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https://www.readbyqxmd.com/read/28964935/new-chemotype-of-selective-and-potent-inhibitors-of-human-delta-24-dehydrocholesterol-reductase
#1
Christoph Müller, Sandra Hemmers, Nicholas Bartl, Alois Plodek, Andreas Körner, Valbona Mirakaj, Martin Giera, Franz Bracher
The enzyme Δ(24)-dehydrocholesterol reductase (DHCR24) catalyzes the reduction of the Δ(24)-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...
September 12, 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
#2
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
#3
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
#4
Piia Simonen, Jukka Lehtonen, Anna-Maija Lampi, Vieno Piironen, Ulf-Håkan Stenman, Markku Kupari, Helena Gylling
BACKGROUND: Amiodarone is an effective and widely used antiarrhythmic drug with many possible adverse effects including hypercholesterolemia 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...
September 1, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28807695/doxorubicin-enhances-oxysterol-levels-resulting-in-a-lxr-mediated-upregulation-of-cardiac-cholesterol-transporters
#5
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 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28665796/contamination-of-pine-and-birch-wood-dust-with-microscopic-fungi-and-determination-of-its-sterol-contents
#6
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
https://www.readbyqxmd.com/read/28657349/a-new-triterpene-ester-and-other-chemical-constituents-from-the-aerial-parts-of-anodendron-paniculatum-and-their-cytotoxic-activity
#7
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
https://www.readbyqxmd.com/read/28446672/cellular-cholesterol-facilitates-the-postentry-replication-cycle-of-herpes-simplex-virus-1
#8
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
https://www.readbyqxmd.com/read/28365392/effects-of-seaweed-sterols-fucosterol-and-desmosterol-on-lipid-membranes
#9
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
https://www.readbyqxmd.com/read/28276904/sterols-in-infant-formulas-validation-of-a-gas-chromatographic-method
#10
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
https://www.readbyqxmd.com/read/28202290/effect-of-psychotropic-drug-treatment-on-sterol-metabolism
#11
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...
September 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28174017/propagation-rate-constants-for-the-peroxidation-of-sterols-on-the-biosynthetic-pathway-to-cholesterol
#12
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...
October 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/27933788/desmosterol-increases-lipid-bilayer-fluidity-during-hepatitis-c-virus-infection
#13
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
https://www.readbyqxmd.com/read/27769814/bile-acid-synthesis-precursors-in-subjects-with-genetic-hypercholesterolemia-negative-for-ldlr-apob-pcsk9-apoe-mutations-association-with-lipids-and-carotid-atherosclerosis
#14
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
https://www.readbyqxmd.com/read/27718480/can-non-cholesterol-sterols-and-lipoprotein-subclasses-distribution-predict-different-patterns-of-cholesterol-metabolism-and-statin-therapy-response
#15
COMPARATIVE STUDY
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
https://www.readbyqxmd.com/read/27707817/effect-of-evolocumab-on-cholesterol-synthesis-and-absorption
#16
RANDOMIZED CONTROLLED TRIAL
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
https://www.readbyqxmd.com/read/27639960/lack-of-insulin-results-in-reduced-seladin-1-expression-in-primary-cultured-neurons-and-in-cerebral-cortex-of-stz-induced-diabetic-rats
#17
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
https://www.readbyqxmd.com/read/27473562/plant-sterol-ester-diet-supplementation-increases-serum-plant-sterols-and-markers-of-cholesterol-synthesis-but-has-no-effect-on-total-cholesterol-levels
#18
RANDOMIZED CONTROLLED TRIAL
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
https://www.readbyqxmd.com/read/27393412/antenatal-manifestations-of-inborn-errors-of-metabolism-biological-diagnosis
#19
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
https://www.readbyqxmd.com/read/27393245/effect-of-cyclodextrin-loaded-cholesterol-conjugates-on-plasma-membrane-viability-of-piau-swine-breed-frozen-thawed-spermatozoa
#20
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
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