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Deborah Solomon, Meredith Lahl, Marian Soat, James Bena, Mark McClelland
No abstract text is available yet for this article.
August 2016: Nursing Management
Joachim Geyer, Katharina Bakhaus, Rita Bernhardt, Carina Blaschka, Yaser Dezhkam, Daniela Fietz, Gary Grosser, Katja Hartmann, Michaela F Hartmann, Jens Neunzig, Dimitrios Papadopoulos, Alberto Sánchez-Guijo, Georgios Scheiner-Bobis, Gerhard Schuler, Mazen Shihan, Christine Wrenzycki, Stefan A Wudy, Martin Bergmann
Sulfated steroid hormones, such as dehydroepiandrosterone sulfate or estrone-3-sulfate, have long been regarded as inactive metabolites as they cannot activate classical steroid receptors. Some of them are present in the blood circulation at quite high concentrations, but generally sulfated steroids exhibit low membrane permeation due to their hydrophilic properties. However, sulfated steroid hormones can actively be imported into specific target cells via uptake carriers, such as the sodium-dependent organic anion transporter SOAT, and, after hydrolysis by the steroid sulfatase (so-called sulfatase pathway), contribute to the overall regulation of steroid responsive organs...
July 5, 2016: Journal of Steroid Biochemistry and Molecular Biology
Feng Geng, Xiang Cheng, Xiaoning Wu, Ji Young Yoo, Chunming Cheng, Jeffrey Yunhua Guo, Xiaokui Mo, Peng Ru, Brian Hurwitz, Sunghak Kim, Jose Otero, Vinay K Puduvalli, Etienne Lefai, Jianjie Ma, Ichiro Nakano, Craig Horbinski, Balveen Kaur, Arnab Chakravarti, Deliang Guo
PURPOSE: Elevated lipogenesis regulated by sterol regulatory element-binding protein-1 (SREBP-1), a transcription factor playing a central role in lipid metabolism, is a novel characteristic of glioblastoma (GBM). The aim of this study was to identify effective approaches to suppress GBM growth by inhibition of SREBP-1. As SREBP activation is negatively regulated by endoplasmic reticulum (ER) cholesterol, we sought to determine whether suppression of sterol O-acyltransferase (SOAT), a key enzyme converting ER cholesterol to cholesterol esters (CE) to store in lipid droplets (LDs), effectively suppressed SREBP-1 and blocked GBM growth...
June 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Gary Grosser, Karl-Heinz Baringhaus, Barbara Döring, Werner Kramer, Ernst Petzinger, Joachim Geyer
The sodium-dependent organic anion transporter SOAT specifically transports sulfated steroid hormones and is supposed to play a role in testicular steroid regulation and male fertility. The present study aimed to identify novel specific SOAT inhibitors for further in vitro and in vivo studies on SOAT function. More than 100 compounds of different molecular structures were screened for inhibition of the SOAT-mediated transport of dehydroepiandrosterone sulfate in stably transfected SOAT-HEK293 cells. Twenty-five of these with IC50 values covering four orders of magnitude were selected as training set for 3D pharmacophore modelling...
June 15, 2016: Molecular and Cellular Endocrinology
Yuichi Masuda, Kazumasa Aoyama, Masahito Yoshida, Keisuke Kobayashi, Taichi Ohshiro, Hiroshi Tomoda, Takayuki Doi
Beauveriolides I and III, which are naturally occurring cyclodepsipeptides, have been reported to bind to sterol O-acyltransferase (SOAT), inhibiting its ability to synthesize cholesteryl esters. To facilitate an analysis of the binding site(s) of these compounds, we designed beauveriolide analogues 1a-d wherein the Leu or D-allo-Ile residue was replaced by photoreactive amino acids possessing methyldiazirine or trifluoromethyldiazirine in the side chains. The methyldiazirine moiety was installed by reaction of methyl ketones with liquid ammonia to provide imine intermediates, followed by treatment with hydroxylamine-O-sulfonic acid to provide the diaziridines...
July 1, 2016: Chemical & Pharmaceutical Bulletin
Ryuji Uchida, Kento Nakajyo, Keisuke Kobayashi, Taichi Ohshiro, Takeshi Terahara, Chiaki Imada, Hiroshi Tomoda
A new depsidone, named 7-chlorofolipastatin, and five known structurally related depsidones were isolated from the culture broth of the marine-derived fungus Aspergillus ungui NKM-007 by solvent extraction and HPLC using an octadecylsilyl column. The structure of 7-chlorofolipastatin was elucidated by various spectroscopic data including 1D and 2D NMR spectroscopy. 7-Chlorofolipastatin inhibited sterol O-acyltransferase (SOAT) 1 and 2 isozymes in cell-based and enzyme assays using SOAT1- and SOAT2-expressing Chinese hamster ovary (CHO) cells...
August 2016: Journal of Antibiotics
Christopher S Potter, Michael J Kern, Mary Ann Baybo, Nathanael D Pruett, Alan R Godwin, John P Sundberg, Alexander Awgulewitsch
The cholesterol-metabolizing enzyme sterol O-acetyltransferase (SOAT1) is implicated in an increasing number of biological and pathological processes in a number of organ systems, including the differentiation of the hair shaft. While the functional and regulatory mechanisms underlying these diverse functional roles remain poorly understood, the compartment of the hair shaft known as medulla, affected by mutations in Soat1, may serve as a suitable model for defining some of these mechanisms. A comparative analysis of mRNA and protein expression patterns of Soat1/SOAT1 and the transcriptional regulator Hoxc13/HOXC13 in postnatal skin of FVB/NTac mice indicated co-expression in the most proximal cells of the differentiating medulla...
December 2015: Experimental and Molecular Pathology
Adam M Lopez, Jen-Chieh Chuang, Kenneth S Posey, Taichi Ohshiro, Hiroshi Tomoda, Lawrence L Rudel, Stephen D Turley
In most organs, the bulk of cholesterol is unesterified, although nearly all possess a varying capability of esterifying cholesterol through the action of either sterol O-acyltransferase (SOAT) 1 or, in the case of hepatocytes and enterocytes, SOAT2. Esterified cholesterol (EC) carried in plasma lipoproteins is hydrolyzed by lysosomal acid lipase (LAL) when they are cleared from the circulation. Loss-of-function mutations in LIPA, the gene that encodes LAL, result in Wolman disease or cholesteryl ester storage disease (CESD)...
November 2015: Journal of Pharmacology and Experimental Therapeutics
Sonia Gulati, Dina Balderes, Christine Kim, Zhongmin A Guo, Lisa Wilcox, Estela Area-Gomez, Jamie Snider, Heimo Wolinski, Igor Stagljar, Juliana T Granato, Kelly V Ruggles, Joseph A DeGiorgis, Sepp D Kohlwein, Eric A Schon, Stephen L Sturley
A key component of eukaryotic lipid homeostasis is the esterification of sterols with fatty acids by sterol O-acyltransferases (SOATs). The esterification reactions are allosterically activated by their sterol substrates, the majority of which accumulate at the plasma membrane. We demonstrate that in yeast, sterol transport from the plasma membrane to the site of esterification is associated with the physical interaction of the major SOAT, acyl-coenzyme A:cholesterol acyltransferase (ACAT)-related enzyme (Are)2p, with 2 plasma membrane ATP-binding cassette (ABC) transporters: Aus1p and Pdr11p...
November 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Keisuke Kobayashi, Nobuaki Tsukasaki, Ryuji Uchida, Yuichi Yamaguchi, Hiroshi Tomoda
A new compound designated as clonoamide was isolated from a culture broth of the fungus Clonostachys sp. BF-0131 by solvent extraction, Diaion HP20 column chromatography, octadecylsilyl column chromatography and preparative HPLC as an inhibitor of sterol O-acyltransferase (SOAT). The structure of clonoamide was elucidated as 2-oxo-9E,11E-tridecandienyl acetamide by various spectral analyses including NMR. The compound inhibited SOAT1 and SOAT2 isozymes with IC50 values of 39 and 110 μm, respectively, in a cell-based assay using SOAT1- and SOAT2-expressing Chinese hamster ovary cells...
October 2015: Journal of Antibiotics
Gary Grosser, Barbara Döring, Bernhard Ugele, Joachim Geyer, Sabine E Kulling, Sebastian T Soukup
Soy isoflavones (IF) are phytoestrogens, which interact with estrogen receptors. They are extensively metabolized by glucuronosyltransferases and sulfotransferases, leading to the modulation of their estrogenic activity. It can be assumed that this biotransformation also has a crucial impact on the uptake of IF by active or passive cellular transport mechanisms, but little is known about the transport of IF phase II metabolites into the cell. Therefore, transport assays for phase II metabolites of daidzein (DAI) were carried out using HEK293 cell lines transfected with five human candidate carriers, i...
December 2015: Archives of Toxicology
Jennifer P Colwill, Colin O'Rourke, Lydia Booher, Marian Soat, Deborah Solomon, Nancy M Albert
PURPOSE: The aim of this study was to quantify clinical nurse specialist (CNS) work and determine if competencies are associated with personal characteristics, priorities, and quality outcomes. BACKGROUND: The work of a CNS is difficult to quantify. Nurse leaders need quantifiable data to understand the impact of CNS work. DESIGN: A prospective, single-center, correlational study with a convenience sample was conducted. SETTING AND SAMPLE: The study was conducted in a 1200-bed quaternary care medical center in Northeast Ohio, using CNSs...
November 2014: Clinical Nurse Specialist CNS
Maximillian A Rogers, Jay Liu, Bao-Liang Song, Bo-Liang Li, Catherine C Y Chang, Ta-Yuan Chang
Cholesterol is essential to the growth and viability of cells. The metabolites of cholesterol include: steroids, oxysterols, and bile acids, all of which play important physiological functions. Cholesterol and its metabolites have been implicated in the pathogenesis of multiple human diseases, including: atherosclerosis, cancer, neurodegenerative diseases, and diabetes. Thus, understanding how cells maintain the homeostasis of cholesterol and its metabolites is an important area of study. Acyl-coenzyme A:cholesterol acyltransferases (ACATs, also abbreviated as SOATs) converts cholesterol to cholesteryl esters and play key roles in the regulation of cellular cholesterol homeostasis...
July 2015: Journal of Steroid Biochemistry and Molecular Biology
Jivianne T Lee, Oswaldo H Escobar, Rabin Anouseyan, Agnieszka Janisiewicz, Edward Eivers, Keith E Blackwell, David B Keschner, Rohit Garg, Edith Porter
BACKGROUND: Airway secretions contain endogenous antimicrobial factors (AMFs) that contribute to the innate host defense of the respiratory tract. Antibacterial peptides as well as host-derived lipids including cholesteryl esters have been detected in maxillary lavage fluid. Sterol O-acyltransferase 1 (SOAT1) is a key enzyme in cholesteryl ester production. The purpose of this study is to determine if such intrinsic microbicidal molecules are acutely expressed within sinus tissue and to compare levels of expression between patients with and without chronic rhinosinusitis (CRS)...
November 2014: International Forum of Allergy & Rhinology
J Neunzig, A Sánchez-Guijo, A Mosa, M F Hartmann, J Geyer, S A Wudy, R Bernhardt
In many tissues sulfonated steroids exceed the concentration of free steroids and recently they were also shown to fulfill important physiological functions. While it was previously demonstrated that cholesterol sulfate (CS) is converted by CYP11A1 to pregnenolone sulfate (PregS), further conversion of PregS has not been studied in detail. To investigate whether a steroidogenic pathway for sulfonated steroids exists similar to the one described for free steroids, we examined the interaction of PregS with CYP17A1 in a reconstituted in-vitro system...
October 2014: Journal of Steroid Biochemistry and Molecular Biology
H Schweigmann, A Sánchez-Guijo, B Ugele, K Hartmann, M F Hartmann, M Bergmann, C Pfarrer, B Döring, S A Wudy, E Petzinger, J Geyer, G Grosser
16α-Hydroxy-dehydroepiandrosterone sulfate (16α-OH-DHEAS) mainly originates from the fetus and serves as precursor for placental estriol biosynthesis. For conversion of 16α-OH-DHEAS to estriol several intracellular enzymes are required. However, prior to enzymatic conversion, 16α-OH-DHEAS must enter the cells by carrier mediated transport. To identify these carriers, uptake of 16α-OH-DHEAS by the candidate carriers organic anion transporter OAT4, sodium-dependent organic anion transporter SOAT, Na(+)-taurocholate cotransporting polypeptide NTCP, and organic anion transporting polypeptide OATP2B1 was measured in stably transfected HEK293 cells by LC-MS-MS...
September 2014: Journal of Steroid Biochemistry and Molecular Biology
Richard Lathe, Alexandra Sapronova, Yuri Kotelevtsev
BACKGROUND: Aging is accompanied by increasing vulnerability to pathologies such as atherosclerosis (ATH) and Alzheimer disease (AD). Are these different pathologies, or different presentations with a similar underlying pathoetiology? DISCUSSION: Both ATH and AD involve inflammation, macrophage infiltration, and occlusion of the vasculature. Allelic variants in common genes including APOE predispose to both diseases. In both there is strong evidence of disease association with viral and bacterial pathogens including herpes simplex and Chlamydophila...
2014: BMC Geriatrics
Mark R Lafave, Larry Katz
CONTEXT: Health care professions have replaced traditional multiple choice tests or essays with structured and practical, performance-based examinations with the hope of eliminating rater bias and measuring clinical competence. OBJECTIVE: To establish the validity and reliability of the Standardized Orthopedic Assessment Tool (SOAT) as a measure of clinical competence of orthopaedic injury evaluation. DESIGN: Descriptive laboratory study. SETTING: University...
May 2014: Journal of Athletic Training
Daniela Fietz, Katharina Bakhaus, Britta Wapelhorst, Gary Grosser, Sabine Günther, Jörg Alber, Barbara Döring, Sabine Kliesch, Wolfgang Weidner, Christina E Galuska, Michaela F Hartmann, Stefan A Wudy, Martin Bergmann, Joachim Geyer
Sulfated steroid hormones are commonly considered to be biologically inactive metabolites, but may be reactivated by the steroid sulfatase into biologically active free steroids, thereby having regulatory function via nuclear androgen and estrogen receptors which are widespread in the testis. However, a prerequisite for this mode of action would be a carrier-mediated import of the hydrophilic steroid sulfate molecules into specific target cells in reproductive tissues such as the testis. In the present study we detected predominant expression of the Sodium-dependent Organic Anion Transporter (SOAT), the Organic Anion Transporting Polypeptide 6A1, and the Organic Solute Carrier Partner 1 in human testis biopsies...
2013: PloS One
Gary Grosser, Daniela Fietz, Sabine Günther, Katharina Bakhaus, Helene Schweigmann, Bernhard Ugele, Ralph Brehm, Ernst Petzinger, Martin Bergmann, Joachim Geyer
The sodium-dependent organic anion transporter SOAT is a member of the Solute Carrier Family SLC10. In man, this carrier is predominantly expressed in the testis and has transport activity for sulfoconjugated steroid hormones. Here, we report on cloning, expression analysis and functional characterization of the mouse Soat (mSoat) and compare its characteristics with the human SOAT carrier. Quantitative mRNA expression analysis for mSoat in male mice revealed very high expression in lung and further high expression in testis and skin...
November 2013: Journal of Steroid Biochemistry and Molecular Biology
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