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https://www.readbyqxmd.com/read/29675736/decreased-content-rate-of-synthesis-and-export-of-cholesterol-in-the-brain-of-apoe-knockout-mice
#1
Valéria Sutti Nunes, Patrícia Miralda Cazita, Sérgio Catanozi, Edna Regina Nakandakare, Eder Carlos Rocha Quintão
Apolipoprotein E knockout (apoE-KO) mice present synaptic loss, cognitive dysfunction, and high plasma lipid levels that may affect brain function simulating Alzheimer disease. Plasma and brain sterols were measured in apoE-KO and in wild type control mice on a cholesterol-free, phytosterol-containing diet by gas chromatography coupled to a mass spectrometer. Plasma cholesterol and phytosterols (campesterol and sitosterol) were higher in apoE-KO compared to control mice. Cholesterol precursors (desmosterol and lathosterol) were not detected in plasma of control mice but were present in apoE-KO mice...
April 20, 2018: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29663389/noncholesterol-sterols-as-surrogate-markers-in-patients-with-severe-alcoholic-hepatitis
#2
Perttu Sahlman, Markku Nissinen, Piia Simonen, Martti Färkkilä
Severe alcoholic hepatitis (AH) is a life-threatening condition lacking good serologic markers to tailor treatment and predict recovery. We examined the cholesterol metabolism in severe AH to explore prognostic markers and evaluate the profile of cholesterol precursors, cholestanol and phytosterols, in this context. We assessed serum cholesterol, cholesterol precursors, cholestanol, phytosterols, and biochemical markers in 24 patients with severe AH treated with prednisolone and randomized to ciprofloxacin in the ratio 1:1...
April 16, 2018: Lipids
https://www.readbyqxmd.com/read/29535640/identification-of-discriminating-metabolic-pathways-and-metabolites-in-human-pbmcs-stimulated-by-various-pathogenic-agents
#3
Xiang Zhang, Adil Mardinoglu, Leo A B Joosten, Jan A Kuivenhoven, Yang Li, Mihai G Netea, Albert K Groen
Immunity and cellular metabolism are tightly interconnected but it is not clear whether different pathogens elicit specific metabolic responses. To address this issue, we studied differential metabolic regulation in peripheral blood mononuclear cells (PBMCs) of healthy volunteers challenged by Candida albicans, Borrelia burgdorferi , lipopolysaccharide, and Mycobacterium tuberculosis in vitro . By integrating gene expression data of stimulated PBMCs of healthy individuals with the KEGG pathways, we identified both common and pathogen-specific regulated pathways depending on the time of incubation...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29407218/membrane-cholesterol-removal-and-replenishment-affect-rat-and-monkey-brain-monoamine-transporters
#4
Marc Morissette, Nicolas Morin, Claude Rouillard, Thérèse Di Paolo
The dopamine transporter (DAT) is abundantly expressed in the striatum where it removes extracellular dopamine into the cytosol of presynaptic nerve terminals. It is the target of drugs of abuse and antidepressants. There is a loss of the DAT in Parkinson's disease affecting release of levodopa implicated in levodopa-induced dyskinesias. This study investigated the effect of cholesterol on DAT, serotonin transporter (SERT) and vesicular monoamine transporter 2 (VMAT2) in monkey and rat brains in vitro. DAT protein levels measured by Western blot remained unchanged with in vitro methyl-β-cyclodextrin (MCD) incubations to remove membrane cholesterol or with incubations to increase membrane cholesterol content...
January 30, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29369630/sterols-in-infant-formulas-a-bioaccessibility-study
#5
Islam J A Hamdan, Luis Manuel Sanchez-Siles, Guadalupe Garcia-Llatas, María Jesús Lagarda
The design of infant formulas (IFs) seeks to resemble human milk (HM) composition and functionality. The fat sources used usually comprise vegetable oil blends to mimic the fatty acid composition of HM and introduce changes in the animal/plant sterol ratio. In contrast, the use of milk fat globule membrane (MFGM)-rich ingredients could improve this aspect by increasing the ratio. The present study evaluates the bioaccessibility (BA) of sterols (cholesterol, desmosterol, brassicasterol, campesterol, stigmasterol, and β-sitosterol) in three IFs (with or without MFGM) using an in vitro digestion method simulating infant conditions...
February 14, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29334954/association-between-non-cholesterol-sterol-concentrations-and-achilles-tendon-thickness-in-patients-with-genetic-familial-hypercholesterolemia
#6
Lucía Baila-Rueda, Itziar Lamiquiz-Moneo, Estíbaliz Jarauta, Rocío Mateo-Gallego, Sofía Perez-Calahorra, Victoria Marco-Benedí, Ana M Bea, Ana Cenarro, Fernando Civeira
BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder that result in abnormally high low-density lipoprotein cholesterol levels, markedly increased risk of coronary heart disease (CHD) and tendon xanthomas (TX). However, the clinical expression is highly variable. TX are present in other metabolic diseases that associate increased sterol concentration. If non-cholesterol sterols are involved in the development of TX in FH has not been analyzed. METHODS: Clinical and biochemical characteristics, non-cholesterol sterols concentrations and Aquilles tendon thickness were determined in subjects with genetic FH with (n = 63) and without (n = 40) TX...
January 15, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29327426/quantification-of-total-cholesterol-in-human-milk-by-gas-chromatography
#7
Maurizio Beggio, Cristina Cruz-Hernandez, Pierre-Alain Golay, Le Ye Lee, Francesca Giuffrida
Human milk provides the key nutrients necessary for infant growth and development. The objective of this study was to develop and validate a method to analyze the cholesterol content in liquid human milk samples along lactation. Direct saponification of the sample using ethanolic potassium hydroxide solution under cold conditions was applied and unsaponifiable matter was separated by centrifugation. Cholesterol was converted into its trimethylsilyl ether and the derivative analyzed by gas chromatography coupled with a flame ionization detector...
January 12, 2018: Journal of Separation Science
https://www.readbyqxmd.com/read/29324705/influence-of-chitosan-treatment-on-surrogate-serum-markers-of-cholesterol-metabolism-in-obese-subjects
#8
Dieter Lütjohann, Milka Marinova, Karsten Wolter, Winfried Willinek, Norman Bitterlich, Martin Coenen, Christoph Coch, Frans Stellaard
Chitosan treatment results in significantly lower serum low density lipoprotein (LDL) cholesterol concentrations. To assess the working mechanisms of chitosan, we measured serum surrogate markers of cholesterol absorption (campesterol, sitosterol, cholestanol), synthesis (lathosterol, lanosterol, desmosterol), and degradation to bile acids (7α-hydroxy-cholesterol, 27-hydroxy-cholesterol), corrected for cholesterol concentration (R_sterols). Over 12 weeks, 116 obese subjects (Body Mass Index, BMI 31.7, range 28...
January 11, 2018: Nutrients
https://www.readbyqxmd.com/read/29274328/preanalytical-and-analytical-challenges-in-gas-chromatographic-determination-of-cholesterol-synthesis-and-absorption-markers
#9
Tamara Gojkovic, Sandra Vladimirov, Vesna Spasojevic-Kalimanovska, Aleksandra Zeljkovic, Jelena Vekic, Jelena Arsenijevic, Ivana Djuricic, Sladjana Sobajic, Zorana Jelic-Ivanovic
INTRODUCTION: Cholesterol homeostasis disruption contributes to the development of different pathologies. Non-cholesterol sterols (NCSs) serve as cholesterol synthesis markers (desmosterol and lathosterol), and cholesterol absorption surrogate markers (campesterol, stigmasterol and β-sitosterol). The study aimed to resolve certain new pre-analytical and analytical problems and ensure a reliable and validated method. MATERIALS AND METHODS: Method optimization, validation and stability studies were executed in human serum and plasma...
March 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29197826/effects-of-host-cell-sterol-composition-upon-internalization-of-yersinia-pseudotuberculosis-and-clustered-%C3%AE-1-integrin
#10
JiHyun Kim, Hana S Fukuto, Deborah A Brown, James B Bliska, Erwin London
Yersinia pseudotuberculosis is a foodborne pathogenic bacterium that causes acute gastrointestinal illness, but its mechanisms of infection are incompletely described. We examined how host cell sterol composition affected Y. pseudotuberculosis uptake. To do this, we depleted or substituted cholesterol in human MDA-MB-231 epithelial cells with various alternative sterols. Decreasing host cell cholesterol significantly reduced pathogen internalization. When host cell cholesterol was substituted with various sterols, only desmosterol and 7-dehydrocholesterol supported internalization...
January 26, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29190549/cholesterol-oversynthesis-markers-define-familial-combined-hyperlipidemia-versus-other-genetic-hypercholesterolemias-independently-of-body-weight
#11
Lucía Baila-Rueda, Ana Cenarro, Itziar Lamiquiz-Moneo, Sofía Perez-Calahorra, Ana M Bea, Victoria Marco-Benedí, Estíbaliz Jarauta, Rocío Mateo-Gallego, Fernando Civeira
Primary hypercholesterolemia of genetic origin, negative for mutations in LDLR, APOB, PCSK9 and APOE genes (non-FH GH), and familial combined hyperlipidemia (FCHL) are polygenic genetic diseases that occur with hypercholesterolemia, and both share a very high cardiovascular risk. In order to better characterize the metabolic abnormalities associated with these primary hypercholesterolemias, we used noncholesterol sterols, as markers of cholesterol metabolism, to determine their potential differences. Hepatic cholesterol synthesis markers (desmosterol and lanosterol) and intestinal cholesterol absorption markers (sitosterol and campesterol) were determined in non-FH GH (n=200), FCHL (n=100) and genetically defined heterozygous familial hypercholesterolemia subjects (FH) (n=100) and in normolipidemic controls (n=100)...
March 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29178237/cholesterol-and-desmosterol-dancing-to-the-beat-of-a-different-drug
#12
A J Brown, I C Gelissen
No abstract text is available yet for this article.
January 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29175559/desmosterolosis-presenting-with-multiple-congenital-anomalies
#13
Mersedeh Rohanizadegan, Stephanie Sacharow
Desmosterolosis is a rare multiple congenital anomaly syndrome caused by a defect in the enzyme 3-beta-hydroxysterol delta-24-reductase (DHCR24) in the cholesterol biosynthesis pathway. Defects in this enzyme cause increased level of the cholesterol precursor desmosterol while disrupting development of cholesterol, impacting embryogenesis. A total of 9 cases of desmosterolosis have been reported to date. We report a 20-month-old male from consanguineous parents with multiple congenital anomalies including corpus callosum hypoplasia, facial dysmorphism, cleft palate, pectus deformity, short and wide neck and distal contractures...
March 2018: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29115523/characterization-of-cholesterol-metabolism-in-sertoli-cells-and-spermatogenesis-review
#14
Jin-Feng Shi, Yu-Kun Li, Kun Ren, Yuan-Jie Xie, Wei-Dong Yin, Zhong-Cheng Mo
The Sertoli cell, which is the supporting cell of spermatogenesis, has an important role in the endocrine and paracrine control of spermatogenesis. Functionally, it provides the cells of the seminiferous epithelium with nutrition, conveys mature spermatids to the lumen of seminiferous tubules, secretes androgen‑binding protein and interacts with endocrine Leydig cells. In addition, the levels of cholesterol, as well as its intermediates, vary greatly between nongonadal tissues and the male reproductive system...
January 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29042617/expression-and-function-of-abcg4-in-the-mouse-blood-brain-barrier-role-in-restricting-the-brain-entry-of-amyloid-%C3%AE-peptide
#15
Agnès Dodacki, Matthew Wortman, Bruno Saubaméa, Stéphanie Chasseigneaux, Sophie Nicolic, Nathalie Prince, Murielle Lochus, Anne-Laure Raveu, Xavier Declèves, Jean-Michel Scherrmann, Shailendra B Patel, Fanchon Bourasset
ABCG4 is an ATP-binding cassette transmembrane protein which has been shown, in vitro, to participate in the cellular efflux of desmosterol and amyloid-β peptide (Aβ). ABCG4 is highly expressed in the brain, but its localization and function at the blood-brain barrier (BBB) level remain unknown. We demonstrate by qRT-PCR and confocal imaging that mouse Abcg4 is expressed in the brain capillary endothelial cells. Modelling studies of the Abcg4 dimer suggested that desmosterol showed thermodynamically favorable binding at the putative sterol-binding site, and this was greater than for cholesterol...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28964935/new-chemotype-of-selective-and-potent-inhibitors-of-human-delta-24-dehydrocholesterol-reductase
#16
Christoph Müller, Sandra Hemmers, Nicholas Bartl, Alois Plodek, Andreas Körner, Valbona Mirakaj, Martin Giera, Franz Bracher
The enzyme Δ24 -dehydrocholesterol reductase (DHCR24) catalyzes the reduction of the Δ24 -double bond in the side chain of cholesterol precursors. Recent biochemical investigations fuel the hope that inhibition of DHCR24, resulting in an accumulation of desmosterol, can open new therapeutic options for treating hepatitis C virus infections, certain forms of cancer and atherosclerosis. In turn, there is a high need for selective, potent and non-toxic inhibitors of DHCR24. Previous reports as well as our re-evaluation showed that established DHCR24 inhibitors are not suitable for this purpose...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28945984/modification-of-membrane-cholesterol-and-desmosterol-in-chicken-spermatozoa-improves-post-thaw-survival-and-prevents-impairment-of-sperm-function-after-cryopreservation
#17
Ai Ushiyama, Atsushi Tajima, Naoto Ishikawa, Atsushi Asano
During cryopreservation, spermatozoa are subjected to cryodamage that leads to a decline in fertilisation ability. Due to the complex nature of this process, the initial trigger for cryodamage remains unknown. Recently, we demonstrated that cryopreservation induces early apoptotic changes characterised by phosphatidylserine (PS) translocation via sterol loss from the plasma membrane of chicken spermatozoa. This led us to hypothesise that sterol incorporation into membranes minimises cryodamage, thereby improving the quality of cryopreserved chicken spermatozoa...
September 26, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28886149/plasma-sterols-and-depressive-symptom-severity-in-a-population-based-cohort
#18
Basar Cenik, Can Cenik, Michael P Snyder, E Sherwood Brown
Convergent evidence strongly suggests major depressive disorder is heterogeneous in its etiology and clinical characteristics. Depression biomarkers hold potential for identifying etiological subtypes, improving diagnostic accuracy, predicting treatment response, and personalization of treatment. Human plasma contains numerous sterols that have not been systematically studied. Changes in cholesterol concentrations have been implicated in suicide and depression, suggesting plasma sterols may be depression biomarkers...
2017: PloS One
https://www.readbyqxmd.com/read/28861933/desmosterol-accumulation-in-users-of-amiodarone
#19
P Simonen, J Lehtonen, A-M Lampi, V Piironen, U-H Stenman, M Kupari, H Gylling
BACKGROUND: Amiodarone is an effective and widely used antiarrhythmic drug with many possible adverse effects including hypercholesterolaemia and hepatotoxicity. OBJECTIVE: Our aim was to evaluate how long-term amiodarone treatment affects cholesterol metabolism. METHODS: The study population consisted of 56 cardiac patients, of whom 20 were on amiodarone (amiodarone + group) and 36 did not use the drug (amiodarone - group). We also studied a control group of 124 individuals selected randomly from the population...
January 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28807695/doxorubicin-enhances-oxysterol-levels-resulting-in-a-lxr-mediated-upregulation-of-cardiac-cholesterol-transporters
#20
Judith V Monzel, Thomas Budde, Henriette E Meyer Zu Schwabedissen, Matthias Schwebe, Sandra Bien-Möller, Dieter Lütjohann, Heyo K Kroemer, Gabriele Jedlitschky, Markus Grube
The anthracycline-mediated cardiotoxicity is still not completely understood. To examine the impact of cholesterol metabolism and transport in this context, cholesterol and oxysterol levels as well as the expression of the cholesterol transporters ABCA1 and ABCG1 were analyzed in doxorubicin-treated HL-1 murine cardiomyocytes as well as in mouse model for acute doxorubicin-induced cardiotoxicity. Doxorubicin-treated HL-1 cells exhibited enhanced cholesterol (153±20% of control), oxysterol (24S-hydroxycholesterol: 206±29% of control) and cholesterol precursor levels (lathosterol: 122±12% of control; desmosterol: 188±10% of control) indicating enhanced cholesterol synthesis...
November 15, 2017: Biochemical Pharmacology
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