rowers. The rowers were divided into two groups following the same training schedule for 4 wk: one received placebo (TP) while the second received 5,000 IU of vitamin D3 every day (TD3). Plasma total antioxidant status, total triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL)-cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol (LDL-C) and 25-hydroxyvitamin D (25-OH-D3) were determined in pre- and post-intervention. The ratios of TC/HDL-C and LDL-C/HDL-C were also calculated. Furthermore, maximal oxygen uptake was also measured at baseline. There were significant decreases over time in the TD3 group in TC 186±18 vs 163±21 (pcaused a significant rise in blood 25-OH-D3 (+98%). Neither training nor vitamin D3 supplementation had an effect on total antioxidant status. In conclusion, the alterations in the lipoprotein profile seen in this study would suggest that effects of regular exercise on lipoprotein profile may linked to vitamin D3 status. PMID:27264092

  12. 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

  13. Depleted uranium. Nuclear related problems

    International Nuclear Information System (INIS)

    Depleted uranium (DU) has found a military application in Golf War, in Bosnia and in Yugoslavia (Kosovo). In military sense it was very efficient. But the fact that some parts of that ammunition are manufactured from depleted uranium, low level radioactive waste, implies other aspects of this application like radiological, ecological, jurist, ethical and psychological. The subject of this paper is just physical aspect. There are several problems concerning this aspect: production of DU, total amount of DU in the world, 235U/238U relation, radioactivity of DU, measurements, and presence of other radionuclides like plutonium. DU is by product of nuclear technology and represents low-level nuclear waste. Therefore it should be stored. Total amount of DU in the world is about one million tons with an annual increase of 30 000 t. The content of 235U in DU can vary in the range 0.16-0.3%. The total radioactivity of DU is a consequence of 7 radionuclides and amounts 39.42 Bq/mg. This include alpha, beta and gamma radioactivity. Because of characteristics of this radioactivity it is difficult to prospect the terrain except at the site of action. During the impact of DU rods four types of DU particles could be produced: whole penetrators, penetrator parts, big aerosols (>10 μm) and small aerosols (<10 μm). Most of these particles fall locally, although some of them could be find several tens of kilometers away. All these problems have been discussed in this paper. (author)

  14. 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.

  15. [Trans-intestinal cholesterol excretion (TICE): a new route for cholesterol excretion].

    Science.gov (United States)

    Blanchard, Claire; Moreau, François; Cariou, Bertrand; Le May, Cédric

    2014-10-01

    The small intestine plays a crucial role in dietary and biliary cholesterol absorption, as well as its lymphatic secretion as chylomicrons (lipoprotein exogenous way). Recently, a new metabolic pathway called TICE (trans-intestinal excretion of cholesterol) that plays a central role in cholesterol metabolism has emerged. TICE is an inducible way, complementary to the hepatobiliary pathway, allowing the elimination of the plasma cholesterol directly into the intestine lumen through the enterocytes. This pathway is poorly characterized but several molecular actors of TICE have been recently identified. Although it is a matter of debate, two independent studies suggest that TICE is involved in the anti-atherogenic reverse cholesterol transport pathway. Thus, TICE is an innovative drug target to reduce -cardiovascular diseases.

  16. 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.

  17. LDL cholesterol: controversies and future therapeutic directions.

    Science.gov (United States)

    Ridker, Paul M

    2014-08-16

    Lifelong exposure to raised concentrations of LDL cholesterol increases cardiovascular event rates, and the use of statin therapy as an adjunct to diet, exercise, and smoking cessation has proven highly effective in reducing the population burden associated with hyperlipidaemia. Yet, despite consistent biological, genetic, and epidemiological data, and evidence from randomised trials, there is controversy among national guidelines and clinical practice with regard to LDL cholesterol, its measurement, the usefulness of population-based screening, the net benefit-to-risk ratio for different LDL-lowering drugs, the benefit of treatment targets, and whether aggressive lowering of LDL is safe. Several novel therapies have been introduced for the treatment of people with genetic defects that result in loss of function within the LDL receptor, a major determinant of inherited hyperlipidaemias. Moreover, the usefulness of monoclonal antibodies that extend the LDL-receptor lifecycle (and thus result in substantial lowering of LDL cholesterol below the levels achieved with statins alone) is being assessed in phase 3 trials that will enrol more than 60,000 at-risk patients worldwide. These trials represent an exceptionally rapid translation of genetic observations into clinical practice and will address core questions of how low LDL cholesterol can be safely reduced, whether the mechanism of LDL-cholesterol lowering matters, and whether ever more aggressive lipid-lowering provides a safe, long-term mechanism to prevent atherothrombotic complications.

  18. A whole-body mathematical model of cholesterol metabolism and its age-associated dysregulation

    Directory of Open Access Journals (Sweden)

    Mc Auley Mark T

    2012-10-01

    Full Text Available Abstract Background Global demographic changes have stimulated marked interest in the process of aging. There has been, and will continue to be, an unrelenting rise in the number of the oldest old ( >85 years of age. Together with an ageing population there comes an increase in the prevalence of age related disease. Of the diseases of ageing, cardiovascular disease (CVD has by far the highest prevalence. It is regarded that a finely tuned lipid profile may help to prevent CVD as there is a long established relationship between alterations to lipid metabolism and CVD risk. In fact elevated plasma cholesterol, particularly Low Density Lipoprotein Cholesterol (LDL-C has consistently stood out as a risk factor for having a cardiovascular event. Moreover it is widely acknowledged that LDL-C may rise with age in both sexes in a wide variety of groups. The aim of this work was to use a whole-body mathematical model to investigate why LDL-C rises with age, and to test the hypothesis that mechanistic changes to cholesterol absorption and LDL-C removal from the plasma are responsible for the rise. The whole-body mechanistic nature of the model differs from previous models of cholesterol metabolism which have either focused on intracellular cholesterol homeostasis or have concentrated on an isolated area of lipoprotein dynamics. The model integrates both current and previously published data relating to molecular biology, physiology, ageing and nutrition in an integrated fashion. Results The model was used to test the hypothesis that alterations to the rate of cholesterol absorption and changes to the rate of removal of LDL-C from the plasma are integral to understanding why LDL-C rises with age. The model demonstrates that increasing the rate of intestinal cholesterol absorption from 50% to 80% by age 65 years can result in an increase of LDL-C by as much as 34 mg/dL in a hypothetical male subject. The model also shows that decreasing the rate of hepatic

  19. Oxidized LDL lipids increase β-amyloid production by SH-SY5Y cells through glutathione depletion and lipid raft formation.

    Science.gov (United States)

    Dias, Irundika H K; Mistry, Jayna; Fell, Shaun; Reis, Ana; Spickett, Corinne M; Polidori, Maria C; Lip, Gregory Y H; Griffiths, Helen R

    2014-10-01

    Elevated total cholesterol in midlife has been associated with increased risk of dementia in later life. We have previously shown that low-density lipoprotein (LDL) is more oxidized in the plasma of dementia patients, although total cholesterol levels are not different from those of age-matched controls. β-Amyloid (Aβ) peptide, which accumulates in Alzheimer disease (AD), arises from the initial cleavage of amyloid precursor protein by β-secretase-1 (BACE1). BACE1 activity is regulated by membrane lipids and raft formation. Given the evidence for altered lipid metabolism in AD, we have investigated a mechanism for enhanced Aβ production by SH-SY5Y neuronal-like cells exposed to oxidized LDL (oxLDL). The viability of SH-SY5Y cells exposed to 4μg oxLDL and 25µM 27-hydroxycholesterol (27OH-C) was decreased significantly. Lipids, but not proteins, extracted from oxLDL were more cytotoxic than oxLDL. In parallel, the ratio of reduced glutathione (GSH) to oxidized glutathione was decreased at sublethal concentrations of lipids extracted from native and oxLDL. GSH loss was associated with an increase in acid sphingomyelinase (ASMase) activity and lipid raft formation, which could be inhibited by the ASMase inhibitor desipramine. 27OH-C and total lipids from LDL and oxLDL independently increased Aβ production by SH-SY5Y cells, and Aβ accumulation could be inhibited by desipramine and by N-acetylcysteine. These data suggest a mechanism whereby oxLDL lipids and 27OH-C can drive Aβ production by GSH depletion, ASMase-driven membrane remodeling, and BACE1 activation in neuronal cells.

  20. Apical Localization of Sodium-Dependent Glucose Transporter SGLT1 is Maintained by Cholesterol and Microtubules

    OpenAIRE

    Suzuki, Takeshi; Matsuzaki, Toshiyuki; Hagiwara, Haruo; Aoki, Takeo; Tajika-Takahashi, Yukiko; Takata, Kuniaki

    2006-01-01

    A GFP-labeled sodium-dependent glucose transporter SGLT1 (SGLT-GFP) was transfected into MDCK cells. SGLT-GFP was localized at the apical membrane in confluent cells. When cellular cholesterol was depleted by methyl-β-cyclodextrin (MβCD) treatment, the localization of SGLT-GFP gradually switched from apical to whole plasma membrane. Time-lapse microscopy revealed that the effect of MβCD appeared within 30 min, and that the transition of SGLT-GFP to the whole plasma membrane was completed with...

  1. Mechanisms of Imidacloprid-Induced Alteration of Hypothalamic-Pituitary-Adrenal (HPA Axis after Subchronic Exposure in Male Rats

    Directory of Open Access Journals (Sweden)

    Alya Annabi

    2015-11-01

    Full Text Available Imidacloprid (IMI is known to target the nicotinic acetylcholine receptors (nAChRs in insects, and potentially in mammals. However, IMI toxicity on mammalian tissues has not been adequately evaluated. The aim of the present study was to examine whether IMI induced functional impairment in hypthalamic-pituitary-adrenal (HPA axis tissues. An oral exposure of 40 mg IMI/kg for 28 days in male rats caused a significant increase in malondialdehyde (MDA level. The antioxidant catalase, superoxide dismutase, and glutathione S-transferase showed various alterations following administration, but a significantly depleted thiol (SH groups was only recorded in hypothalamic tissues. The increase in the relative weight of adrenal glands and the increased adrenal cholesterol and plasma adrenocorticotropic hormone (ACTH levels are indicative of general adaptation syndrome. The hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased, highlighting the alteration of cholinergic transmission. In conclusion, the findings obtained show that chronic exposure to IMI may alter biochemical processes of HPA axis.

  2. 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....

  3. Clodronate treatment significantly depletes macrophages in chickens

    OpenAIRE

    Kameka, Amber M.; Haddadi, Siamak; Jamaldeen, Fathima Jesreen; Moinul, Prima; He, Xiao T.; Nawazdeen, Fathima Hafsa P.; Bonfield, Stephan; Sharif, Shayan; van Rooijen, Nico; Abdul-Careem, Mohamed Faizal

    2014-01-01

    Macrophages function as phagocytes and antigen-presenting cells in the body. As has been demonstrated in mammals, administration of clodronate [dichloromethylene bisphosphonate (Cl2MBP)] encapsulated liposomes results in depletion of macrophages. Although this compound has been used in chickens, its effectiveness in depleting macrophages has yet to be fully determined. Here, we show that a single administration of clodronate liposomes to chickens results in a significant depletion of macropha...

  4. Repulsive depletion interactions in colloid polymer mixtures

    OpenAIRE

    Rudhardt, Daniel; Bechinger, Clemens; Leiderer, Paul

    1999-01-01

    Depletion forces in colloidal systems are known to be entirely attractive, as long as the background of macromolecules is small enough that an ideal gas approach is valid. At higher densities, however, structural correlation effects of the macromolecules which lead to additional repulsive parts in the depletion interaction, have to be taken into account. We have measured the depletion interaction between a single polystyrene sphere and a wall in the presence of non-ionic polymer coils. Althou...

  5. Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans : a meta-analysis

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Katan, M.B.

    2001-01-01

    Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. Objective: The objective was to review the effect of dietary cholesterol o

  6. 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

  7. CHOBIMALT: a cholesterol-based detergent.

    Science.gov (United States)

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

    2010-11-01

    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 3−4 μM, 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.

  8. 50 CFR 216.15 - Depleted species.

    Science.gov (United States)

    2010-10-01

    ... Assistant Administrator as depleted under the provisions of the MMPA. (a) Hawaiian monk seal (Monachus schauinslandi). (b) Bowhead whale (Balaena mysticetus). (c) North Pacific fur seal (Callorhinus...

  9. Ego depletion increases risk-taking.

    Science.gov (United States)

    Fischer, Peter; Kastenmüller, Andreas; Asal, Kathrin

    2012-01-01

    We investigated how the availability of self-control resources affects risk-taking inclinations and behaviors. We proposed that risk-taking often occurs from suboptimal decision processes and heuristic information processing (e.g., when a smoker suppresses or neglects information about the health risks of smoking). Research revealed that depleted self-regulation resources are associated with reduced intellectual performance and reduced abilities to regulate spontaneous and automatic responses (e.g., control aggressive responses in the face of frustration). The present studies transferred these ideas to the area of risk-taking. We propose that risk-taking is increased when individuals find themselves in a state of reduced cognitive self-control resources (ego-depletion). Four studies supported these ideas. In Study 1, ego-depleted participants reported higher levels of sensation seeking than non-depleted participants. In Study 2, ego-depleted participants showed higher levels of risk-tolerance in critical road traffic situations than non-depleted participants. In Study 3, we ruled out two alternative explanations for these results: neither cognitive load nor feelings of anger mediated the effect of ego-depletion on risk-taking. Finally, Study 4 clarified the underlying psychological process: ego-depleted participants feel more cognitively exhausted than non-depleted participants and thus are more willing to take risks. Discussion focuses on the theoretical and practical implications of these findings. PMID:22931000

  10. 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.

  11. Cholesterol Metabolism in Brain and Skin Fibroblasts from Sarda Breed Sheep With Scrapie-resistant and Scrapie-susceptible Genotypes

    Directory of Open Access Journals (Sweden)

    Alessandra Pani

    2007-01-01

    Full Text Available Scrapie is a fatal spongiform encephalopathy of sheep, a transmissible form of prion disease caused by neuronal accumulation of the aberrantly conformed prion protein (PrPsc. Currently, no ante-mortem diagnostic tests are available to detect this untreatable disease in the pre-clinical stage, thus making difficult to control its spread. Recent evidence suggests that the production of PrPsc can be modulated by the levels of membrane cholesterol in neuronal cells. Since cholesterol levels in cell membranes are dependent on cholesterol homeostasis in the whole organism, we studied cholesterol metabolism in brain tissues, plasma and skin fibroblasts of Sarda breed sheep with scrapie-resistant (ARR/ARR and scrapie-susceptible (ARQ/ARQ prion protein genotypes, both not infected (ARQ/ARQ- and infected (ARQ/ARQ+ with scrapie. We found that, the levels of cytoplasmic cholesterol esters (CE in brains and skin fibroblasts from sheep with the ARQ/ARQ genotype were consistently higher than those from sheep with the ARR/ARR genotype. Conversely, the levels of free cholesterol (FC were lower in ARQ/ARQ, as compared to ARR/ARR sheep, thus resulting in a sharp reduction of the FC/CE ratio. Moreover, both uninfected and infected ARQ/ARQ sheep showed abnormally low levels of high density lipoprotein-cholesterol (HDL-C in their plasma, as compared to ARR/ARR sheep. These data other than adding new strength to the notion that altered levels of intracellular cholesterol may indicate the presence of a lipid metabolic state that predisposes to infection with, and accumulation of, PrPsc in the brain, discriminate for the first time between two distinct but related cellular pools of cholesterol, namely membrane FC on one hand and cytoplasmic CE on the other.

  12. Dystroglycan depletion inhibits the functions of differentiated HL-60 cells.

    Science.gov (United States)

    Martínez-Zárate, Alma Delia; Martínez-Vieyra, Ivette; Alonso-Rangel, Lea; Cisneros, Bulmaro; Winder, Steve J; Cerecedo, Doris

    2014-06-01

    Dystroglycan has recently been characterized in blood tissue cells, as part of the dystrophin glycoprotein complex but to date nothing is known of its role in the differentiation process of neutrophils. We have investigated the role of dystroglycan in the human promyelocytic leukemic cell line HL-60 differentiated to neutrophils. Depletion of dystroglycan by RNAi resulted in altered morphology and reduced properties of differentiated HL-60 cells, including chemotaxis, respiratory burst, phagocytic activities and expression of markers of differentiation. These findings strongly implicate dystroglycan as a key membrane adhesion protein involved in the differentiation process in HL-60 cells.

  13. 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)

  14. Ordering effects of cholesterol and its analogues

    DEFF Research Database (Denmark)

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

    2009-01-01

    . 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 approaches....

  15. 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

  16. Depleted argon from underground sources

    Energy Technology Data Exchange (ETDEWEB)

    Back, H.O.; /Princeton U.; Alton, A.; /Augustana U. Coll.; Calaprice, F.; Galbiati, C.; Goretti, A.; /Princeton U.; Kendziora, C.; /Fermilab; Loer, B.; /Princeton U.; Montanari, D.; /Fermilab; Mosteiro, P.; /Princeton U.; Pordes, S.; /Fermilab

    2011-09-01

    Argon is a powerful scintillator and an excellent medium for detection of ionization. Its high discrimination power against minimum ionization tracks, in favor of selection of nuclear recoils, makes it an attractive medium for direct detection of WIMP dark matter. However, cosmogenic {sup 39}Ar contamination in atmospheric argon limits the size of liquid argon dark matter detectors due to pile-up. The cosmic ray shielding by the earth means that Argon from deep underground is depleted in {sup 39}Ar. In Cortez Colorado a CO{sub 2} well has been discovered to contain approximately 500ppm of argon as a contamination in the CO{sub 2}. In order to produce argon for dark matter detectors we first concentrate the argon locally to 3-5% in an Ar, N{sub 2}, and He mixture, from the CO{sub 2} through chromatographic gas separation. The N{sub 2} and He will be removed by continuous cryogenic distillation in the Cryogenic Distillation Column recently built at Fermilab. In this talk we will discuss the entire extraction and purification process; with emphasis on the recent commissioning and initial performance of the cryogenic distillation column purification.

  17. A cholesterol-binding domain in STIM1 modulates STIM1-Orai1 physical and functional interactions.

    Science.gov (United States)

    Pacheco, Jonathan; Dominguez, Laura; Bohórquez-Hernández, A; Asanov, Alexander; Vaca, Luis

    2016-01-01

    STIM1 and Orai1 are the main components of a widely conserved Calcium influx pathway known as store-operated calcium entry (SOCE). STIM1 is a calcium sensor, which oligomerizes and activates Orai channels when calcium levels drop inside the endoplasmic reticulum (ER). The series of molecular rearrangements that STIM1 undergoes until final activation of Orai1 require the direct exposure of the STIM1 domain known as SOAR (Stim Orai Activating Region). In addition to these complex molecular rearrangements, other constituents like lipids at the plasma membrane, play critical roles orchestrating SOCE. PI(4,5)P2 and enriched cholesterol microdomains have been shown as important signaling platforms that recruit the SOCE machinery in steps previous to Orai1 activation. However, little is known about the molecular role of cholesterol once SOCE is activated. In this study we provide clear evidence that STIM1 has a cholesterol-binding domain located inside the SOAR region and modulates Orai1 channels. We demonstrate a functional association of STIM1 and SOAR to cholesterol, indicating a close proximity of SOAR to the inner layer of the plasma membrane. In contrast, the depletion of cholesterol induces the SOAR detachment from the plasma membrane and enhances its association to Orai1. These results are recapitulated with full length STIM1. PMID:27459950

  18. Characteristics of High-density Lipoprotein Subclasses Distribution for Subjects with Desirable Total Cholesterol Levels

    OpenAIRE

    Xu Yanhua; Liu Yinghui; Fu Mingde; Long Shiyin; Tian Li; Jia Lianqun

    2011-01-01

    Abstract Background To investigate alteration of high density lipoproteins (HDL) subclasses distribution in different total cholesterol (TC) levels, mainly the characteristics of HDL subclasses distribution in desirable TC levels and analyze the related mechanisms. Methods ApoA-I contents of plasma HDL subclasses were determined by 2-dimensional gel electrophoresis coupled with immunodetection. 486 Chinese Adults subjects were assigned to different TC groups according to the third Report of N...

  19. The usefulness of information on HDL-cholesterol: potential pitfalls of conventional assumptions

    OpenAIRE

    Furberg Curt D

    2001-01-01

    Abstract Treatment decisions related to disease prevention are often based on two conventional and related assumptions. First, an intervention-induced change in a surrogate marker (such as high-density lipoprotein [HDL]-cholesterol) in the desired direction translates into health benefits (such as reduction in coronary events). Second, it is unimportant which interventions are used to alter surrogate markers, since an intervention benefit is independent of the means by which it is achieved. T...

  20. Carotid artery stiffness, high-density lipoprotein cholesterol and inflammation in men with pre-hypertension

    OpenAIRE

    Heffernan, Kevin S; Karas, Richard H.; Kuvin, Jeffrey T.; Jae, Sae Young; Vieira, Victoria J.; Fernhall, Bo

    2009-01-01

    Low circulating levels of high density lipoprotein cholesterol (HDL-C) are associated with increased risk for cardiovascular events. HDL-C has a variety of poorly understood atheroprotective effects, including altering lipid metabolism and reducing inflammation. Increased arterial stiffness is an important predictor of subsequent cardiovascular risk. Therefore, in the current study, we sought to determine whether HDL-C levels are associated with carotid arterial stiffness. In addition we exam...

  1. Remnant cholesterol as a cause of ischemic heart disease

    DEFF Research Database (Denmark)

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

    2014-01-01

    levels of remnant cholesterol may cause atherosclerosis same way as elevated levels of low-density lipoprotein (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1mmol/L (39mg....... However, elevated levels of LDL cholesterol are associated with IHD, but not with low-grade inflammation. Such results indicate that elevated LDL cholesterol levels cause atherosclerosis without a major inflammatory component, whereas an inflammatory component of atherosclerosis is driven by elevated...

  2. Alterations of lipid metabolism in Wilson disease

    OpenAIRE

    Stremmel Wolfgang; Eckert Nicola; Pfeiffenberger Jan; Gotthardt Daniel; Gohdes Annina; Seessle Jessica; Reuner Ulrike; Weiss Karl

    2011-01-01

    Abstract Introduction Wilson disease (WD) is an inherited disorder of human copper metabolism, characterised by accumulation of copper predominantly in the liver and brain, leading to severe hepatic and neurological disease. Interesting findings in animal models of WD (Atp7b-/- and LEC rats) showed altered lipid metabolism with a decrease in the amount of triglycerides and cholesterol in the serum. However, serum lipid profile has not been investigated in large human WD patient cohorts to dat...

  3. Histone deacetylase inhibition decreases cholesterol levels in neuronal cells by modulating key genes in cholesterol synthesis, uptake and efflux.

    Directory of Open Access Journals (Sweden)

    Maria João Nunes

    Full Text Available Cholesterol is an essential component of the central nervous system and increasing evidence suggests an association between brain cholesterol metabolism dysfunction and the onset of neurodegenerative disorders. Interestingly, histone deacetylase inhibitors (HDACi such as trichostatin A (TSA are emerging as promising therapeutic approaches in neurodegenerative diseases, but their effect on brain cholesterol metabolism is poorly understood. We have previously demonstrated that HDACi up-regulate CYP46A1 gene transcription, a key enzyme in neuronal cholesterol homeostasis. In this study, TSA was shown to modulate the transcription of other genes involved in cholesterol metabolism in human neuroblastoma cells, namely by up-regulating genes that control cholesterol efflux and down-regulating genes involved in cholesterol synthesis and uptake, thus leading to an overall decrease in total cholesterol content. Furthermore, co-treatment with the amphipathic drug U18666A that can mimic the intracellular cholesterol accumulation observed in cells of Niemman-Pick type C patients, revealed that TSA can ameliorate the phenotype induced by pathological cholesterol accumulation, by restoring the expression of key genes involved in cholesterol synthesis, uptake and efflux and promoting lysosomal cholesterol redistribution. These results clarify the role of TSA in the modulation of neuronal cholesterol metabolism at the transcriptional level, and emphasize the idea of HDAC inhibition as a promising therapeutic tool in neurodegenerative disorders with impaired cholesterol metabolism.

  4. Impact of ozone depletion on immune function

    Energy Technology Data Exchange (ETDEWEB)

    Jeevan, A.; Kripke, M.L. (Univ. of Texas, Houston, TX (United States). Dept. of Immunology)

    1993-06-01

    Depletion of stratospheric ozone is expected to lead to an increase in the amount of UV-B radiation present in sunlight. In addition to its well known ability to cause skin cancer, UV-B radiation has been shown to alter the immune system. The immune system is the body's primary defense mechanism against infectious diseases and protects against the development of certain types of cancer. Any impairment of immune function may jeopardize health by increasing susceptibility to infectious diseases, increasing the severity of infections, or delaying recovery for infections. In addition, impaired immune function can increase the incidence of certain cancers, particularly cancers of the skin. Research carried out with laboratory animals over the past 15 years has demonstrated that exposure of the skin to UV-B radiation can suppress certain types of immune responses. These include rejection of UV-induced skin cancers and melanomas, contact allergy reactions to chemicals, delayed-type hypersensitivity responses to microbial and other antigens, and phagocytosis and elimination of certain bacteria from lymphoid tissues. Recent studies with mycobacterial infection of mice demonstrated that exposure to UV-B radiation decreased the delayed hypersensitivity response to mycobacterial antigens and increased the severity of infection. In humans, UV-B radiation has also been shown to impair the contact allergy response. These studies demonstrate that UV radiation can decrease immune responses in humans and laboratory and raise the possibility that increased exposure to UV-B radiation could adversely affect human health by increasing the incidence or severity of certain infectious diseases.

  5. Oil depletion and terms of trade

    OpenAIRE

    Irimia-Vladu, Marina; Thompson, Henry

    2007-01-01

    A model of the international oil market model with optimal depletion and offer curves suggests importers face a backward bending offer curve. An oil tariff would then raise oil imports and lower the price of oil including the tariff. Simulations of price and extraction paths for the coming century provide insight into the future of oil depletion and terms of trade.

  6. Depletion sensitivity predicts unhealthy snack purchases

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; Fennis, Bob M.; De Vet, Emely; De Ridder, Denise T D

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose we

  7. Depletion sensitivity predicts unhealthy snack purchases

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; Fennis, Bob M.; Vet, De Emely; Ridder, De Denise T.D.

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose

  8. The Chemistry and Toxicology of Depleted Uranium

    Directory of Open Access Journals (Sweden)

    Sidney A. Katz

    2014-03-01

    Full Text Available Natural uranium is comprised of three radioactive isotopes: 238U, 235U, and 234U. Depleted uranium (DU is a byproduct of the processes for the enrichment of the naturally occurring 235U isotope. The world wide stock pile contains some 1½ million tons of depleted uranium. Some of it has been used to dilute weapons grade uranium (~90% 235U down to reactor grade uranium (~5% 235U, and some of it has been used for heavy tank armor and for the fabrication of armor-piercing bullets and missiles. Such weapons were used by the military in the Persian Gulf, the Balkans and elsewhere. The testing of depleted uranium weapons and their use in combat has resulted in environmental contamination and human exposure. Although the chemical and the toxicological behaviors of depleted uranium are essentially the same as those of natural uranium, the respective chemical forms and isotopic compositions in which they usually occur are different. The chemical and radiological toxicity of depleted uranium can injure biological systems. Normal functioning of the kidney, liver, lung, and heart can be adversely affected by depleted uranium intoxication. The focus of this review is on the chemical and toxicological properties of depleted and natural uranium and some of the possible consequences from long term, low dose exposure to depleted uranium in the environment.

  9. 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

  10. [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

  11. Ionospheric heating, upwelling, and depletions in auroral current systems

    Science.gov (United States)

    Zettergren, M. D.; Semeter, J. L.

    2010-12-01

    This research investigates aspects of ionospheric dynamics relevant to magnetosphere-ionosphere coupling in auroral arc current systems. Auroral electric fields and particle precipitation deposit energy in the ionosphere, often resulting in enhanced ion or electron temperatures. This heating has a wide variety of consequences for the ionosphere. High ion temperatures alter chemical balance in the lower F-region, resulting in conversion to a molecular ion plasma, faster recombination, and plasma depletions. Pressure enhancements resulting from both ion and electron heating are capable of generating intense ion upflows. Ion upflow and depletion processes redistribute and structure the auroral plasma in ways that are likely of consequence to wave coupling of the magnetosphere and ionosphere. These implications are examined through the use of a fluid-kinetic model of the auroral ionosphere and new incoherent scatter radar data analysis techniques. Results indicate that enhanced recombination of molecular ions in auroral downward current regions may work in concert with well-known electrodynamic depletion processes, in the F-region ionosphere. Furthermore, ionospheric upflows in auroral upward and downward current regions may be quite different in terms of intensity and types of upflowing ions.

  12. Specification for the VERA Depletion Benchmark Suite

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kang Seog [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-12-17

    CASL-X-2015-1014-000 iii Consortium for Advanced Simulation of LWRs EXECUTIVE SUMMARY The CASL neutronics simulator MPACT is under development for the neutronics and T-H coupled simulation for the pressurized water reactor. MPACT includes the ORIGEN-API and internal depletion module to perform depletion calculations based upon neutron-material reaction and radioactive decay. It is a challenge to validate the depletion capability because of the insufficient measured data. One of the detoured methods to validate it is to perform a code-to-code comparison for benchmark problems. In this study a depletion benchmark suite has been developed and a detailed guideline has been provided to obtain meaningful computational outcomes which can be used in the validation of the MPACT depletion capability.

  13. The usefulness of information on HDL-cholesterol: potential pitfalls of conventional assumptions

    Directory of Open Access Journals (Sweden)

    Furberg Curt D

    2001-05-01

    Full Text Available Abstract Treatment decisions related to disease prevention are often based on two conventional and related assumptions. First, an intervention-induced change in a surrogate marker (such as high-density lipoprotein [HDL]-cholesterol in the desired direction translates into health benefits (such as reduction in coronary events. Second, it is unimportant which interventions are used to alter surrogate markers, since an intervention benefit is independent of the means by which it is achieved. The scientific foundation for these assumptions has been questioned. In this commentary, the appropriateness of relying on low levels of HDL-cholesterol for treatment decisions is reviewed. The Veterans Affairs - HDL-Cholesterol Intervention Trial (VA-HIT investigators recently reported that only 23% of the gemfibrozil-induced relative reduction in risk of coronary events observed in the trial could be explained by changes in HDL-cholesterol between baseline and the 1-year visit. Thus, 77% of the health benefit to the participants was unexplained. Other possible explanations are that gemfibrozil has multiple mechanisms of action, disease manifestations are multifactorial, and laboratory measurements of HDL-cholesterol are imprecise. The wisdom of relying on levels and changes in surrogate markers such as HDL-cholesterol to make decisions about treatment choices should questioned. It seems better to rely on direct evidence of health benefits and to prescribe specific interventions that have been shown to reduce mortality and morbidity. Since extrapolations based on surrogate markers may not be in patients' best interest, the practice of medicine ought to be evidence-based.

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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....

  19. 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 ...

  20. 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 ...

  1. CRDIAC: Coupled Reactor Depletion Instrument with Automated Control

    Energy Technology Data Exchange (ETDEWEB)

    Steven K. Logan

    2012-08-01

    When modeling the behavior of a nuclear reactor over time, it is important to understand how the isotopes in the reactor will change, or transmute, over that time. This is especially important in the reactor fuel itself. Many nuclear physics modeling codes model how particles interact in the system, but do not model this over time. Thus, another code is used in conjunction with the nuclear physics code to accomplish this. In our code, Monte Carlo N-Particle (MCNP) codes and the Multi Reactor Transmutation Analysis Utility (MRTAU) were chosen as the codes to use. In this way, MCNP would produce the reaction rates in the different isotopes present and MRTAU would use cross sections generated from these reaction rates to determine how the mass of each isotope is lost or gained. Between these two codes, the information must be altered and edited for use. For this, a Python 2.7 script was developed to aid the user in getting the information in the correct forms. This newly developed methodology was called the Coupled Reactor Depletion Instrument with Automated Controls (CRDIAC). As is the case in any newly developed methodology for modeling of physical phenomena, CRDIAC needed to be verified against similar methodology and validated against data taken from an experiment, in our case AFIP-3. AFIP-3 was a reduced enrichment plate type fuel tested in the ATR. We verified our methodology against the MCNP Coupled with ORIGEN2 (MCWO) method and validated our work against the Post Irradiation Examination (PIE) data. When compared to MCWO, the difference in concentration of U-235 throughout Cycle 144A was about 1%. When compared to the PIE data, the average bias for end of life U-235 concentration was about 2%. These results from CRDIAC therefore agree with the MCWO and PIE data, validating and verifying CRDIAC. CRDIAC provides an alternative to using ORIGEN-based methodology, which is useful because CRDIAC's depletion code, MRTAU, uses every available isotope in its

  2. 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.

  3. α-Tocopherol adipose tissue stores are depleted after burn injury in pediatric patients123

    OpenAIRE

    Traber, Maret G.; Leonard, Scott W.; Traber, Daniel L; Traber, Lillian D; Gallagher, James; Bobe, Gerd; Jeschke, Marc G.; Finnerty, Celeste C.; Herndon, David

    2010-01-01

    Background: We previously showed that thermal injury depletes plasma vitamin E in pediatric burn patients; however, plasma changes may reflect immediate alterations in vitamin E nutriture. Adipose tissue α-tocopherol concentrations are generally accepted to reflect long-term vitamin E status.

  4. 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.

  5. Osbpl8 Deficiency in Mouse Causes an Elevation of High-Density Lipoproteins and Gender-Specific Alterations of Lipid Metabolism

    Science.gov (United States)

    Béaslas, Olivier; Metso, Jari; Nissilä, Eija; Laurila, Pirkka-Pekka; Kaiharju, Essi; Batchu, Krishna Chaithanya; Kaipiainen, Leena; Mäyränpää, Mikko I.; Yan, Daoguang; Gylling, Helena; Jauhiainen, Matti; Olkkonen, Vesa M.

    2013-01-01

    OSBP-related protein 8 (ORP8) encoded by Osbpl8 is an endoplasmic reticulum sterol sensor implicated in cellular lipid metabolism. We generated an Osbpl8−/− (KO) C57Bl/6 mouse strain. Wild-type and Osbpl8KO animals at the age of 13-weeks were fed for 5 weeks either chow or high-fat diet, and their plasma lipids/lipoproteins and hepatic lipids were analyzed. The chow-fed Osbpl8KO male mice showed a marked elevation of high-density lipoprotein (HDL) cholesterol (+79%) and phospholipids (+35%), while only minor increase of apolipoprotein A-I (apoA-I) was detected. In chow-fed female KO mice a less prominent increase of HDL cholesterol (+27%) was observed, while on western diet the HDL increment was prominent in both genders. The HDL increase was accompanied by an elevated level of HDL-associated apolipoprotein E in male, but not female KO animals. No differences between genotypes were observed in lecithin:cholesterol acyltransferase (LCAT) or hepatic lipase (HL) activity, or in the fractional catabolic rate of fluorescently labeled mouse HDL injected in chow-diet fed animals. The Osbpl8KO mice of both genders displayed reduced phospholipid transfer protein (PLTP) activity, but only on chow diet. These findings are consistent with a model in which Osbpl8 deficiency results in altered biosynthesis of HDL. Consistent with this hypothesis, ORP8 depleted mouse hepatocytes secreted an increased amount of nascent HDL into the culture medium. In addition to the HDL phenotype, distinct gender-specific alterations in lipid metabolism were detected: Female KO animals on chow diet showed reduced lipoprotein lipase (LPL) activity and increased plasma triglycerides, while the male KO mice displayed elevated plasma cholesterol biosynthetic markers cholestenol, desmosterol, and lathosterol. Moreover, modest gender-specific alterations in the hepatic expression of lipid homeostatic genes were observed. In conclusion, we report the first viable OsbplKO mouse model, demonstrating a

  6. Unsaturated fatty acids and phytosterols regulate cholesterol transporter genes in Caco-2 and HepG2 cell lines.

    Science.gov (United States)

    Park, Youngki; Carr, Timothy P

    2013-02-01

    Dietary consumption of phytosterols and certain fatty acids has been shown to reduce cholesterol absorption and plasma cholesterol concentrations. However, it has not been fully elucidated whether phytosterols or fatty acids can alter the expression of cholesterol transporters by functioning as signaling molecules. This study tested the hypothesis that various fatty acids and phytosterols commonly found in the food supply can modulate the expression of transporters including Niemann-Pick C1-like 1, low-density lipoprotein receptor, and scavenger receptor class B type I and 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the intestine and liver. Caco-2 cells were used as models of enterocytes, and HepG2 cells were used as a model of hepatocytes. The cells were treated for 18 hours with 100 μmol/L of a fatty acid, or for 24 hours with 10 μmol/L of 25α-hydroxycholesterol, or 100 μmol/L of cholesterol, sitosterol, and stigmasterol to measure expression of genes involved in cholesterol transport using quantitative real-time polymerase chain reaction. Polyunsaturated fatty acids in Caco-2 cells and sterols in HepG2 cells significantly reduced the messenger RNA expression levels of Niemann-Pick C1-like 1, scavenger receptor class B type I, low-density lipoprotein receptor, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Importantly, sitosterol and stigmasterol reduced the messenger RNA levels of genes to a similar extent as cholesterol. The data support the hypothesis that unsaturated fatty acid and phytosterols can act as signaling molecules and alter the expression of genes involved in cholesterol transport and metabolism.

  7. 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}.

  8. The Interleukin-6 inflammation pathway from cholesterol to aging – Role of statins, bisphosphonates and plant polyphenols in aging and age-related diseases

    Directory of Open Access Journals (Sweden)

    Omoigui Sota

    2007-03-01

    Full Text Available Abstract We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation.

  9. Moderate alcohol consumption increases cholesterol efflux mediated by ABCA1

    NARCIS (Netherlands)

    Beulens, J.W.J.; Sierksma, A.; Tol, van A.; Fournier, C.

    2004-01-01

    Moderate alcohol consumption increases HDL cholesterol, which is involved in reverse cholesterol transport (RCT). The aim of this study was to investigate the effect of moderate alcohol consumption on cholesterol efflux, using J774 mouse macrophages and Fu5AH cells, and on other parameters in the RC

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

    NARCIS (Netherlands)

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

    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

  11. Understanding Lipoproteins as Transporters of Cholesterol and Other Lipids

    Science.gov (United States)

    Biggerstaff, Kyle D.; Wooten, Joshua S.

    2004-01-01

    A clear picture of lipoprotein metabolism is essential for understanding the pathophysiology of atherosclerosis. Many students are taught that low-density lipoprotein-cholesterol is "bad" and high-density lipoprotein-cholesterol is "good." This misconception leads to students thinking that lipoproteins are types of cholesterol rather than…

  12. 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...

  13. 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)

  14. 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

  15. 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 as...

  16. Carbon Inverse Opal Rods for Nonenzymatic Cholesterol Detection.

    Science.gov (United States)

    Zhong, Qifeng; Xie, Zhuoying; Ding, Haibo; Zhu, Cun; Yang, Zixue; Gu, Zhongze

    2015-11-18

    Carbon inverse opal rods made from silica photonic crystal rods are used for nonenzymatic cholesterol sensing. The characteristic reflection peak originating from the physical periodic structure works as sensing signals for quantitatively estimating cholesterol concentrations. Carbon inverse opal rods work both in cholesterol standard solutions and human serum. They are suitable for practical use in clinical diagnose.

  17. 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

  18. 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

  19. 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

  20. Impact of Inhibiting Ileal Apical Versus Basolateral Bile acid Transport on Cholesterol Metabolism and Atherosclerosis in Mice

    Science.gov (United States)

    Dawson, Paul A.

    2015-01-01

    Background Bile acid sequestrants have been used for many years to treat hypercholesterolemia by increasing hepatic conversion of cholesterol to bile acids, thereby inducing hepatic LDL receptor expression and clearance of apoB-containing particles. In order to further understand the underlying molecular mechanisms linking gut-liver signaling and cholesterol homeostasis, mouse models defective in ileal apical membrane bile acid transport (Asbt null) and ileal basolateral membrane bile acid transport (Ostα null) were studied under basal and hypercholesterolemic conditions. Key Messages Hepatic conversion of cholesterol to bile acids is the major pathway for cholesterol catabolism and a major mechanism for cholesterol elimination. Blocking ileal apical membrane bile acid transport (Asbt null mice) increases fecal bile acid excretion, hepatic Cyp7a1 expression and the relative proportion of taurocholate in the bile acid pool, but decreases ileal FGF15 expression, bile acid pool size, and hepatic cholesterol content. In contrast, blocking ileal basolateral membrane bile acid transport (Ostα null mice) increases ileal FGF15 expression, reduces hepatic Cyp7a1 expression, and increases the proportion of tauro-β-muricholic acid in the bile acid pool. In the hypercholesterolemic apoE null background, plasma cholesterol levels and measurements of atherosclerosis were reduced in Asbt/apoE null mice but not in Ostα/apoE null mice. Conclusions Blocking intestinal absorption of bile acids at the apical versus basolateral membrane differentially affects bile acid and cholesterol metabolism, including the development of hypercholesterolemia-associated atherosclerosis. The molecular mechanism likely involves altered regulation of ileal FGF15 expression. PMID:26045273

  1. β-Cyclodextrins Decrease Cholesterol Release and ABC-Associated Transporter Expression in Smooth Muscle Cells and Aortic Endothelial Cells

    Science.gov (United States)

    Coisne, Caroline; Hallier-Vanuxeem, Dorothée; Boucau, Marie-Christine; Hachani, Johan; Tilloy, Sébastien; Bricout, Hervé; Monflier, Eric; Wils, Daniel; Serpelloni, Michel; Parissaux, Xavier; Fenart, Laurence; Gosselet, Fabien

    2016-01-01

    Atherosclerosis is an inflammatory disease that leads to an aberrant accumulation of cholesterol in vessel walls forming atherosclerotic plaques. During this process, the mechanism regulating complex cellular cholesterol pools defined as the reverse cholesterol transport (RCT) is altered as well as expression and functionality of transporters involved in this process, namely ABCA1, ABCG1, and SR-BI. Macrophages, arterial endothelial and smooth muscle cells (SMCs) have been involved in the atherosclerotic plaque formation. As macrophages are widely described as the major cell type forming the foam cells by accumulating intracellular cholesterol, RCT alterations have been poorly studied at the arterial endothelial cell and SMC levels. Amongst the therapeutics tested to actively counteract cellular cholesterol accumulation, the methylated β-cyclodextrin, KLEPTOSE® CRYSMEβ, has recently shown promising effects on decreasing the atherosclerotic plaque size in atherosclerotic mouse models. Therefore we investigated in vitro the RCT process occurring in SMCs and in arterial endothelial cells (ABAE) as well as the ability of some modified β-CDs with different methylation degree to modify RCT in these cells. To this aim, cells were incubated in the presence of different methylated β-CDs, including KLEPTOSE® CRYSMEβ. Both cell types were shown to express basal levels of ABCA1 and SR-BI whereas ABCG1 was solely found in ABAE. Upon CD treatments, the percentage of membrane-extracted cholesterol correlated to the methylation degree of the CDs independently of the lipid composition of the cell membranes. Decreasing the cellular cholesterol content with CDs led to reduce the expression levels of ABCA1 and ABCG1. In addition, the cholesterol efflux to ApoA-I and HDL particles was significantly decreased suggesting that cells forming the blood vessel wall are able to counteract the CD-induced loss of cholesterol. Taken together, our observations suggest that methylated

  2. 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 ...

  3. 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...

  4. A genome-wide RNAi screen identifies regulators of cholesterol-modified hedgehog secretion in Drosophila.

    Directory of Open Access Journals (Sweden)

    Reid Aikin

    Full Text Available Hedgehog (Hh proteins are secreted molecules that function as organizers in animal development. In addition to being palmitoylated, Hh is the only metazoan protein known to possess a covalently-linked cholesterol moiety. The absence of either modification severely disrupts the organization of numerous tissues during development. It is currently not known how lipid-modified Hh is secreted and released from producing cells. We have performed a genome-wide RNAi screen in Drosophila melanogaster cells to identify regulators of Hh secretion. We found that cholesterol-modified Hh secretion is strongly dependent on coat protein complex I (COPI but not COPII vesicles, suggesting that cholesterol modification alters the movement of Hh through the early secretory pathway. We provide evidence that both proteolysis and cholesterol modification are necessary for the efficient trafficking of Hh through the ER and Golgi. Finally, we identified several putative regulators of protein secretion and demonstrate a role for some of these genes in Hh and Wingless (Wg morphogen secretion in vivo. These data open new perspectives for studying how morphogen secretion is regulated, as well as provide insight into regulation of lipid-modified protein secretion.

  5. Tailoring Bicelle Morphology and Thermal Stability with Lanthanide-Chelating Cholesterol Conjugates.

    Science.gov (United States)

    Isabettini, Stéphane; Liebi, Marianne; Kohlbrecher, Joachim; Ishikawa, Takashi; Windhab, Erich J; Fischer, Peter; Walde, Peter; Kuster, Simon

    2016-09-01

    Bicelles composed of DMPC and phospholipids capable of chelating lanthanide ions, such as 1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylene triaminepentaacetate (DMPE-DTPA), are highly tunable magnetically responsive soft materials. Further doping of these systems with cholesterol-DTPA conjugates complexed to a lanthanide ion considerably enhances the bicelle's size and magnetic alignability. The high value of these cholesterol conjugates for bicelle design remains largely unexplored. Herein, we examine how molecular structural alterations within the cholesterol-DTPA conjugates lead to contrasting self-assembled polymolecular aggregate structures when incorporated into DMPC/DMPE-DTPA/Tm(3+) bilayers. The nature of the linker connecting the DTPA-chelating moiety to the sterol backbone is examined by synthesizing conjugates of various linker lengths and polarities. The incorporation of these compounds within the bilayer results in polymolecular aggregate geometries of higher curvature. The increasing degrees of freedom for conformational changes conveyed to the chelator headgroup with increasing linker atomic length reduce the cholesterol-DTPA conjugate's critical packing parameter. Consequently, an inverse correlation between the number of carbon atoms in the linker and the bicelle radius is established. The introduction of polarity into the carbon chain of the linker did not cause major changes in the polymolecular aggregate architecture. Under specific conditions, the additives permit the formation of remarkably temperature-resistant bicelles. The versatility of design offered by these amphiphiles gives rise to new and viable tools for the growing field of magnetically responsive soft materials. PMID:27529644

  6. Host cell P-glycoprotein is essential for cholesterol uptake and replication of Toxoplasma gondii.

    Science.gov (United States)

    Bottova, Iveta; Hehl, Adrian B; Stefanić, Sasa; Fabriàs, Gemma; Casas, Josefina; Schraner, Elisabeth; Pieters, Jean; Sonda, Sabrina

    2009-06-26

    P-glycoprotein (P-gp) is a membrane-bound efflux pump that actively exports a wide range of compounds from the cell and is associated with the phenomenon of multidrug resistance. However, the role of P-gp in normal physiological processes remains elusive. Using P-gp-deficient fibroblasts, we showed that P-gp was critical for the replication of the intracellular parasite Toxoplasma gondii but was not involved in invasion of host cells by the parasite. Importantly, we found that the protein participated in the transport of host-derived cholesterol to the intracellular parasite. T. gondii replication in P-gp-deficient host cells not only resulted in reduced cholesterol content in the parasite but also altered its sphingolipid metabolism. In addition, we found that different levels of P-gp expression modified the cholesterol metabolism in uninfected fibroblasts. Collectively our findings reveal a key and previously undocumented role of P-gp in host-parasite interaction and suggest a physiological role for P-gp in cholesterol trafficking in mammalian cells. PMID:19389707

  7. Host Cell P-glycoprotein Is Essential for Cholesterol Uptake and Replication of Toxoplasma gondii*

    Science.gov (United States)

    Bottova, Iveta; Hehl, Adrian B.; Štefanić, Saša; Fabriàs, Gemma; Casas, Josefina; Schraner, Elisabeth; Pieters, Jean; Sonda, Sabrina

    2009-01-01

    P-glycoprotein (P-gp) is a membrane-bound efflux pump that actively exports a wide range of compounds from the cell and is associated with the phenomenon of multidrug resistance. However, the role of P-gp in normal physiological processes remains elusive. Using P-gp-deficient fibroblasts, we showed that P-gp was critical for the replication of the intracellular parasite Toxoplasma gondii but was not involved in invasion of host cells by the parasite. Importantly, we found that the protein participated in the transport of host-derived cholesterol to the intracellular parasite. T. gondii replication in P-gp-deficient host cells not only resulted in reduced cholesterol content in the parasite but also altered its sphingolipid metabolism. In addition, we found that different levels of P-gp expression modified the cholesterol metabolism in uninfected fibroblasts. Collectively our findings reveal a key and previously undocumented role of P-gp in host-parasite interaction and suggest a physiological role for P-gp in cholesterol trafficking in mammalian cells. PMID:19389707

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

    Science.gov (United States)

    ... cholesterol throughout the body: Low-density lipoproteins (LDL): LDL cholesterol sometimes is called "bad" cholesterol. A high LDL ... or even death. The higher the level of LDL cholesterol in your blood, the GREATER your chance is ...

  9. A cholesterol-free, high-fat diet suppresses gene expression of cholesterol transporters in murine small intestine

    NARCIS (Netherlands)

    Bosch, van den H.M.; Wit, de N.J.W.; Hooiveld, G.J.E.J.; Vermeulen, H.; Veen, van der J.N.; Houten, S.M.; Kuipers, F.; Müller, M.R.; Meer, van der R.

    2008-01-01

    Transporters present in the epithelium of the small intestine determine the efficiency by which dietary and biliary cholesterol are taken up into the body and thus control whole-body cholesterol balance. Niemann-Pick C1 Like Protein 1 (Npc1l1) transports cholesterol into the enterocyte, whereas ATP-

  10. 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

  11. Cholesterol efflux capacity: An introduction for clinicians.

    Science.gov (United States)

    Anastasius, Malcolm; Kockx, Maaike; Jessup, Wendy; Sullivan, David; Rye, Kerry-Anne; Kritharides, Leonard

    2016-10-01

    Epidemiologic studies have shown an inverse correlation between high-density lipoprotein (HDL) cholesterol (HDL-C) levels and cardiovascular disease outcomes. However, the hypothesis of a causal relationship between HDL-C and cardiovascular disease has been challenged by genetic and clinical studies. Serum cholesterol efflux capacity (CEC) is an important measure of HDL function in humans. Recent large clinical studies have shown a correlation between in vitro CEC and cardiovascular disease prevalence and incidence, which appears to be independent of HDL-C concentration. The present review summarizes recent large clinical studies and introduces important methodological considerations. Further studies are required to standardize and establish the reproducibility of this measure of HDL function and clarify whether modulating CEC will emerge as a useful therapeutic target. PMID:27659883

  12. Cholesterol gallstone disease: the current status of nonsurgical therapy.

    Science.gov (United States)

    Bilhartz, L E

    1988-07-01

    Gallstone disease is a common disease that appears to be related to a Western diet. The underlying pathogenesis is a subtle alteration in the liver such that excessive cholesterol is extracted from the liver cell by bile acids undergoing an enterohepatic recirculation. Gallstone disease progresses through well-defined stages, beginning with a bile supersaturated with cholesterol and proceeding to crystal formation, stone growth, and finally symptoms caused by impaction of a stone in either the cystic duct or the common bile duct. The natural history is that most stones never cause symptoms. Stones that cause symptoms have been present for an average of 12 years. The treatment of truly asymptomatic stones should be observation. Ultrasonography of the right upper quadrant is the gold standard for the diagnosis of stones in the gallbladder. Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for the diagnosis of stones in the common bile duct. Oral cholecystogram (OCG) helps select patients who have noncalcified, floating stones that may be dissolved with bile acids or methyl tertiary butyl ether (MTBE). Therapy with chenodiol has been a disappointment because of a low complete response rate. The ideal candidate for attempted dissolution with chenodiol would be a thin woman with hypercholesterolemia and a small number of symptomatic, small, floating, radiolucent gallstones. Ursodeoxycholic acid (Urso), when it is available, will have all of the attributes of chenodiol and virtually none of the side effects. Rapid dissolution of gallstones with MTBE shows great promise of being a generally available means of dissolving gallstones. Extracorporeal shock wave lithotripsy also shows promise, but its general availability may be limited by the cost of the equipment needed. As of now, the treatment of choice for symptomatic gallstones remains cholecystectomy, unless there is a compelling reason not to operate. PMID:3044106

  13. Smectite alteration

    International Nuclear Information System (INIS)

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  14. Effect of serum, cholesterol and low density lipoprotein on the functionality and structure of lung surfactant films.

    Science.gov (United States)

    Nahak, Prasant; Nag, Kaushik; Hillier, Ashley; Devraj, Ravi; Thompson, David W; Manna, Kausik; Makino, Kimiko; Ohshima, Hiroyuki; Nakahara, Hiromichi; Shibata, Osamu; Panda, Amiya Kumar

    2014-01-01

    Lung surfactant is a complex mixture of lipid and protein, responsible for alveolar stability, becomes dysfunctional due to alteration of its structure and function by leaked serum materials in disease. Serum proteins, cholesterol and low density lipoprotein (LDL) were studied with bovine lipid extract surfactant (BLES) using Langmuir films, and bilayer dispersions using Raman spectroscopy. While small amount of cholesterol (10 wt%) and LDL did not significantly affect the adsorption and surface tension lowering properties of BLES. However serum lipids, whole serum as well as higher amounts of cholesterol, and LDL dramatically altered the surface properties of BLES films, as well as gel-fluid structures formed in such films observed using atomic force microscopy (AFM). Raman-spectroscopic studies revealed that serum proteins, LDL and excess cholesterol had fluidizing effects on BLES bilayers dispersion, monitored from the changes in hydrocarbon vibrational modes during gel-fluid thermal phase transitions. This study clearly suggests that patho-physiological amounts of serum lipids (and not proteins) significantly alter the molecular arrangement of surfactant in films and bilayers, and can be used to model lung disease. PMID:25409691

  15. Viral depletion of VTA BDNF in rats modulates social behavior, consequences of intermittent social defeat stress, and long-term weight regulation

    OpenAIRE

    Fanous, Sanya; Terwilliger, Ernest F; Hammer, Ronald P.; Nikulina, Ella M.

    2011-01-01

    Mesolimbic brain-derived neurotrophic factor (BDNF) is implicated in sustained behavioral changes following chronic social stress, and its depletion may reduce susceptibility to such behavioral alterations. Enhanced mesolimbic BDNF is proposed as pro-depressive and anhedonic, while depleting ventral tegmetal area (VTA) BDNF increases weight by enhancing hedonic eating. Here, we questioned whether depletion of VTA BDNF would alleviate social defeat stress-induced deficits in weight regulation,...

  16. Cholesterol in serum lipoprotein fractions after spaceflight

    Science.gov (United States)

    Leach, Carolyn S.; Johnson, Philip C., Jr.; Krauhs, Jane M.; Cintron, Nitza M.

    1988-01-01

    Results are reported from blood-lipid measurements obtained from 125 Space Shuttle crew members before and after space flight. The data are presented in tables and discussed in detail. The main differences noted between preflight and postflight values are a 12.8-percent decrease in high-density lipoproteins on postflight day 1 and significant decreases in total cholesterol and both high- and low-density lipoproteins later in the 23-day postflight period.

  17. 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....... As ceramide incorporates the lipid backbone common to all sphingolipids, this arrangement may be relevant to the understanding of the molecular organization of lipid rafts....

  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. 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 s...

  20. [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

  1. In Vivo Depletion of T Lymphocytes.

    Science.gov (United States)

    Laky, Karen; Kruisbeek, Ada M

    2016-01-01

    In vivo depletion of T lymphocytes is a means of studying the role of specific T cell populations during defined phases of in vivo immune responses. In this unit, a protocol is provided for injecting monoclonal antibodies (mAbs) into wild-type adult mice. Depletion of the appropriate subset of cells is verified by flow cytometry analysis of lymph node and spleen cell suspensions in pilot experiments. Once conditions have been established, depleted mice can be used to study the impact of T cell subsets on a variety of in vivo immune responses. The depleted condition may be maintained by repeated injections of the monoclonal antibody, or reversed by normal thymopoiesis following discontinuation of antibody administration. PMID:27038463

  2. Polar stratospheric clouds and ozone depletion

    Science.gov (United States)

    Toon, Owen B.; Turco, Richard P.

    1991-01-01

    A review is presented of investigations into the correlation between the depletion of ozone and the formation of polar stratospheric clouds (PSCs). Satellite measurements from Nimbus 7 showed that over the years the depletion from austral spring to austral spring has generally worsened. Approximately 70 percent of the ozone above Antarctica, which equals about 3 percent of the earth's ozone, is lost during September and October. Various hypotheses for ozone depletion are discussed including the theory suggesting that chlorine compounds might be responsible for the ozone hole, whereby chlorine enters the atmosphere as a component of chlorofluorocarbons produced by humans. The three types of PSCs, nitric acid trihydrate, slowly cooling water-ice, and rapidly cooling water-ice clouds act as important components of the Antarctic ozone depletion. It is indicated that destruction of the ozone will be more severe each year for the next few decades, leading to a doubling in area of the Antarctic ozone hole.

  3. Depleted UF6 programmatic environmental impact statement

    International Nuclear Information System (INIS)

    The US Department of Energy has developed a program for long-term management and use of depleted uranium hexafluoride, a product of the uranium enrichment process. As part of this effort, DOE is preparing a Programmatic Environmental Impact Statement (PEIS) for the depleted UF6 management program. This report duplicates the information available at the web site (http://www.ead.anl.gov/web/newduf6) set up as a repository for the PEIS. Options for the web site include: reviewing recent additions or changes to the web site; learning more about depleted UF6 and the PEIS; browsing the PEIS and related documents, or submitting official comments on the PEIS; downloading all or part of the PEIS documents; and adding or deleting one's name from the depleted UF6 mailing list

  4. Ecological considerations of natural and depleted uranium

    International Nuclear Information System (INIS)

    Depleted 238U is a major by-product of the nuclear fuel cycle for which increasing use is being made in counterweights, radiation shielding, and ordnance applications. This paper (1) summarizes the pertinent literature on natural and depleted uranium in the environment, (2) integrates results of a series of ecological studies conducted at Los Alamos Scientific Laboratory (LASL) in New Mexico where 70,000 kg of depleted and natural uranium has been expended to the environment over the past 34 years, and (3) synthesizes the information into an assessment of the ecological consequences of natural and depleted uranium released to the environment by various means. Results of studies of soil, plant, and animal communities exposed to this radiation and chemical environment over a third of a century provide a means of evaluating the behavior and effects of uranium in many contexts

  5. Fully Depleted Charge-Coupled Devices

    International Nuclear Information System (INIS)

    We have developed fully depleted, back-illuminated CCDs that build upon earlier research and development efforts directed towards technology development of silicon-strip detectors used in high-energy-physics experiments. The CCDs are fabricated on the same type of high-resistivity, float-zone-refined silicon that is used for strip detectors. The use of high-resistivity substrates allows for thick depletion regions, on the order of 200-300 um, with corresponding high detection efficiency for near-infrared and soft x-ray photons. We compare the fully depleted CCD to the p-i-n diode upon which it is based, and describe the use of fully depleted CCDs in astronomical and x-ray imaging applications

  6. Effect of black tea intake on blood cholesterol concentrations in individuals with mild hypercholesterolemia: a diet-controlled randomized trial.

    Science.gov (United States)

    Troup, Rasa; Hayes, Jennifer H; Raatz, Susan K; Thyagarajan, Bharat; Khaliq, Waseem; Jacobs, David R; Key, Nigel S; Morawski, Bozena M; Kaiser, Daniel; Bank, Alan J; Gross, Myron

    2015-02-01

    Habitual intake of black tea has been associated with relatively lower serum cholesterol concentrations in observational studies. However, clinical trial results evaluating the effects of black tea on serum cholesterol have been inconsistent. Several factors could explain these mixed results, in particular, uncontrolled confounding caused by lifestyle factors (eg, diet). This diet-controlled clinical trial estimates the effect of black tea flavonoid consumption on cholesterol concentrations in 57 borderline hypercholesterolemic individuals (total cholesterol concentrations between 190 and 260 mg/dL [4.9 and 6.7 mmol/L]). A double-blind, randomized crossover trial was conducted in Minneapolis, MN, from April 2002 through April 2004 in which key conditions were tightly controlled to minimize possible confounding. Participants consumed a controlled low-flavonoid diet plus 5 cups per day of black tea or tea-like placebo during two 4-week treatment periods. The flavonoid-free caffeinated placebo matched the tea in color and taste. Differences in cholesterol concentrations at the end of each treatment period were evaluated via linear mixed models. Differences among those treated with tea vs placebo were 3.43 mg/dL (0.09 mmol/L) (95% CI -7.08 to 13.94) for total cholesterol, -1.02 mg/dL (-0.03 mmol/L) (95% CI -11.34 to 9.30) for low-density lipoprotein cholesterol, 0.58 mg/dL (0.02 mmol/L) (95% CI -2.98 to 4.14) for high-density lipoprotein cholesterol, 15.22 mg/dL (0.17 mmol/L) (95% CI -40.91 to 71.35) for triglycerides, and -0.39 mg/dL (-0.01 mmol/L) (95% CI -11.16 to 10.38) for low-density lipoprotein plus high-density lipoprotein cholesterol fraction. The low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio decreased by -0.1 units (95% CI -0.41 to 0.21). No results were statistically or clinically significant. The intake of 5 cups of black tea per day did not alter the lipid profile of borderline hypercholesterolemic subjects

  7. A theoretical model of atmospheric ozone depletion

    Science.gov (United States)

    Midya, S. K.; Jana, P. K.; Lahiri, T.

    1994-01-01

    A critical study on different ozone depletion and formation processes has been made and following important results are obtained: (i) From analysis it is shown that O3 concentration will decrease very minutely with time for normal atmosphere when [O], [O2] and UV-radiation remain constant. (ii) An empirical equation is established theoretically between the variation of ozone concentration and time. (iii) Special ozone depletion processes are responsible for the dramatic decrease of O3-concentration at Antarctica.

  8. Depleted Uranium and Its Effects on Humans

    Directory of Open Access Journals (Sweden)

    Zdeněk Hon

    2015-04-01

    Full Text Available The article summarizes contemporary scientific knowledge of depleted uranium effects on human health due to its use in military conflicts. The discussion covers cases of minimal risk due to external irradiation resulting from the storage and handling of depleted uranium ammunition and, in contrast, important toxicological and radio-toxicological risks of late effects resulting from the inhalation and ingestion of dust particles produced by the burning of the core of the anti-tank ammunition.

  9. Depleted Uranium and Its Effects on Humans

    OpenAIRE

    Zdeněk Hon; Jan Österreicher; Leoš Navrátil

    2015-01-01

    The article summarizes contemporary scientific knowledge of depleted uranium effects on human health due to its use in military conflicts. The discussion covers cases of minimal risk due to external irradiation resulting from the storage and handling of depleted uranium ammunition and, in contrast, important toxicological and radio-toxicological risks of late effects resulting from the inhalation and ingestion of dust particles produced by the burning of the core of the anti-tank ammunition.

  10. Depleted Bulk Heterojunction Colloidal Quantum Dot Photovoltaics

    KAUST Repository

    Barkhouse, D. Aaron R.

    2011-05-26

    The first solution-processed depleted bulk heterojunction colloidal quantum dot solar cells are presented. The architecture allows for high absorption with full depletion, thereby breaking the photon absorption/carrier extraction compromise inherent in planar devices. A record power conversion of 5.5% under simulated AM 1.5 illumination conditions is reported. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Astragalus polysaccharides lowers plasma cholesterol through mechanisms distinct from statins.

    Directory of Open Access Journals (Sweden)

    Yunjiu Cheng

    Full Text Available To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25 g/kg/d on plasma and liver lipids, fecal bile acids and neutral sterol, cholesterol absorption and synthesis, HMG-CoA reductase activity, and gene and protein expressions in the liver and small intestine was investigated in twenty-four hypercholesterolemia hamsters. Treatment periods lasted for three months. APS significantly lowered plasma total cholesterol by 45.8%, triglycerides by 30%, and low-density lipoprotein-cholesterol by 47.4%, comparable to simvastatin. Further examinations revealed that APS reduced total cholesterol and triglycerides in the liver, increased fecal bile acid and neutral sterol excretion, inhibited cholesterol absorption, and by contrast, increased hepatic cholesterol synthesis and HMG-CoA reductase activity. Plasma total cholesterol or low-density lipoprotein-cholesterol levels were significantly correlated with cholesterol absorption rates. APS up-regulated cholesterol-7α-hydroxylase and LDL-receptor gene expressions. These new findings identify APS as a potential natural cholesterol lowering agent, working through mechanisms distinct from statins.

  12. Development of Monte Carlo depletion code MCDEP

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K. S.; Kim, K. Y.; Lee, J. C.; Ji, S. K. [KAERI, Taejon (Korea, Republic of)

    2003-07-01

    Monte Carlo neutron transport calculation has been used to obtain a reference solution in reactor physics analysis. The typical and widely-used Monte Carlo transport code is MCNP (Monte Carlo N-Particle Transport Code) developed in Los Alamos National Laboratory. The drawbacks of Monte-Carlo transport codes are the lacks of the capacities for the depletion and temperature dependent calculations. In this research we developed MCDEP (Monte Carlo Depletion Code Package) using MCNP with the capacity of the depletion calculation. This code package is the integration of MCNP and depletion module of ORIGEN-2 using the matrix exponential method. This code package enables the automatic MCNP and depletion calculations only with the initial MCNP and MCDEP inputs prepared by users. Depletion chains were simplified for the efficiency of computing time and the treatment of short-lived nuclides without cross section data. The results of MCDEP showed that the reactivity and pin power distributions for the PWR fuel pins and assemblies are consistent with those of CASMO-3 and HELIOS.

  13. Preterm delivery and low maternal serum cholesterol level: Any correlation?

    Directory of Open Access Journals (Sweden)

    Ayodeji A Oluwole

    2014-01-01

    Full Text Available Background: The study assessed whether low maternal serum cholesterol during early pregnancy is associated with preterm delivery. Patients and Methods: It was a prospective observational cohort study involving pregnant women at gestational age of 14-20 weeks over a period of 12 months. Blood samples were obtained to measure total serum cholesterol concentrations and the sera were then analysed enzymatically by the cholesterol oxidase: p-aminophenazone (CHOD PAP method. 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. Conclusion: Low maternal serum cholesterol (hypocholesterolaemia is associated with preterm delivery. Optimal maternal serum cholesterol during pregnancy may have merit, therefore pregnant women should be encouraged to follow a healthy, balanced diet.

  14. 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.

  15. Radiative characteristics of depleted uranium bomb and it is protection

    International Nuclear Information System (INIS)

    Based on the developing process of depleted uranium bombs described in the first part, the radiative characteristics and mechanism of depleted uranium bombs are analyzed emphatically. The deeper discussion on protection of depleted uranium bombs is proceeded

  16. 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.

  17. Mitotic spindle defects and chromosome mis-segregation induced by LDL/cholesterol-implications for Niemann-Pick C1, Alzheimer's disease, and atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Antoneta Granic

    Full Text Available Elevated low-density lipoprotein (LDL-cholesterol is a risk factor for both Alzheimer's disease (AD and Atherosclerosis (CVD, suggesting a common lipid-sensitive step in their pathogenesis. Previous results show that AD and CVD also share a cell cycle defect: chromosome instability and up to 30% aneuploidy-in neurons and other cells in AD and in smooth muscle cells in atherosclerotic plaques in CVD. Indeed, specific degeneration of aneuploid neurons accounts for 90% of neuronal loss in AD brain, indicating that aneuploidy underlies AD neurodegeneration. Cell/mouse models of AD develop similar aneuploidy through amyloid-beta (Aß inhibition of specific microtubule motors and consequent disruption of mitotic spindles. Here we tested the hypothesis that, like upregulated Aß, elevated LDL/cholesterol and altered intracellular cholesterol homeostasis also causes chromosomal instability. Specifically we found that: 1 high dietary cholesterol induces aneuploidy in mice, satisfying the hypothesis' first prediction, 2 Niemann-Pick C1 patients accumulate aneuploid fibroblasts, neurons, and glia, demonstrating a similar aneugenic effect of intracellular cholesterol accumulation in humans 3 oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL, induce chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors, indicating that LDL/cholesterol directly affects the cell cycle, 4 LDL-induced aneuploidy requires the LDL receptor, but not Aß, showing that LDL works differently than Aß, with the same end result, 5 cholesterol treatment disrupts the structure of the mitotic spindle, providing a cell biological mechanism for its aneugenic activity, and 6 ethanol or calcium chelation attenuates lipoprotein-induced chromosome mis-segregation, providing molecular insights into cholesterol's aneugenic mechanism, specifically through its rigidifying effect on the cell membrane, and potentially explaining why ethanol

  18. Exposure to polymers reverses inhibition of pulmonary surfactant by serum, meconium, or cholesterol in the captive bubble surfactometer.

    Science.gov (United States)

    López-Rodríguez, Elena; Ospina, Olga Lucía; Echaide, Mercedes; Taeusch, H William; Pérez-Gil, Jesús

    2012-10-01

    Dysfunction of pulmonary surfactant in the lungs is associated with respiratory pathologies such as acute respiratory distress syndrome or meconium aspiration syndrome. Serum, cholesterol, and meconium have been described as inhibitory agents of surfactant's interfacial activity once these substances appear in alveolar spaces during lung injury and inflammation. The deleterious action of these agents has been only partly evaluated under physiologically relevant conditions. We have optimized a protocol to assess surfactant inhibition by serum, cholesterol, or meconium in the captive bubble surfactometer. Specific measures of surface activity before and after native surfactant was exposed to inhibitors included i), film formation, ii), readsorption of material from surface-associated reservoirs, and iii), interfacial film dynamics during compression-expansion cycling. Results show that serum creates a steric barrier that impedes surfactant reaching the interface. A mechanical perturbation of this barrier allows native surfactant to compete efficiently with serum to form a highly surface-active film. Exposure of native surfactant to cholesterol or meconium, on the other hand, modifies the compressibility of surfactant films though optimal compressibility properties recover on repetitive compression-expansion cycling. Addition of polymers like dextran or hyaluronic acid to surfactant fully reverses inhibition by serum. These polymers also prevent surfactant inhibition by cholesterol or meconium, suggesting that the protective action of polymers goes beyond the mere enhancement of interfacial adsorption as described by depletion force theories. PMID:23062337

  19. Diet and Age Interactions with Regards to Cholesterol Regulation and Brain Pathogenesis

    Directory of Open Access Journals (Sweden)

    Romina M. Uranga

    2010-01-01

    Full Text Available Cholesterol is an essential molecule for brain homeostasis; yet, hypercholesterolemia and its numerous complications are believed to play a role in promoting multiple aspects of brain pathogenesis. An ever increasing number of individuals in modern Western Society are regularly consuming diets high in fat which promote the development of hypercholesterolemia. Additionally, modern societies are becoming increasingly aged, causing a collision between increased hypercholesterolemia and increased aging, which will likely lead to the development of increased pathological conditions due to hypercholesterolemia, thereby promoting deleterious neurochemical and behavioral changes in the brain. Lastly, while beneficial in controlling cholesterol levels, the long-term use of statins itself may potentially promote adverse effects on brain homeostasis, although specifics on this remain largely unknown. This review will focus on linking the current understanding of diet-induced hypercholesterolemia (as well as statin use to the development of oxidative stress, neurochemical alterations, and cognitive disturbances in the aging brain.

  20. Cholesterol and iron availability in yolk of laying hens feed with annatto ( Bixa orellana).

    Science.gov (United States)

    Harder, M N C; Canniatti-Brazaca, S G; Coelho, A A D; Savino, V J M; Franco, C F O

    2007-03-01

    Pigmented egg yolks are more attractive. Popular culture treats annatto as a powerful anticholesterolemic agent, besides being widely used in the form of industry pigment. This work evaluated the effects of the addition of annatto (Bixa orellana L.) in the feed of hens, verifying a possible alteration of cholesterol in the yolks, content of carotenes, and iron and available iron, over time. One hundred and twenty-five hens divided in control (0% - T1) and four annatto-added treatments (0.5% - T2; 1.0% - T3; 1.5% - T4, and 2.0% - T5) were used. Eggs were collected at 23, 25, 27, 29 and 30 weeks. The animals were randomly separated into five groups of five animals each. The cholesterol was measured by the colorimetric method, vitamin A (β and α carotene) by spectrophotometry, total iron by atomic absorption spectrophotometry, and dialysable iron by dialysis. Tukey's test was used at the 5% level for comparison of the averages. Regarding cholesterol, treatments T2 and T3 did not differ significantly. However, other treatments differed ( P ≤ 0.05) from the control, decreasing the cholesterol level as the percentage of annatto in the feed increased. In time, there was a significant increase ( P ≤ 0.05). For β and α carotene, T5 presented statistically higher values than the others ( P ≤ 0.05). With regard to total iron, T5 had higher values than the others. Dialysable iron was also higher, probably due to the increase in carotenes. Thus, we can conclude that the use of annatto in the feed of layer hens is useful, as it provokes the reduction of cholesterol and promotes an increase in the content of iron and carotenes in eggs. PMID:22444346

  1. 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.

  2. Depletion sensitivity predicts unhealthy snack purchases.

    Science.gov (United States)

    Salmon, Stefanie J; Adriaanse, Marieke A; Fennis, Bob M; De Vet, Emely; De Ridder, Denise T D

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose weight on snack purchase behavior were explored. Participants included in the study were instructed to report every snack they bought over the course of one week. The dependent variables were the number of healthy and unhealthy snacks purchased. The results of the present study demonstrate that depletion sensitivity predicts the amount of unhealthy (but not healthy) snacks bought. The more sensitive people are to depletion, the more unhealthy snacks they buy. Moreover, there was some tentative evidence that this relation is more pronounced for people with a weak as opposed to a strong goal to lose weight, suggesting that a strong goal to lose weight may function as a motivational buffer against self-control failures. All in all, these findings provide evidence for the external validity of depletion sensitivity and the relevance of this construct in the domain of eating behavior. PMID:26321417

  3. The New MCNP6 Depletion Capability

    Energy Technology Data Exchange (ETDEWEB)

    Fensin, Michael Lorne [Los Alamos National Laboratory; James, Michael R. [Los Alamos National Laboratory; Hendricks, John S. [Los Alamos National Laboratory; Goorley, John T. [Los Alamos National Laboratory

    2012-06-19

    The first MCNP based inline Monte Carlo depletion capability was officially released from the Radiation Safety Information and Computational Center as MCNPX 2.6.0. Both the MCNP5 and MCNPX codes have historically provided a successful combinatorial geometry based, continuous energy, Monte Carlo radiation transport solution for advanced reactor modeling and simulation. However, due to separate development pathways, useful simulation capabilities were dispersed between both codes and not unified in a single technology. MCNP6, the next evolution in the MCNP suite of codes, now combines the capability of both simulation tools, as well as providing new advanced technology, in a single radiation transport code. We describe here the new capabilities of the MCNP6 depletion code dating from the official RSICC release MCNPX 2.6.0, reported previously, to the now current state of MCNP6. NEA/OECD benchmark results are also reported. The MCNP6 depletion capability enhancements beyond MCNPX 2.6.0 reported here include: (1) new performance enhancing parallel architecture that implements both shared and distributed memory constructs; (2) enhanced memory management that maximizes calculation fidelity; and (3) improved burnup physics for better nuclide prediction. MCNP6 depletion enables complete, relatively easy-to-use depletion calculations in a single Monte Carlo code. The enhancements described here help provide a powerful capability as well as dictate a path forward for future development to improve the usefulness of the technology.

  4. Climate Change and Oil Depletion

    International Nuclear Information System (INIS)

    Primary energy sources have progressively displaced each other and shared the supply in terms that can historically be described by a model proposed by Cesare Marchetti as a generalization of the Fisher and Pry law. So wood, coal, oil and natural gas have displaced or are displacing each other, each one following a logistic evolution until a maximum share is attained, afterwards receding in a symmetrically similar way, provided there is no exhaustion of the respective resource base, each one completing its own life cycle. On the other hand, the persistent growth of the total energy demand implies that the total amount of each one of the successive primary energy sources, required to complete its life cycle, is growing as time lapses. So it is realized that coal resources are much larger than its total life cycle demand. The same is not the case of oil, whose resource base (estimate 2000 Gb) may be smaller than the integrated prospective demand unless this starts declining steadily in the near future. However, if the rate of growth of total energy demand is persists, the amount of natural gas required to complete a similar life cycle will likely exceed its actual resource base. One faces therefore two problems: the constraint on oil availability right now and a likely, even more severe, constraint on natural gas in about twenty years time. Combustion of fossil fuels always produces CO2 emissions as well as nitrogen oxides. With the exception of natural gas, all other fuels also produce, to a variable extent, particulate matter (aerosols) and sulfur oxides. The permanent alteration of the chemical composition of the atmosphere as a result of all these emissions may affect the biogeochemical balance of the climate system. Such emissions produce recognized impacts of some sort at local and regional levels, either temporary or permanent. Whether actual impacts can be global and permanent is still under dispute; but the observed steady and simultaneous increase of the CO

  5. Scavenger receptor BI: a multi-purpose player in cholesterol and steroid metabolism.

    Science.gov (United States)

    Hoekstra, Menno; Van Berkel, Theo-Jc; Van Eck, Miranda

    2010-12-21

    Scavenger receptor class B type I (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepatocytes, which identifies SR-BI as a multi-purpose player in lipid uptake from the blood circulation into hepatocytes in mice. In adrenocortical cells, SR-BI mediates the selective uptake of HDL-cholesteryl esters, which is efficiently coupled to the synthesis of glucocorticoids (i.e. corticosterone). SR-BI knockout mice suffer from adrenal glucocorticoid insufficiency, which suggests that functional SR-BI protein is necessary for optimal adrenal steroidogenesis in mice. SR-BI in macrophages plays a dual role in cholesterol metabolism as it is able to take up cholesterol associated with HDL and apoB-containing lipoproteins and can possibly facilitate cholesterol efflux to HDL. Absence of SR-BI is associated with thrombocytopenia and altered thrombosis susceptibility, which suggests a novel role for SR-BI in regulating platelet number and function in mice. Transgenic expression of cholesteryl ester transfer protein in humanized SR-BI knockout mice normalizes hepatic delivery of HDL-cholesteryl esters. However, other pathologies associated with SR-BI deficiency, i.e. increased atherosclerosis susceptibility, adrenal glucocorticoid insufficiency, and impaired platelet function are not normalized, which suggests an important role for SR-BI in cholesterol and steroid metabolism in man. In conclusion, generation of SR-BI knockout mice has significantly contributed to our knowledge of the physiological role of SR-BI. Studies using these mice have identified SR-BI as a

  6. Cholesterol Metabolism and Prostate Cancer Lethality.

    Science.gov (United States)

    Stopsack, Konrad H; Gerke, Travis A; Sinnott, Jennifer A; Penney, Kathryn L; Tyekucheva, Svitlana; Sesso, Howard D; Andersson, Swen-Olof; Andrén, Ove; Cerhan, James R; Giovannucci, Edward L; Mucci, Lorelei A; Rider, Jennifer R

    2016-08-15

    Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease. Cancer Res; 76(16); 4785-90. ©2016 AACR.

  7. Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice.

    Directory of Open Access Journals (Sweden)

    Pin Yue

    Full Text Available CD36 facilitates oxidized low density lipoprotein uptake and is implicated in development of atherosclerotic lesions. CD36 also binds unmodified high and very low density lipoproteins (HDL, VLDL but its role in the metabolism of these particles is unclear. Several polymorphisms in the CD36 gene were recently shown to associate with serum HDL cholesterol. To gain insight into potential mechanisms for these associations we examined HDL metabolism in CD36 null (CD36(-/- mice. Feeding CD36(-/- mice a high cholesterol diet significantly increased serum HDL, cholesterol and phospholipids, as compared to wild type mice. HDL apolipoproteins apoA-I and apoA-IV were increased and shifted to higher density HDL fractions suggesting altered particle maturation. Clearance of dual-labeled HDL was unchanged in CD36(-/- mice and cholesterol uptake from HDL or LDL by isolated CD36(-/- hepatocytes was unaltered. However, CD36(-/- hepatocytes had higher cholesterol and phospholipid efflux rates. In addition, expression and secretion of apoA-I and apoA-IV were increased reflecting enhanced PXR. Similar to hepatocytes, cholesterol and phospholipid efflux were enhanced in CD36(-/- macrophages without changes in protein levels of ABCA1, ABCG1 or SR-B1. However, biotinylation assays showed increased surface ABCA1 localization in CD36(-/- cells. In conclusion, CD36 influences reverse cholesterol transport and hepatic ApoA-I production. Both pathways are enhanced in CD36 deficiency, increasing HDL concentrations, which suggests the potential benefit of CD36 inhibition.

  8. Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation.

    Science.gov (United States)

    Afonso, Milessa Silva; Lavrador, Maria Silvia Ferrari; Koike, Marcia Kiyomi; Cintra, Dennys Esper; Ferreira, Fabiana Dias; Nunes, Valeria Sutti; Castilho, Gabriela; Gioielli, Luiz Antonio; Paula Bombo, Renata; Catanozi, Sergio; Caldini, Elia Garcia; Damaceno-Rodrigues, Nilsa Regina; Passarelli, Marisa; Nakandakare, Edna Regina; Lottenberg, Ana Maria

    2016-06-01

    Interesterified fats are currently being used to replace trans fatty acids. However, their impact on biological pathways involved in the atherosclerosis development was not investigated. Weaning male LDLr-KO mice were fed for 16weeks on a high-fat diet (40% energy as fat) containing polyunsaturated (PUFA), TRANS, palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR) or stearic interesterified (STEAR INTER). Plasma lipids, lipoprotein profile, arterial lesion area, macrophage infiltration, collagen content and inflammatory response modulation were determined. Macrophage cholesterol efflux and the arterial expression of cholesterol uptake and efflux receptors were also performed. The interesterification process did not alter plasma lipid concentrations. Although PALM INTER did not increase plasma cholesterol concentration as much as TRANS, the cholesterol enrichment in the LDL particle was similar in both groups. Moreover, PALM INTER induced the highest IL-1β, MCP-1 and IL-6 secretion from peritoneal macrophages as compared to others. This inflammatory response elicited by PALM INTER was confirmed in arterial wall, as compared to PALM. These deleterious effects of PALM INTER culminate in higher atherosclerotic lesion, macrophage infiltration and collagen content than PALM, STEAR, STEAR INTER and PUFA. These events can partially be attributed to a macrophage cholesterol accumulation, promoted by apoAI and HDL2-mediated cholesterol efflux impairment and increased Olr-1 and decreased Abca1 and Nr1h3 expressions in the arterial wall. Interesterified fats containing palmitic acid induce atherosclerosis development by promoting cholesterol accumulation in LDL particles and macrophagic cells, activating the inflammatory process in LDLr-KO mice.

  9. Experimental depletion of different renal interstitial cell populations

    International Nuclear Information System (INIS)

    To define different populations of renal interstitial cells and investigate some aspects of their function, we studied the kidneys of normal rats and rats with hereditary diabetes insipidus (DI, Brattleboro) after experimental manipulations expected to alter the number of interstitial cells. DI rats showed an almost complete loss of interstitial cells in their renal papillae after treatment with a high dose of vasopressin. In spite of the lack of interstitial cells, the animals concentrated their urine to the same extent as vasopressin-treated normal rats, indicating that the renomedullary interstitial cells do not have an important function in concentrating the urine. The interstitial cells returned nearly to normal within 1 week off vasopressin treatment, suggesting a rapid turnover rate of these cells. To further distinguish different populations of interstitial cells, we studied the distribution of class II MHC antigen expression in the kidneys of normal and bone-marrow depleted Wistar rats. Normal rats had abundant class II antigen-positive interstitial cells in the renal cortex and outer medulla, but not in the inner medulla (papilla). Six days after 1000 rad whole body irradiation, the stainable cells were almost completely lost, but electron microscopic morphometry showed a virtually unchanged volume density of interstitial cells in the cortex and outer medulla, as well as the inner medulla. Thus, irradiation abolished the expression of the class II antigen but caused no significant depletion of interstitial cells

  10. 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.

  11. Depleted uranium and the Gulf War syndrome

    International Nuclear Information System (INIS)

    Some military personnel involved in the 1991Gulf War have complained of continuing stress-like symptoms for which no obvious cause has been found. These symptoms have at times been attributed to the use of depleted uranium (DU) in shell casings which are believed to have caused toxic effects. Depleted uranium is natural uranium which is depleted in the rarer U-235 isotope. It is a heavy metal and in common with other heavy metals is chemically toxic. It is also slightly radioactive and could give rise to a radiological hazard if dispersed in finely divided form so that it was inhaled. In response to concerns, the possible effects of DU have been extensively studied along with other possible contributors to Gulf War sickness. This article looks at the results of some of the research that has been done on DU. (author)

  12. Ozone depletion and chlorine loading potentials

    Science.gov (United States)

    Pyle, John A.; Wuebbles, Donald J.; Solomon, Susan; Zvenigorodsky, Sergei; Connell, Peter; Ko, Malcolm K. W.; Fisher, Donald A.; Stordal, Frode; Weisenstein, Debra

    1991-01-01

    The recognition of the roles of chlorine and bromine compounds in ozone depletion has led to the regulation or their source gases. Some source gases are expected to be more damaging to the ozone layer than others, so that scientific guidance regarding their relative impacts is needed for regulatory purposes. Parameters used for this purpose include the steady-state and time-dependent chlorine loading potential (CLP) and the ozone depletion potential (ODP). Chlorine loading potentials depend upon the estimated value and accuracy of atmospheric lifetimes and are subject to significant (approximately 20-50 percent) uncertainties for many gases. Ozone depletion potentials depend on the same factors, as well as the evaluation of the release of reactive chlorine and bromine from each source gas and corresponding ozone destruction within the stratosphere.

  13. Molten-Salt Depleted-Uranium Reactor

    CERN Document Server

    Dong, Bao-Guo; Gu, Ji-Yuan

    2015-01-01

    The supercritical, reactor core melting and nuclear fuel leaking accidents have troubled fission reactors for decades, and greatly limit their extensive applications. Now these troubles are still open. Here we first show a possible perfect reactor, Molten-Salt Depleted-Uranium Reactor which is no above accident trouble. We found this reactor could be realized in practical applications in terms of all of the scientific principle, principle of operation, technology, and engineering. Our results demonstrate how these reactors can possess and realize extraordinary excellent characteristics, no prompt critical, long-term safe and stable operation with negative feedback, closed uranium-plutonium cycle chain within the vessel, normal operation only with depleted-uranium, and depleted-uranium high burnup in reality, to realize with fission nuclear energy sufficiently satisfying humanity long-term energy resource needs, as well as thoroughly solve the challenges of nuclear criticality safety, uranium resource insuffic...

  14. Plasmonic nanoprobes for stimulated emission depletion microscopy

    CERN Document Server

    Cortes, Emiliano; Sinclair, Hugo G; Guldbrand, Stina; Peveler, William J; Davies, Timothy; Parrinello, Simona; Görlitz, Frederik; Dunsby, Chris; Neil, Mark A A; Sivan, Yonatan; Parkin, Ivan P; French, Paul M; Maier, Stefan A

    2016-01-01

    Plasmonic nanoparticles influence the absorption and emission processes of nearby emitters due to local enhancements of the illuminating radiation and the photonic density of states. Here, we use the plasmon resonance of metal nanoparticles in order to enhance the stimulated depletion of excited molecules for super-resolved microscopy. We demonstrate stimulated emission depletion (STED) microscopy with gold nanorods with a long axis of only 26 nm and a width of 8 nm that provide an enhancement of the resolution compared to fluorescent-only probes without plasmonic components irradiated with the same depletion power. These novel nanoparticle-assisted STED probes represent a ~2x10^3 reduction in probe volume compared to previously used nanoparticles and we demonstrate their application to the first plasmon-assisted STED cellular imaging. We also discuss their current limitations.

  15. Influence of infant and juvenile diets on serum cholesterol, lipoprotein cholesterol, and apolipoprotein concentrations in juvenile baboons (Papio sp.).

    Science.gov (United States)

    Mott, G E; McMahan, C A; Kelley, J L; Farley, C M; McGill, H C

    1982-11-01

    The long-term effects of infant diet (breast milk or formula containing 2, 30, or 60 mg/dl cholesterol) and subsequent dietary cholesterol (1 mg/kcal) and fat (saturated or unsaturated) on serum lipid and apolipoprotein concentrations were estimated using 82 juvenile baboons 4-6 years of age. A significant interaction of infant diet (breast vs formula) with type of fat (saturated vs unsaturated) at 4-6 years of age was observed on HDL cholesterol and apolipoprotein A-I (apoA-I) concentrations. That is, animals breast-fed as infants had higher HDL cholesterol and apoA-I concentrations when fed unsaturated fat from weaning to 4-6 years of age than those fed saturated fat (77 vs 68 mg/dl). In contrast, animals fed formulas in infancy followed by a diet containing unsaturated fat had lower HDL cholesterol and apoA-I concentrations at 4-6 years of age than did those fed saturated fat (67 vs 78 mg/dl). However, breast feeding or feeding formulas containing various levels of cholesterol for 3 months during infancy did not result in statistically significant differences in total serum cholesterol, VLDL + LDL cholesterol and apolipoprotein B (apoB) concentrations. Dietary cholesterol after infancy significantly increased serum total cholesterol, VLDL + LDL and HDL cholesterol, apoA-I and apoB concentrations. All of these response variables also were higher in animals fed saturated fat compared to those fed unsaturated fat on the same level of cholesterol. At 4-6 years of age, regardless of diet, females had significantly higher serum VLDL + LDL cholesterol (57 vs 43 mg/dl) and apoB concentrations (39 vs 30 mg/dl) than did males.

  16. 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.

  17. 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

  18. 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...

  19. Department of Energy depleted uranium recycle

    International Nuclear Information System (INIS)

    With its strategic supply of depleted uranium, the Department of Energy is studying reuse of the material in nuclear radiation shields, military hardware, and commercial applications. the study is expected to warrant a more detailed uranium recycle plan which would include consideration of a demonstration program and a program implementation decision. Such a program, if implemented, would become the largest nuclear material recycle program in the history of the Department of Energy. The bulk of the current inventory of depleted uranium is stored in 14-ton cylinders in the form of solid uranium hexafluoride (UF6). The radioactive 235U content has been reduced to a concentration of 0.2% to 0.4%. Present estimates indicate there are about 55,000 UF6-filled cylinders in inventory and planned operations will provide another 2,500 cylinders of depleted uranium each year. The United States government, under the auspices of the Department of Energy, considers the depleted uranium a highly-refined strategic resource of significant value. A possible utilization of a large portion of the depleted uranium inventory is as radiation shielding for spent reactor fuels and high-level radioactive waste. To this end, the Department of Energy study to-date has included a preliminary technical review to ascertain DOE chemical forms useful for commercial products. The presentation summarized the information including preliminary cost estimates. The status of commercial uranium processing is discussed. With a shrinking market, the number of chemical conversion and fabrication plants is reduced; however, the commercial capability does exist for chemical conversion of the UF6 to the metal form and for the fabrication of uranium radiation shields and other uranium products. Department of Energy facilities no longer possess a capability for depleted uranium chemical conversion

  20. Gammaspectrometric determination of depleted uranium in soil

    International Nuclear Information System (INIS)

    Full text: Three years of monitoring the content of natural radionuclides as well as radionuclides of artificial origin in all samples in the south part of the Republic of Serbia and Montenegro indicated that there was widespread, low-level contamination by depleted uranium at this region. High activity of depleted uranium was found in the soil samples taken at the points where the penetrators were found. We used high resolution gamma spectrometry measurements, because of their simplicity and accuracy. Aims of the control were to asses the increase of radioactivity above the natural levels in the immediate and near vicinity of the bomb craters, to asses the corresponding effect of changed natural radioactivity on the health of the population living in these places and finding unexploded depleted uranium bullets. The collected soil samples were cleaned of plants and stones, dried at 105 deg. C - 110 deg. C till constant weight for 24-48 h. After this, the samples were ground, sieved, and measure in cylindrical geometry. Gamma activity was determined by gamma spectrometry measurements using HP Ge detector (ORTEC), with relative efficiency of 25% and energy resolution of 1.85 keV (1332.5 keV 60Co). The analyser system conducts a peak search, energy assignment, quantification and nuclide identification in acquired spectra. Time of measurement varied from 60000 s to 250000 s. Depleted uranium was found in the soil samples from Vranje region and cape Arza (Montenegro). There are four fenced areas in Vranje region (Pljackovica, Bratoselce, Borovac and Reljan) and one in the Montenegro (cape Arza) where we have found depleted uranium penetrators. The 238U and 235U specific activities and their isotopic composition correspond to depleted uranium (238U/235U ratio from 35 to 77). (author)

  1. Apoprotein E genotype and the response of serum cholesterol to dietary fat, cholesterol and cafestol

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Ordovas, J.M.; Pedro-Botet, J.; Katan, M.B.

    2001-01-01

    Previous studies on the effect of apoprotein E (APOE) polymorphism on the response of serum lipids to diet showed inconsistent results. We therefore studied the effect of apoprotein E polymorphism on responses of serum cholesterol and lipoproteins to various dietary treatments. We combined data on r

  2. 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 ...

  3. Fasting Blood Glucose and Lipid Profile Alterations following Twelve-Month Androgen Deprivation Therapy in Men with Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Hasan S. Sağlam

    2012-01-01

    Full Text Available Purpose. In this retrospective study, we aimed to investigate the effects of androgen deprivation therapy (ADT on blood glucose and blood cholesterol levels over a 12-month period. Materials and Methods. Between January 2010 and June 2012, the data of 44 patients with prostate cancer who were receiving ADT were collected from a hospital database. Patients with additional malignancy or diabetes and those who had been prescribed and were currently taking cholesterol-lowering medication were excluded from the study. Data (including fasting blood glucose levels and a cholesterol profile were collected and analysed statistically. A value <0.05 was considered statistically significant. Results. Twelve months after the initiation of ADT, fasting blood glucose (FBG, total cholesterol (TC, low-density lipoprotein (LDL cholesterol, high-density lipoprotein (HDL cholesterol, and triglyceride (TG levels changed. FBG, TC, LDL cholesterol, and TG increased significantly (, 0.000, 0.000, and 0.000, resp., while HDL cholesterol decreased (. Conclusion. ADT may increase FBG, TC, LDL cholesterol, and TG but decrease HDL cholesterol by the end of a year of treatment. Therefore, close followup may be needed as a consequence of one-year ADT regarding metabolic alterations.

  4. The Chemistry and Toxicology of Depleted Uranium

    OpenAIRE

    Katz, Sidney A.

    2014-01-01

    Natural uranium is comprised of three radioactive isotopes: 238U, 235U, and 234U. Depleted uranium (DU) is a byproduct of the processes for the enrichment of the naturally occurring 235U isotope. The world wide stock pile contains some 1½ million tons of depleted uranium. Some of it has been used to dilute weapons grade uranium (~90% 235U) down to reactor grade uranium (~5% 235U), and some of it has been used for heavy tank armor and for the fabrication of armor-piercing bullets and missiles....

  5. Toxicological issues after depleted uranium weapons attacked

    International Nuclear Information System (INIS)

    Depleted Uranium (DU) is a byproduct of the uranium enrichment for producing nuclear reactor or nuclear weapon. DU is used in the military as an armor-piercing projectile due to its hardness, strength, and density. A lot of DU weapons were fired in the Gulf War, and bring about critical environmental and internal contamination. Therefore, DU becomes suddenly a hot issue. Some toxicological problems after DU weapons attacked have been reviewed, which include features of internal DU contamination. Hazard of wound contamination and inhalation with insoluble uranium, and other urgent toxicological issues. The healthy effects of implanted with depleted uranium pellets were illustrated in particular

  6. 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...

  7. 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...

  8. 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

  9. 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

  10. 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.

  11. Cholesterol granuloma of the paratesticular tissue: A case report

    Science.gov (United States)

    Unal, Dursun; Kilic, Metin; Oner, Sedat; Erkinuresin, Taskın; Demirbas, Murat; Coban, Soner; Aydos, Mustafa Murat

    2015-01-01

    A 38-year-old man was admitted to our clinic with an enlarging right scrotal mass that had been present for 7 years. Right radical inguinal orchiectomy was performed and a histopathological diagnosis confirmed a very rare case of cholesterol granuloma of the paratesticular tissue. It can be very difficult to preoperatively distinguish testicular tumours from cholesterol granulomas of the testis or epididymis. Cholesterol granuloma should be kept in mind in patients with large and non-tender scrotal masses. PMID:26225185

  12. Development of alimentary cholesterol in the plasma and the plasmatic lipoproteins in man, after ingestion of a meal containing octa-deuterated cholesterol; Devenir du cholesterol alimentaire dans le plasma et les lipoproteines plasmatiques chez l`homme, apres ingestion d`un repas contenant du cholesterol octa-deutere

    Energy Technology Data Exchange (ETDEWEB)

    Becue, T.; Ferezou, J.; Simon, G. [Paris-11 Univ., 91 - Orsay (France); Bernard, P.M.; Portugal, H. [Hopital Sainte-Marguerite, 13 - Marseille (France); Dubois, C.; Lairon, D.

    1994-12-31

    Cholesterol absorbed after a test-meal has two origins with man: the biliary cholesterol and the alimentary cholesterol. In order to understand the mechanism of the modification of cholesterol intestinal absorption by oat bran, the alimentary cholesterol has been labelled with octa-deuterated cholesterol, in test-diets. The kinetics of D-cholesterol in plasma and chylomicrons is described. 1 fig., 6 refs.

  13. 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.

  14. 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.

  15. Reproductive effects of di(2-ethylhexyl)phthalate in immature male rats and its relation to cholesterol, testosterone, and thyroxin levels.

    Science.gov (United States)

    Botelho, Giuliana G K; Golin, Munisa; Bufalo, Aedra C; Morais, Rosana N; Dalsenter, Paulo R; Martino-Andrade, Anderson J

    2009-11-01

    Phthalates are chemicals employed in several industrial products and there is a growing body of evidence demonstrating that they induce numerous adverse effects on the reproductive system. This study was carried out to assess possible alterations induced by the plasticizer di(2-ethylhexyl phthalate (DEHP) on cholesterol, testosterone, and thyroxine (total T4) levels, as well as to discuss the significance of these data in global changes observed in the reproductive tract of pubertal animals. Wistar rats aged 21 days received DEHP orally at 0, 250, 500, and 750 mg/kg/day for 30 days and were examined for different reproductive endpoints. At the end of the treatment, significant decreases in relative weight of testosterone-dependent organs, delayed preputial separation, and low serum testosterone were observed at the highest DEHP dose. The plot of the relationship between DEHP dose and serum cholesterol revealed a biphasic effect. The concentration of cholesterol in serum was significantly reduced at 250 mg/kg/day DEHP but returned to control values at 750 mg/kg/day. Cholesterol levels measured in testicular tissue increased with DEHP treatment. Serum T4 levels were not affected by DEHP at any dose, indicating the absence of a link between total thyroxin concentration and phthalate effects on cholesterol levels. Taken together these results indicate that effects observed in serum and testicular cholesterol levels may reflect distinct effects of DEHP on cholesterol synthesis and usage. These results confirm and extend previously reported findings showing that alterations in cholesterol balance may play a role in the suppression of steroidogenesis induced by DEHP in rats. PMID:19330368

  16. 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

  17. 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.

  18. Transfer of cholesterol from macrophages to lymphocytes in culture.

    Science.gov (United States)

    de Bittencourt Júnior, P I; Curi, R

    1998-02-01

    A major feature of macrophage metabolism is its capacity to produce and export cholesterol. Several reports have shown that the manipulation of lymphocyte cholesterol content elicits important changes in lymphocyte proliferation. These findings lead to an inquiry as to whether macrophage-derived cholesterol released into the lymphocyte surroundings may be transferred to the latter thus affecting lymphocyte function. In this study, cholesterol transfer from macrophages to lymphocytes was examined in vitro using rat cells in culture. The findings indicate that there may be a significant transfer of cholesterol from [4-14C]cholesterol labeled resident peritoneal macrophages to mesenteric lymph node resting lymphocytes (up to 173.9 +/- 2.7 pmol/10(7) lymphocytes/10(7) macrophages when co-cultivated for 48 h), in a lipoprotein-dependent manner. This represents the mass transfer of ca. 17 nmoles of cholesterol molecules per 10(7) lymphocytes from 10(7) macrophages (calculated on the basis of specific radioactivity incorporated into macrophages after the pre-labelling period), which suggests that macrophages are capable of replacing the whole lymphocyte cholesterol pool every 21 h. Moreover, an 111%-increase in the total cholesterol content of lymphocytes was found after co-cultivation with macrophages for 48 h. When compared to peritoneal cells, monocytes/macrophages obtained from circulating blood leukocytes presented a much higher cholesterol transfer capacity to lymphocytes (3.06 +/- 0.10 nmol/10(7) lymphocytes/10(7) macrophages co-cultivated for 24 h). Interestingly, inflammatory macrophages dramatically reduced their cholesterol transfer ability (by up to 91%, as compared to resident macrophages). Cholesterol transfer may involve a humoral influence, since it is not only observed when cells are co-cultivated in a single-well chamber system (cells in direct contact), but also in a two-compartment system (where cells can communicate but not by direct contact). Co

  19. 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

  20. 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.

  1. Cholesterol and Copper Affect Learning and Memory in the Rabbit

    Directory of Open Access Journals (Sweden)

    Bernard G. Schreurs

    2013-01-01

    Full Text Available A rabbit model of Alzheimer’s disease based on feeding a cholesterol diet for eight weeks shows sixteen hallmarks of the disease including beta amyloid accumulation and learning and memory changes. Although we have shown that feeding 2% cholesterol and adding copper to the drinking water can retard learning, other studies have shown that feeding dietary cholesterol before learning can improve acquisition and feeding cholesterol after learning can degrade long-term memory. We explore the development of this model, the issues surrounding the role of copper, and the particular contributions of the late D. Larry Sparks.

  2. 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

  3. Retracted: Advances in the physiological and pathological implications of cholesterol.

    Science.gov (United States)

    Cortes, Victor A; Busso, Dolores; Mardones, Pablo; Maiz, Alberto; Arteaga, Antonio; Nervi, Flavio; Rigotti, Attilio

    2013-11-01

    Cholesterol has evolved to fulfill sophisticated biophysical, cell signalling, and endocrine functions in animal systems. At the cellular level, cholesterol is found in membranes where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signalling functions. At the organismal level, cholesterol is the precursor of all steroid hormones, including gluco- and mineralo-corticoids, sex hormones, and vitamin D, which regulate carbohydrate, sodium, reproductive, and bone homeostasis, respectively. This sterol is also the immediate precursor of bile acids, which are important for intestinal absorption of dietary lipids as well as energy homeostasis and glucose regulation. Complex mechanisms maintain cholesterol within physiological ranges and the dysregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these conditions has been demonstrated by genetic and pharmacological manipulations in animal models of human disease that are discussed herein. Importantly, the understanding of basic aspects of cholesterol biology has led to the development of high-impact pharmaceutical therapies during the past century. The continuing effort to offer successful treatments for prevalent cholesterol-related diseases, such as atherosclerosis and neurodegenerative disorders, warrants further interdisciplinary research in the coming decades. PMID:23445165

  4. 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....

  5. Effect of doxazosin on cholesterol synthesis in cell culture

    Energy Technology Data Exchange (ETDEWEB)

    D' Eletto, R.D.; Javitt, N.B.

    1989-01-01

    The effect of doxazosin on cholesterol synthesis was determined by measuring the content of deuterium-enriched cholesterol in rabbit fibroblasts with and without receptors for low-density lipoproteins (LDL) and in hepatoma (Hep G2 cells). Doxazosin, at concentrations of 5-20 mumol/L, increased LDL binding to hepatic cells in a dose-related manner. Also, in these hepatic cells, doxazosin produced dose-related decreases in both newly synthesized cholesterol and cholesterol ester. In rabbit fibroblasts that were LDL receptor negative, de novo cholesterol synthesis was markedly reduced by increasing concentrations of doxazosin. Taken together, these results suggest that doxazosin may have a direct inhibitory effect on cholesterol synthesis independent of the LDL receptor. The inhibition of cholesterol synthesis by doxazosin may cause cells to compensate by upregulating the LDL receptor, thereby increasing the importation of lipoprotein cholesterol and reducing LDL cholesterol in the medium. This hypothesis supports findings in the clinical setting whereby doxazosin has a beneficial effect on the lipid profile, and suggests a useful additional property for this antihypertensive agent.

  6. Application of backtracking algorithm to depletion calculations

    International Nuclear Information System (INIS)

    Based on the theory of linear chain method for analytical depletion calculations, the burn-up matrix is decoupled by the divide and conquer strategy and the linear chain with Markov characteristic is formed. The density, activity and decay heat of every nuclide in the chain can be calculated by analytical solutions. Every possible reaction path of the nuclide must be considered during the linear chain establishment process. To confirm the calculation precision and efficiency, the algorithm which can cover all the reaction paths of the nuclide and search the paths automatically according to to problem description and precision restrictions should be sought. Through analysis and comparison of several kinds of searching algorithms, the backtracking algorithm was selected to search and calculate the linear chains using Depth First Search (DFS) method. The depletion program can solve the depletion problem adaptively and with high fidelity. The solution space and time complexity of the program were analyzed. The new developed depletion program was coupled with Monte Carlo program MCMG-II to calculate the benchmark burn-up problem of the first core of China Experimental Fast Reactor (CEFR). The initial verification and validation of the program was performed by the calculation. (author)

  7. Global Warming: Lessons from Ozone Depletion

    Science.gov (United States)

    Hobson, Art

    2010-01-01

    My teaching and textbook have always covered many physics-related social issues, including stratospheric ozone depletion and global warming. The ozone saga is an inspiring good-news story that's instructive for solving the similar but bigger problem of global warming. Thus, as soon as students in my physics literacy course at the University of…

  8. Apoprotein E phenotype determines serum cholesterol in infants during both high-cholesterol breast feeding and low-cholesterol formula feeding.

    Science.gov (United States)

    Kallio, M J; Salmenperä, L; Siimes, M A; Perheentupa, J; Gylling, H; Miettinen, T A

    1997-04-01

    Our objective was to establish the role of the apoprotein (apo) E phenotype in determining serum cholesterol levels in infants fed exclusively on high-fat, high-cholesterol human milk and in those fed a low-cholesterol, high-unsaturated fat formula. The total and lipoprotein cholesterol, apoB, and triglyceride concentrations in serum were quantified and related to the apoE phenotype in 151 infants at birth and at 2, 6, 9, and 12 months of age. Forty-four had the E3/4 or 4/4 phenotype (E4 group), 94 had the E3/3 phenotype (E3 group), and 13 had the E2/3 or 2/4 phenotype (E2 group). In cord blood, cholesterol concentrations tended to be higher in the E4 than in the E2 group. With exclusive breast-feeding, the concentrations rose significantly faster and higher in the E4 group than in the E3 group or, especially, the E2 group. The values (mmol/L, mean +/- SEM) were 1.6 +/- 0.15, 1.5 +/- 0.05, 1.4 +/- 0.1 (P = n.s.) at birth; 4.2 +/- 0.1, 3.8 +/- 0.08, 3.4 +/- 0.2 (P HDL, HDL2, and HDL3 cholesterol concentrations did not depend on the apoE phenotype. Among infants fed high-fat, high-cholesterol human milk, the total and LDL-cholesterol concentrations and the LDL apoB concentration of those with the apoE phenotype 4/4 or 3/4 rose faster and to higher levels than in other infants. Among formula-fed infants, receiving a low-cholesterol, high-unsaturated fat diet, the differences between the apoE groups were smaller.

  9. Saturated fatty acid (SFA) status and SFA intake exhibit different relations with serum total cholesterol and lipoprotein cholesterol : a mechanistic explanation centered around lifestyle-induced low-grade inflammation

    NARCIS (Netherlands)

    Ruiz Nunez, Begona; Kuipers, Remko S.; Luxwolda, Martine F.; De Graaf, Deti J.; Breeuwsma, Benjamin B.; Dijck-Brouwer, Janneke; Muskiet, Frits A. J.

    2014-01-01

    We investigated the relations between fatty acid status and serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol and total cholesterol/HDL cholesterol ratio in five Tanzanian ethnic groups and one Dutch group. Total cholesterol/HDL cholesterol rati

  10. 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

  11. 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

  12. How Depleted is the MORB mantle?

    Science.gov (United States)

    Hofmann, A. W.; Hart, S. R.

    2015-12-01

    Knowledge of the degree of mantle depletion of highly incompatible elements is critically important for assessing Earth's internal heat production and Urey number. Current views of the degree of MORB source depletion are dominated by Salters and Stracke (2004), and Workman and Hart (2005). The first is based on an assessment of average MORB compositions, whereas the second considers trace element data of oceanic peridotites. Both require an independent determination of one absolute concentration, Lu (Salters & Stracke), or Nd (Workman & Hart). Both use parent-daughter ratios Lu/Hf, Sm/Nd, and Rb/Sr calculated from MORB isotopes combined with continental-crust extraction models, as well as "canonical" trace element ratios, to boot-strap the full range of trace element abundances. We show that the single most important factor in determining the ultimate degree of incompatible element depletion in the MORB source lies in the assumptions about the timing of continent extraction, exemplified by continuous extraction versus simple two-stage models. Continued crust extraction generates additional, recent mantle depletion, without affecting the isotopic composition of the residual mantle significantly. Previous emphasis on chemical compositions of MORB and/or peridotites has tended to obscure this. We will explore the effect of different continent extraction models on the degree of U, Th, and K depletion in the MORB source. Given the uncertainties of the two most popular models, the uncertainties of U and Th in DMM are at least ±50%, and this impacts the constraints on the terrestrial Urey ratio. Salters, F.J.M. and Stracke, A., 2004, Geochem. Geophys. Geosyst. 5, Q05004. Workman, R.K. and Hart, S.R., 2005, EPSL 231, 53-72.

  13. The Role of Oxidized Cholesterol in Diabetes-Induced Lysosomal Dysfunction in the Brain.

    Science.gov (United States)

    Sims-Robinson, Catrina; Bakeman, Anna; Rosko, Andrew; Glasser, Rebecca; Feldman, Eva L

    2016-05-01

    Abnormalities in lysosomal function have been reported in diabetes, aging, and age-related degenerative diseases. These lysosomal abnormalities are an early manifestation of neurodegenerative diseases and often precede the onset of clinical symptoms such as learning and memory deficits; however, the mechanism underlying lysosomal dysfunction is not known. In the current study, we investigated the mechanism underlying lysosomal dysfunction in the cortex and hippocampi, key structures involved in learning and memory, of a type 2 diabetes (T2D) mouse model, the leptin receptor deficient db/db mouse. We demonstrate for the first time that diabetes leads to destabilization of lysosomes as well as alterations in the protein expression, activity, and/or trafficking of two lysosomal enzymes, hexosaminidase A and cathepsin D, in the hippocampus of db/db mice. Pioglitazone, a thiazolidinedione (TZD) commonly used in the treatment of diabetes due to its ability to improve insulin sensitivity and reverse hyperglycemia, was ineffective in reversing the diabetes-induced changes on lysosomal enzymes. Our previous work revealed that pioglitazone does not reverse hypercholesterolemia; thus, we investigated whether cholesterol plays a role in diabetes-induced lysosomal changes. In vitro, cholesterol promoted the destabilization of lysosomes, suggesting that lysosomal-related changes associated with diabetes are due to elevated levels of cholesterol. Since lysosome dysfunction precedes neurodegeneration, cognitive deficits, and Alzheimer's disease neuropathology, our results may provide a potential mechanism that links diabetes with complications of the central nervous system. PMID:25976368

  14. Redistribution of Cholesterol in Model Lipid Membranes in Response to the Membrane-Active Peptide Alamethicin

    Science.gov (United States)

    Heller, William; Qian, Shuo

    2013-03-01

    The cellular membrane is a heterogeneous, dynamic mixture of molecules and macromolecules that self-assemble into a tightly-regulated functional unit that provides a semipermeable barrier between the cell and its environment. Among the many compositional differences between mammalian and bacterial cell membranes that impact its physical properties, one key difference is cholesterol content, which is more prevalent in mammals. Cholesterol is an amphiphile that associates with membranes and serves to maintain its fluidity and permeability. Membrane-active peptides, such as the alpha-helical peptide alamethicin, interact with membranes in a concentration- and composition-dependent manner to form transmembrane pores that are responsible for the lytic action of the peptide. Through the use of small-angle neutron scattering and deuterium labeling, it was possible to observe a redistribution of the lipid and cholesterol in unilamellar vesicles in response to the presence of alamethicin at a peptide-to-lipid ratio of 1/200. The results demonstrate that the membrane remodeling powers of alamethicin reach beyond the membrane thinning effect to altering the localization of specific components in the bilayer, complementing the accepted two-state mechanism of pore formation. Research was supported by U. S. DOE-OBER (CSMB; FWP ERKP291) and the U. S. DOE-BES Scientific User Facilities Division (ORNL's SNS and HFIR).

  15. Overexpression of the cholesterol-binding protein MLN64 induces liver damage in the mouse

    Institute of Scientific and Technical Information of China (English)

    Juan Enrique Tichauer; Juan Francisco Miquel; Attilio Rigotti; Silvana Zanlungo; Mar(i)a Gabriela Morales; Ludwig Amigo; Leopoldo Galdames; Andrés Kléin; Verónica Quifio(n)es; Carla Ferrada; Alejandra Alvarez R; Marie-Christine Rio

    2007-01-01

    AIM: To examine the in vivo phenotype associated with hepatic metastatic lymph node 64 (MLN64) over-expression.METHODS: Recombinant-adenovirus-mediated MLN64 gene transfer was used to overexpress MLN64 in the livers of C57BL/6 mice. We measured the effects of MLN64 overexpression on hepatic cholesterol content, bile flow, biliary lipid secretion and apoptosis markers. For in vitro studies cultured CHO cells with transient MLN64 overexpression were utilized and apoptosis by TUNEL assay was measured.RESULTS: Livers from Ad.MLN64-infected mice exhibited early onset of liver damage and apoptosis. This response correlated with increases in liver cholesterol content and biliary bile acid concentration, and impaired bile flow. We investigated whether liver MLN64 expression could be modulated in a murine model of hepatic injury. We found increased hepatic MLN64 mRNA and protein levels in mice with chenodeoxycholic acid-induced liver damage. In addition, cultured CHO cells with transient MLN64 overexpression showed increased apoptosis.CONCLUSION: In summary, hepatic MLN64 over-expression induced damage and apoptosis in murine livers and altered cholesterol metabolism. Further studies are required to elucidate the relevance of these findings under physiologic and disease conditions.

  16. Haptoglobin increases with age in rat hippocampus and modulates Apolipoprotein E mediated cholesterol trafficking in neuroblastoma cell lines

    Directory of Open Access Journals (Sweden)

    Maria Stefania eSpagnuolo

    2014-08-01

    Full Text Available Alteration in cholesterol metabolism has been implicated in the pathogenesis of several neurodegenerative disorders. Apolipoprotein E (ApoE is the major component of brain lipoproteins supporting cholesterol transport. We previously reported that the acute-phase protein Haptoglobin (Hpt binds ApoE, and influences its function in blood cholesterol homeostasis. Major aim of this study was to investigate whether Hpt influences the mechanisms by which cholesterol is shuttled from astrocytes to neurons. In detail it was studied Hpt effect on ApoE-dependent cholesterol efflux from astrocytes and ApoE-mediated cholesterol incorporation in neurons. We report here that Hpt impairs ApoE-mediated cholesterol uptake in human neuroblastoma cell line SH-SY5Y, and limits the toxicity of a massive concentration of cholesterol for these cells, while it does not affect cholesterol efflux from the human glioblastoma-astrocytoma cell line U-87 MG. As aging is the most important nongenetic risk factor for various neurodegenerative disorders, and our results suggest that Hpt modulates ApoE functions, we evaluated the Hpt and ApoE expression profiles in cerebral cortex and hippocampus of adolescent (2 months, adult (5 and 8 months, and middle-aged (16 months rats. Hpt mRNA level was higher in hippocampus of 8 and 16 month-old than in 2-month old rats (p<0.05, and Hpt concentration increased with the age from adolescence to middle-age (p<0.001. ApoE concentration, in hippocampus, was higher (p<0.001 in 5 month-old rats compared to 2 month but did not further change with aging. No age-related changes of Hpt (protein and mRNA were found in the cortex. Our results suggest that aging is associated with changes, particularly in the hippocampus, in the Hpt/ApoE ratio. Age-related changes in the concentration of Hpt were also found in human cerebrospinal fluids.The age-related changes might affect neuronal function and survival in brain, and have important implications in

  17. LDL Cholesterol, Statins And PCSK 9 Inhibitors

    Science.gov (United States)

    Gupta, Sanjiv

    2015-01-01

    Reduction of low density lipoprotein cholesterol (LDLc) is of vital importance for the prevention of atherosclerotic cardiovascular disease (ASCVD). Statin is the most effective therapy today to lower LDLc by inhibiting HMG-CoA-reductase. However despite intensive statin therapy, there remains a residual risk of recurrent myocardial infarction in about 20–30% cases. Moreover a few patients develop statin intolerance. For severe hypercholesterolemia, statins alone or in combination of ezetimibe, niacin and fenofibrate have been advocated. For homozygous familial hypercholesterolemia (HOFH), a microsomal triglyceride transfer protein MTP inhibitor (Lopitamide) and antisense oligonucleotide (ASO) (Mipomersen) have recently been approved by FDA, USA through ‘Risk evaluation and Mitigation Strategy (REMS)’. Possible future therapies include PCSK-9 inhibitors which have excellent lipid lowering properties. Three monoclonal antibodies (PCSK 9 Inhibitors) alirocumab, evolocumab and Bococizumab are under advanced clinical stage IV trials and awaiting approval by FDA and European Medicines Agency. PMID:26432726

  18. 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

  19. Glucosylated cholesterol in mammalian cells and tissues: formation and degradation by multiple cellular β-glucosidases.

    Science.gov (United States)

    Marques, André R A; Mirzaian, Mina; Akiyama, Hisako; Wisse, Patrick; Ferraz, Maria J; Gaspar, Paulo; Ghauharali-van der Vlugt, Karen; Meijer, Rianne; Giraldo, Pilar; Alfonso, Pilar; Irún, Pilar; Dahl, Maria; Karlsson, Stefan; Pavlova, Elena V; Cox, Timothy M; Scheij, Saskia; Verhoek, Marri; Ottenhoff, Roelof; van Roomen, Cindy P A A; Pannu, Navraj S; van Eijk, Marco; Dekker, Nick; Boot, Rolf G; Overkleeft, Herman S; Blommaart, Edward; Hirabayashi, Yoshio; Aerts, Johannes M

    2016-03-01

    The membrane lipid glucosylceramide (GlcCer) is continuously formed and degraded. Cells express two GlcCer-degrading β-glucosidases, glucocerebrosidase (GBA) and GBA2, located in and outside the lysosome, respectively. Here we demonstrate that through transglucosylation both GBA and GBA2 are able to catalyze in vitro the transfer of glucosyl-moieties from GlcCer to cholesterol, and vice versa. Furthermore, the natural occurrence of 1-O-cholesteryl-β-D-glucopyranoside (GlcChol) in mouse tissues and human plasma is demonstrated using LC-MS/MS and (13)C6-labeled GlcChol as internal standard. In cells, the inhibition of GBA increases GlcChol, whereas inhibition of GBA2 decreases glucosylated sterol. Similarly, in GBA2-deficient mice, GlcChol is reduced. Depletion of GlcCer by inhibition of GlcCer synthase decreases GlcChol in cells and likewise in plasma of inhibitor-treated Gaucher disease patients. In tissues of mice with Niemann-Pick type C disease, a condition characterized by intralysosomal accumulation of cholesterol, marked elevations in GlcChol occur as well. When lysosomal accumulation of cholesterol is induced in cultured cells, GlcChol is formed via lysosomal GBA. This illustrates that reversible transglucosylation reactions are highly dependent on local availability of suitable acceptors. In conclusion, mammalian tissues contain GlcChol formed by transglucosylation through β-glucosidases using GlcCer as donor. Our findings reveal a novel metabolic function for GlcCer. PMID:26724485

  20. A worldwide view of groundwater depletion

    Science.gov (United States)

    van Beek, L. P.; Wada, Y.; van Kempen, C.; Reckman, J. W.; Vasak, S.; Bierkens, M. F.

    2010-12-01

    During the last decades, global water demand has increased two-fold due to increasing population, expanding irrigated area and economic development. Globally such demand can be met by surface water availability (i.e., water in rivers, lakes and reservoirs) but regional variations are large and the absence of sufficient rainfall and run-off increasingly encourages the use of groundwater resources, particularly in the (semi-)arid regions of the world. Excessive abstraction for irrigation frequently leads to overexploitation, i.e. if groundwater abstraction exceeds the natural groundwater recharge over extensive areas and prolonged times, persistent groundwater depletion may occur. Observations and various regional studies have revealed that groundwater depletion is a substantial issue in regions such as Northwest India, Northeast Pakistan, Central USA, Northeast China and Iran. Here we provide a global overview of groundwater depletion from the year 1960 to 2000 at a spatial resolution of 0.5 degree by assessing groundwater recharge with the global hydrological model PCR-GLOBWB and subtracting estimates of groundwater abstraction obtained from IGRAC-GGIS database. PCR-GLOBWB was forced by the CRU climate dataset downscaled to daily time steps using ERA40 re-analysis data. PCR-GLOBWB simulates daily global groundwater recharge (0.5 degree) while considering sub-grid variability of each grid cell (e.g., short and tall vegetation, different soil types, fraction of saturated soil). Country statistics of groundwater abstraction were downscaled to 0.5 degree by using water demand (i.e., agriculture, industry and domestic) as a proxy. To limit problems related to increased capture of discharge and increased recharge due to groundwater pumping, we restricted our analysis to sub-humid to arid areas. The uncertainty in the resulting estimates was assessed by a Monte Carlo analysis of 100 realizations of groundwater recharge and 100 realizations of groundwater abstraction