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Seda Karabulut, Özlem Aksünger, Can Ata, Yusuf Sağıroglu, İlknur Keskin
Fertilization problems are the major problems that may be faced in 30-55% of the patients during an intracytoplasmic sperm injection (ICSI) cycle. A successful oocyte activation depends on factors related to both sperm and oocyte, and one of the important factors that mediates the process is Ca2+ concentration within the oocyte. Artificial oocyte activation (AOA) is a method used for fertilization problems that commonly involve the usage of Ca2+ ionophores and is usually used in problems such as total fertilization failure (TFF) and globozoospermia...
April 5, 2018: Systems Biology in Reproductive Medicine
Siou-Huei Wang, Han-Jen Lin, Yuan-Yu Lin, Yu-Jen Chen, Yu-Hui Pan, Cheng-Ting Tung, Harry John Mersmann, Shih-Torng Ding
During avian embryonic development, endodermal epithelial cells (EECs) absorb yolk through the yolk sac membrane. Sterol O-acyltransferase (SOAT) is important for esterification and yolk lipid utilization during development. Because the major enzyme for yolk sac membrane cholesteryl ester synthesis is SOAT1, we cloned the avian SOAT1 promoter and elucidated the cellular functions of SOAT1. Treatments with either glucagon, isobutylmethylxanthine (IBMX), an adenylate cyclase activator (forskolin), a cAMP analog (dibutyryl-cAMP), or a low glucose concentration all increased SOAT1 mRNA accumulation in EECs from Japanese quail, suggesting that SOAT1 is regulated by nutrients and hormones through a cAMP-dependent pathway...
2017: PloS One
Gary Grosser, Josefine Bennien, Alberto Sánchez-Guijo, Katharina Bakhaus, Barbara Döring, Michaela Hartmann, Stefan A Wudy, Joachim Geyer
The sodium-dependent organic anion transporter SOAT/Soat shows highly specific transport activity for sulfated steroids. SOAT substrates identified so far include dehydroepiandrosterone sulfate, 16α-hydroxydehydroepiandrosterone sulfate, estrone-3-sulfate, pregnenolone sulfate, 17β-estradiol-3-sulfate, and androstenediol sulfate. Apart from these compounds, many other sulfated steroids occur in mammals. Therefore, we aimed to expand the substrate spectrum of SOAT and analyzed the SOAT-mediated transport of eight different sulfated steroids by combining in vitro transport experiments in SOAT-transfected HEK293 cells with LC-MS/MS analytics of cell lysates...
September 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
Katharina Bakhaus, Daniela Fietz, Sabine Kliesch, Wolfgang Weidner, Martin Bergmann, Joachim Geyer
Sodium-dependent organic anion transporter (SOAT) represents a membrane transporter specific for sulfated steroid hormones, which are supposed to participate in the regulation of reproductive processes. In man, SOAT shows predominant mRNA expression in the testis and here was localized to primary spermatocytes. SOAT mRNA expression is significantly downregulated in different disorders of spermatogenesis, including hypospermatogenesis. The resulting decline of SOAT-mediated transport of sulfated steroids may participate in the impairment of functional spermatogenesis...
September 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
Josefine Bennien, Thomas Fischer, Joachim Geyer
Sulfo-conjugated steroid hormones, such as dehydroepiandrosterone sulfate (DHEAS), pregnenolone sulfate or estrone-3-sulfate are abundant in the body, but are biologically inactive at classical androgen and estrogen steroid receptors. However, after carrier-mediated import and de-conjugation by the steroid sulfatase, these compounds participate in the overall steroid regulation of reproductive organs. The sodium-dependent organic anion transporter SOAT, coded by the SLC10A6 gene, is specific for the transport of steroid sulfates and is highly expressed in testicular germ cells, including pachytene spermatocytes, secondary spermatocytes, and round spermatids...
September 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
S Rahbar, M G Novin, E Alizadeh, V Shahnazi, F Pashaei-Asl, Y A AsrBadr, L Farzadi, E Ebrahimie, M Pashaiasl
Spermatogenesis is proliferation and differentiation processes of stem spermatogonia into mature spermatozoa controlled by the genes responsible for transcription and post transcription levels. MicroRNAs (miRNA) are  the key factors during gene expression in RNA silencing and post-transcriptional regulation. They play main roles in regulation of early and late spermatogenesis, and reproduction. In this study, we investigate the role of miRNAs in infertile males.The patients were assigned to five groups based on semen analysis (n=55), including normozoospermic (N), moderate oligoasthenoteratozoospermic (MOAT), severe oligoasthenoteratozoospermic (SOAT), obstructive azoospermia (OA) and non-obstructive azoospermia (NOA)...
August 30, 2017: Cellular and Molecular Biology
Katharina Bakhaus, Josefine Bennien, Daniela Fietz, Alberto Sánchez-Guijo, Michaela Hartmann, Rosanna Serafini, Charles C Love, Andrei Golovko, Stefan A Wudy, Martin Bergmann, Joachim Geyer
The sodium-dependent organic anion transporter SOAT (gene name SLC10A6 in man and Slc10a6 in mice) is a plasma membrane transporter for sulfated steroids, which is highly expressed in germ cells of the testis. SOAT can transport biologically inactive sulfated steroids into specific target cells, where they can be reactivated by the steroid sulfatase (STS) to biologically active, unconjugated steroids known to regulate spermatogenesis. Significantly reduced SOAT mRNA expression was previously found in different forms of impaired spermatogenesis in man...
July 22, 2017: Journal of Steroid Biochemistry and Molecular Biology
Taichi Ohshiro, Keisuke Kobayashi, Mio Ohba, Daisuke Matsuda, Lawrence L Rudel, Takashi Takahashi, Takayuki Doi, Hiroshi Tomoda
Beauveriolide III (BeauIII) inhibited sterol O-acyltransferases 1 and 2 (SOAT1 and SOAT2), which are endoplasmic reticulum (ER) membrane proteins, in an enzyme-based assay, and selectively inhibited SOAT1 in a cell-based assay using SOAT1-/SOAT2-CHO cells. This discrepancy in SOAT inhibition by BeauIII was investigated. In the enzyme-based assay, BeauIII inhibited SOAT1 and SOAT2 to a similar extent using microsomes prepared from cells disrupted under the strongest sonication condition. In semi-intact SOAT1-/SOAT2-CHO cells prepared by a treatment with digitonin (plasma membrane permeabilized), BeauIII selectively inhibited SOAT1 (IC50; 5...
June 23, 2017: Scientific Reports
Richard Buendia, Monica Zambrano
BACKGROUND: Emerging evidence has shown a significant deficit in the control of hypertension (blood pressure <140/90 mmHg) among Hispanics or Latinos in about 65%. This study aims to determine the efficacy of the combination in fixed doses of olmesartan and amlodipine (20/5, 40/5, and 40/10 mg) in hypertensive patients treated in daily clinical practice by Colombian doctors. METHODS: This was an observational, retrospective, open-label, multi-center, non-comparative study...
April 26, 2017: BMC Research Notes
Arihiro Iwasaki, Takato Tadenuma, Shimpei Sumimoto, Taichi Ohshiro, Kaori Ozaki, Keisuke Kobayashi, Toshiaki Teruya, Hiroshi Tomoda, Kiyotake Suenaga
Biseokeaniamides A, B, and C (1-3), structurally novel sterol O-acyltransferase (SOAT) inhibitors, were isolated from an Okeania sp. marine cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Biseokeaniamide B (2) exhibited moderate cytotoxicity against human HeLa cancer cells, and compounds 1-3 inhibited both SOAT1 and SOAT2, not only at an enzyme level but also at a cellular level. Biseokeaniamides (1-3) are the first linear lipopeptides that have been shown to exhibit SOAT-inhibitory activity...
April 28, 2017: Journal of Natural Products
Palash Pal, Hardik P Gandhi, Ashish M Kanhed, Nirali R Patel, Niraj N Mankadia, Satish N Baldha, Mahesh A Barmade, Prashant R Murumkar, Mange Ram Yadav
A novel series of vicinal diaryl azole-urea derivatives were synthesized and evaluated for their potential to inhibit SOAT enzyme. Among the reported compounds, compound (12d) emerged as the most potent compound with an IC50 value of 2.43 μM. In polaxamer-407 induced lipoprotein lipase inhibition model, compound (12d) reduced triglyceride turnover in vivo. Compound (12d) also showed dose-dependent prevention of serum total cholesterol and prevention of LDL-C elevation at a dose of 30 mg/kg. Furthermore, compound (12d) showed potential to stop falling levels of serum HDL-C dose-dependently and improved the atherogenic index...
April 21, 2017: European Journal of Medicinal Chemistry
Nai-Yun Chang, Yen-Ju Chan, Shih-Torng Ding, Yen-Hua Lee, Wei-Chun HuangFu, I-Hsuan Liu
To elucidate whether Sterol O-acyltransferase (Soat) mediates the absorption and transportation of yolk lipids to the developing embryo, zebrafish soat1 and soat2 were cloned and studied. In the adult zebrafish, soat1 was detected ubiquitously while soat2 mRNA was detected specifically in the liver, intestine, brain and testis. Whole mount in situ hybridization demonstrated that both soat1 and soat2 expressed in the yolk syncytial layer, hatching gland and developing cardiovascular as well as digestive systems, suggesting that Soats may play important roles in the lipid trafficking and utilization during embryonic development...
2016: PloS One
Keisuke Kobayashi, Taichi Ohshiro, Hiroshi Tomoda, Feng Yin, Hai-Lei Cui, Pandurang V Chouthaiwale, Fujie Tanaka
Synthesis of new functionalized molecules and identification of biofunctional molecules can lead to the development of therapeutic leads and molecular tools for biomedical research. We have recently reported oxa-hetero-Diels-Alder reactions of enones with isatins to provide functionalized spirooxindole tetrahydropyran derivatives. Twenty-one compounds from the spirooxindole tetrahydropyran derivatives and related molecules were screened for inhibition of sterol O-acyltransferase (SOAT) isozymes SOAT1 and SOAT2...
December 15, 2016: Bioorganic & Medicinal Chemistry Letters
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...
September 2017: 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, Sung-Hak Kim, Jose Otero, Vinay 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...
November 1, 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
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