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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...
August 11, 2017: Biochemical Pharmacology
Kinga Stuper-Szablewska, Tomasz Rogoziński, Juliusz Perkowski
Wood compounds, especially sterols, are connected with the level of contamination with microscopic fungi. Within this study, tests were conducted on wood dust samples collected at various work stations in a pine and birch timber conversion plant. Their contamination with mycobiota was measured as the concentration of ergosterol (ERG) by ultra performance liquid chromatography (UPLC). Another aim of this study was to assess the effect of contamination with microscopic fungi on the sterol contents in wood dusts...
June 27, 2017: Arhiv za Higijenu Rada i Toksikologiju
Ho Viet Duc, Hoang Thi Nhu Hang, Vo Quoc Hung, Nguyen Minh Hien, Ain Raal, Nguyen Thi Hoai
The aim of the research was to study the active constituents of Anodendron paniculatum Roxb. (Apocynaceae). A new triterpene ester, named anopaniester (1), and cycloartenol (2), ursolic acid (3), esculenic acid (4), bis-(2-ethylhexyl) phthalate (5), desmosterol (6), stigmasterol (7), vaniline (8), and (E)-phytol (9), were isolated from the aerial parts of A. paniculatum. Compounds 3 and 6 showed the significant inhibitory effect (IC50 values ranging from 30.89 ± 3.60 to 44.37 ± 5.40 μg/ml) against tested human cancer cell lines LU-1 and MKN-7...
June 28, 2017: Journal of Asian Natural Products Research
George A Wudiri, Anthony V Nicola
Cholesterol is an essential component of cell membranes and is required for herpes simplex virus 1 (HSV-1) entry (1-3). Treatment of HSV-1-infected Vero cells with methyl beta-cyclodextrin from 2 to 9 h postentry reduced plaque numbers. Transport of incoming viral capsids to the nuclear periphery was unaffected by the cholesterol reduction, suggesting that cell cholesterol is important for the HSV-1 replicative cycle at a stage(s) beyond entry, after the arrival of capsids at the nucleus. The synthesis and release of infectious HSV-1 and cell-to-cell spread of infection were all impaired in cholesterol-reduced cells...
July 15, 2017: Journal of Virology
Ole G Mouritsen, Luis A Bagatolli, Lars Duelund, Olav Garvik, John H Ipsen, Adam Cohen Simonsen
Higher sterols are universally present in large amounts (20-30%) in the plasma membranes of all eukaryotes whereas they are universally absent in prokaryotes. It is remarkable that each kingdom of the eukaryotes has chosen, during the course of evolution, its preferred sterol: cholesterol in animals, ergosterol in fungi and yeast, phytosterols in higher plants, and e.g., fucosterol and desmosterol in algae. The question arises as to which specific properties do sterols impart to membranes and to which extent do these properties differ among the different sterols...
June 2017: Chemistry and Physics of Lipids
Islam J A Hamdan, Lorena Claumarchirant, Guadalupe Garcia-Llatas, Amparo Alegría, María Jesús Lagarda
Sterols are components present in the fat fraction of infant formulas (IFs). Their characterization is therefore of interest, though there are no official reference methods for their analysis in these matrices. AIM: To validate a gas chromatographic method with flame ionization detection for the determination of animal (cholesterol and desmosterol) and plant sterols (brassicasterol, campesterol, stigmasterol, β-sitosterol and sitostanol) found in IFs. All correlation coefficients obtained for the calibration curves of sterols studied were >0...
February 16, 2017: International Journal of Food Sciences and Nutrition
Željka Korade, Wei Liu, Emily B Warren, Kristan Armstrong, Ned A Porter, Christine Konradi
Cholesterol metabolism is vital for brain function. Previous work in cultured cells has shown that a number of psychotropic drugs inhibit the activity of 7-dehydrocholesterol reductase (DHCR7), an enzyme that catalyzes the final steps in cholesterol biosynthesis. This leads to the accumulation of 7-dehydrocholesterol (7DHC), a molecule that gives rise to oxysterols, vitamin D, and atypical neurosteroids. We examined levels of cholesterol and the cholesterol precursors desmosterol, lanosterol, 7DHC and its isomer 8-dehydrocholesterol (8DHC), in blood samples of 123 psychiatric patients on various antipsychotic and antidepressant drugs, and 85 healthy controls, to see if the observations in cell lines hold true for patients as well...
February 12, 2017: Schizophrenia Research
Connor R Lamberson, Hubert Muchalski, Kari B McDuffee, Keri A Tallman, Libin Xu, Ned A Porter
The free radical chain autoxidation of cholesterol and the oxidation products formed, i.e. oxysterols, have been the focus of intensive study for decades. The peroxidation of sterol precursors to cholesterol such as 7-dehydrocholesterol (7-DHC) and desmosterol as well as their oxysterols has received less attention. The peroxidation of these sterol precursors can become important under circumstances in which genetic conditions or exposures to small molecules leads to an increase of these biosynthetic intermediates in tissues and fluids...
February 5, 2017: Chemistry and Physics of Lipids
Deirdre A Costello, Valerie A Villareal, Priscilla L Yang
Hepatitis C virus (HCV) uniquely affects desmosterol homeostasis by increasing its intracellular abundance and affecting its localization. These effects are important for productive viral replication because the inhibition of desmosterol synthesis has an antiviral effect that can be rescued by the addition of exogenous desmosterol. Here, we use subgenomic replicons to show that desmosterol has a major effect on the replication of HCV JFH1 RNA. Fluorescence recovery after photobleaching (FRAP) experiments performed with synthetic supported lipid bilayers demonstrate that the substitution of desmosterol for cholesterol significantly increases the lipid bilayer fluidity, especially in the presence of saturated phospholipids and ceramides...
November 11, 2016: ACS Infectious Diseases
L Baila-Rueda, A Cenarro, I Lamiquiz-Moneo, R Mateo-Gallego, A M Bea, S Perez-Calahorra, V Marco-Benedi, F Civeira
Some oxysterols are precursors of bile acid synthesis and play an important role in cholesterol homeostasis. However, if they are involved in the pathogeny of genetic hypercholesterolemia has not been previously explored. We have studied non-cholesterol sterol markers of cholesterol synthesis (lanosterol and desmosterol) and oxysterols (7α-hydroxy-4-cholesten-3-one, 24S-hydroxycholesterol and 27-hydroxycholesterol) in 200 affected subjects with primary hypercholesterolemia of genetic origin, negative for mutations in LDLR, APOB, PCSK9 and APOE genes (non-FH GH) and 100 normolipemic controls...
May 2017: Journal of Steroid Biochemistry and Molecular Biology
Tamara Gojkovic, Sandra Vladimirov, Vesna Spasojevic-Kalimanovska, Aleksandra Zeljkovic, Jelena Vekic, Dimitra Kalimanovska-Ostric, Ivana Djuricic, Sladjana Sobajic, Zorana Jelic-Ivanovic
BACKGROUND: Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization...
March 1, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
Matthew Peach, Ren Xu, Dan Fitzpatrick, Lisa Hamilton, Ransi Somaratne, Robert Scott, Scott M Wasserman, C Stephen Djedjos
The effects of cholesterol-lowering drugs, including those that reduce cholesterol synthesis (statins) and those that reduce cholesterol absorption (ezetimibe), on cholesterol absorption and synthesis are well understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a novel class of cholesterol-lowering drugs that robustly reduce LDL-cholesterol (LDL-C), but little is known about their effects on cholesterol absorption and synthesis. We evaluated how treatment with evolocumab, a fully human monoclonal IgG2 antibody to PCSK9, affects markers of cholesterol synthesis and absorption by measuring these markers in patients from an evolocumab clinical trial...
December 2016: Journal of Lipid Research
Inci Kazkayasi, Muhammad-Al-Mustafa Ismail, Cristina Parrado-Fernandez, Ingemar Björkhem, Can Pekiner, Serdar Uma, Angel Cedazo-Minguez, Nihan Burul-Bozkurt
Several studies demonstrated that Diabetes mellitus (DM) enhances the risk for Alzheimer's disease (AD). Although hyperglycemia and perturbed function of insulin signaling have been proposed to contribute to AD pathogenesis, the molecular mechanisms behind this association is not clear yet. Seladin-1 is an enzyme catalyzing the last step in cholesterol biosynthesis converting desmosterol to cholesterol. The neuroprotective function of seladin-1 has gained interest in AD research recently. Seladin-1 has anti-apoptotic properties and regulates the expression of β-secretase (BACE-1)...
October 28, 2016: Neuroscience Letters
Oliver Weingärtner, Ivan Bogeski, Carsten Kummerow, Stephan H Schirmer, Constanze Husche, Tim Vanmierlo, Gudrun Wagenpfeil, Markus Hoth, Michael Böhm, Dieter Lütjohann, Ulrich Laufs
This double-blind, randomized, placebo-controlled, cross-over intervention-study was conducted in healthy volunteers to evaluate the effects of plant sterol ester supplemented margarine on cholesterol, non-cholesterol sterols and oxidative stress in serum and monocytes. Sixteen volunteers, average age 34 years, with no or mild hypercholesterolemia were subjected to a 4 week period of daily intake of 3g plant sterols per day supplied via a supplemented margarine on top of regular eating habits. After a wash-out period of one week, volunteers switched groups...
May 2017: Journal of Steroid Biochemistry and Molecular Biology
Christine Vianey-Saban, Cécile Acquaviva, David Cheillan, Sophie Collardeau-Frachon, Laurent Guibaud, Cécile Pagan, Magali Pettazzoni, Monique Piraud, Antonin Lamazière, Roseline Froissart
Inborn errors of metabolism (IEMs) that present with abnormal imaging findings in the second half of pregnancy are mainly lysosomal storage disorders (LSDs), cholesterol synthesis disorders (CSDs), glycogen storage disorder type IV (GSD IV), peroxisomal disorders, mitochondrial fatty acid oxidation defects (FAODs), organic acidurias, aminoacidopathies, congenital disorders of glycosylation (CDGs), and transaldolase deficiency. Their biological investigation requires fetal material. The supernatant of amniotic fluid (AF) is useful for the analysis of mucopolysaccharides, oligosaccharides, sialic acid, lysosphingolipids and some enzyme activities for LSDs, 7- and 8-dehydrocholesterol, desmosterol and lathosterol for CSDs, acylcarnitines for FAODs, organic acids for organic acidurias, and polyols for transaldolase deficiency...
September 2016: Journal of Inherited Metabolic Disease
R O Pinho, D M A Lima, H H Shiomi, J B Siqueira, C O Silveira, V R Faria, P S Lopes, S E F Guimarães, J D Guimarães
The objective of this study was to investigate the effect of cyclodextrin-loaded cholesterol conjugates addition to freezing extenders on plasma membrane viability of frozen-thawed spermatozoa of the Piau swine breed. Twenty semen samples were used from five males. The freezing extender was based on lactose-egg yolk extender, added to 2% glycerol, 3% dimethylacetamide. The addition of cyclodextrin-loaded cholesterol conjugates was performed after centrifugation, when semen was diluted with the cooling extender...
August 2016: Cryobiology
Valerie A Villareal, Dan Fu, Deirdre A Costello, Xiaoliang Sunney Xie, Priscilla L Yang
Hepatitis C virus (HCV) increases intracellular desmosterol without affecting the steady-state abundance of other sterols, and the antiviral activity of inhibitors of desmosterol synthesis is suppressed by the addition of exogenous desmosterol. These observations suggest a model in which desmosterol has a specific function, direct or indirect, in HCV replication and that HCV alters desmosterol homeostasis to promote viral replication. Here, we use stimulated Raman scattering (SRS) microscopy in combination with isotopically labeled sterols to show that HCV causes desmosterol to accumulate in lipid droplets that are closely associated with the viral NS5A protein and that are visually distinct from the broad distribution of desmosterol in mock-infected cells and the more heterogeneous and disperse lipid droplets to which cholesterol traffics...
July 15, 2016: ACS Chemical Biology
Hye-Young H Kim, Zeljka Korade, Keri A Tallman, Wei Liu, C David Weaver, Karoly Mirnics, Ned A Porter
A small library of pharmacologically active compounds (the NIH Clinical Collection) was assayed in Neuro2a cells to determine their effect on the last step in the biosynthesis of cholesterol, the transformation of 7-dehydrocholesterol (7-DHC) to cholesterol promoted by 7-dehydrocholesterol reductase, DHCR7. Of some 727 compounds in the NIH Clinical Collection, over 30 compounds significantly increased 7-DHC in Neuro2a cells when assayed at 1 μM. Active compounds that increased 7-DHC with a Z-score of +3 or greater generally gave rise to modest decreases in desmosterol and increases in lanosterol levels...
May 16, 2016: Chemical Research in Toxicology
Valerio Leoni, Thomas Nury, Anne Vejux, Amira Zarrouk, Claudio Caccia, Meryam Debbabi, Agnès Fromont, Randa Sghaier, Thibault Moreau, Gérard Lizard
In multiple sclerosis (MS) a process of white matter degradation leading to demyelination is observed. Oxidative stress, inflammation, apoptosis, necrosis and/or autophagy result together into a progressive loss of oligodendrocytes. 7-ketocholesterol (7KC), found increased in the cerebrospinal fluid of MS patients, triggers a rupture of RedOx homeostasis associated with mitochondrial dysfunctions, aptoptosis and autophagy (oxiapoptophagy) in cultured murine oligodendrocytes (158N). α-tocopherol is able to mild the alterations induced by 7KC partially restoring the cellular homeostasis...
May 2017: Journal of Steroid Biochemistry and Molecular Biology
Qian Zhao, Chao Qian, Xin-Zhi Chen
A new highly stereoselective construction of the side chain of the C-24 and C-25 oxysterols has been achieved by using desmosterol acetate as the starting material and an improved Sharpless catalytic asymmetric dihydroxylation with 100% d.e. (diastereomeric excess) as the key step. The result is much better than the usual asymmetric dihydroxylation procedure. t-Butyl nitrite/2,2,6,6-tetramethylpiperidine N-oxyl radical/FeCl3 catalyst system was developed to activate molecular oxygen for the aerobic oxidation of 24-hydroxycholesterol and the 24-ketocholesterol was obtained in 86...
May 2016: Steroids
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