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Bernhard H Monien, Benjamin Sachse, Walter Meinl, Klaus Abraham, Alfonso Lampen, Hansruedi Glatt
Furfuryl alcohol (FFA) is a heat-induced food contaminant. Conversion by sulfotransferases (SULT) yields 2-sulfoxymethylfuran, which is prone to react with DNA and proteins. In order to monitor the internal FFA exposure we developed a technique for the mass spectrometric quantification of the adduct N-((furan-2-yl)methyl)-valine (FFA-Val) after cleavage from the N-termini of hemoglobin. In the current study the method was applied to investigate the influence of different SULT forms on the adduct formation in wild-type mice and three genetically modified mouse models treated with FFA...
June 13, 2018: Toxicology Letters
Weihua Jin, Shuai Li, Jiale Chen, Bing Liu, Jie Li, Xueliang Li, Fuming Zhang, Robert J Linhardt, Weihong Zhong
Heparan sulfate (HS), is a glycosaminoglycan (GAG) involved in various biological processes, including blood coagulation, wound healing and embryonic development. HS 3-O-sulfotransferases (3-OST), which transfer the sulfo group to the 3-hydroxyl group of certain glucosamine residues, is a key enzyme in the biosynthesis of a number of biologically important HS chains. The 3-OST-1 isoform is one of the 7 known 3-OST isoforms and is important for the biosynthesis of anticoagulant HS chains. In this study, we cloned 3-OST-1 from the rat brain by reverse transcription-polymerase chain reaction (RT-PCR)...
June 9, 2018: Protein Expression and Purification
Tarsis F Gesteira, Vivien J Coulson-Thomas
Heparan sulfate (HS) is a sulfated polysaccharide that plays a key role in morphogenesis, physiology and pathogenesis. The biosynthesis of HS takes place in the Golgi apparatus by a group of enzymes that polymerize, epimerize and sulfate the sugar chain. This biosynthetic process introduces varying degrees of sulfate substitution, which are tightly regulated and directly dictate binding specificity to different cytokines, morphogens and growth factors. Here we report the use of molecular dynamics simulations to investigate the dynamics of substrate recognition of two glycosaminoglycan (GAG) sulfotransferases, N-deacetylase-N-sulfotransferase and 2-O-sulfotransferase to the HS chain during the biosynthetic process...
June 6, 2018: Glycobiology
Zheng Zhao, Qingyan Wei, Weiwei Hua, Yunxin Liu, Xiang Liu, Yubing Zhu
Acetaminophen (APAP) hepatotoxicity remains the leading cause of drug-induced liver injury due to the lack of safe and effective therapeutic agents. Berberine (BBR) is a natural alkaloid derived from traditional medicine Rhizoma Coptidis and possesses various pharmacological properties. The aim of this study was to explore the hepatoprotective effects and underlying mechanisms of BBR on APAP-induced hepatotoxicity. Our results indicated that BBR pretreatment significantly ameliorated APAP-induced hepatic pathological abnormalities and attenuated the elevations of serum aminotransferases and liver/body weight ratio...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Sarah Dubaisi, Kathleen G Barrett, Hailin Fang, Jorge Guzman-Lepe, Alejandro Soto-Gutierrez, Thomas A Kocarek, Melissa Runge-Morris
Cytosolic sulfotransferases (SULTs) are expressed during early life and therefore metabolize endogenous and xenobiotic chemicals during development. Little is currently known about the regulation of individual SULTs in the developing human liver. We characterized SULT expression in primary cultures of human fetal hepatocytes and the HepaRG model of liver cell differentiation. SULT1A1 (transcript variants 1 - 4), SULT1C2, SULT1C4, SULT1E1, and SULT2A1 were the most abundant transcripts in human fetal hepatocytes...
June 1, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Heidi Laderoute, Christine Bone, E James Squires
Porcine sulfotransferase 2A1 (pSULT2A1) is a key enzyme involved in the testicular and hepatic sulfoconjugation of steroids such as dehydroepiandrosterone (DHEA) and potentially androstenone. This latter steroid is a major cause of boar taint, which is an unpleasant off-odour and off-flavour in pork from male pigs. Sulfotransferase 2B1 (pSULT2B1) may also be important, although no direct evidence exists for its involvement in sulfoconjugation of steroids. The purpose of this study was to investigate the sulfoconjugation activity of human and porcine sulfotransferases towards DHEA and androstenone...
May 22, 2018: Steroids
Erin N Jackson, Laura Rowland-Faux, Margaret O James, Charles E Wood
Sulfonation is a major pathway of estrogen biotransformation with a role in regulating estrogen homeostasis in humans and sheep. Previous in vitro studies found that triclosan is an especially potent competitive inhibitor of ovine placental estrogen sulfotransferase, with Kic of <0.1 nM. As the placenta is the main organ responsible for estrogen synthesis in pregnancy in both women and sheep, and the liver is another site of estrogen biotransformation, this study examined the effects of triclosan exposure of pregnant ewes on placental and hepatic sulfotransferase activity...
May 14, 2018: Toxicology Letters
Paul A Foster, Jonathan Wolf Mueller
Sulfation and desulfation pathways represent highly dynamic ways of shuttling, repressing and re-activating steroid hormones, thus controlling their immense biological potency at the very heart of endocrinology. This theme currently experiences growing research interest from various sides, including, but not limited to, novel insights about PAPS synthase and sulfotransferase function and regulation, novel analytics for steroid conjugate detection and quantification. Within this review, we will also define how sulfation pathways are ripe for drug development strategies, which have translational potential to treat a number of conditions, including chronic inflammatory diseases and steroid-dependent cancers...
May 15, 2018: Journal of Molecular Endocrinology
Barbara E Stopschinski, Brandon B Holmes, Gregory M Miller, Victor A Manon, Jaime Vaquer-Alicea, William L Prueitt, Linda C Hsieh-Wilson, Marc I Diamond
Transcellular propagation of protein aggregate "seeds" has been proposed to mediate the progression of neurodegenerative diseases in tauopathies and α-synucleinopathies. We previously reported that tau and α-synuclein aggregates bind heparan sulfate proteoglycans (HSPGs) on the cell surface, promoting cellular uptake and intracellular seeding. However, the specificity and binding mode of these protein aggregates to HSPGs remain unknown. Here, we measured direct binding to modified heparins to determine the size and sulfation requirements for tau, α-synuclein, and β-amyloid (Aβ) aggregate binding to glycosaminoglycans (GAGs)...
May 11, 2018: Journal of Biological Chemistry
Farhad Nejat, Hossein Aghamollaei, Shiva Pirhadi, Khosrow Jadidi, Mohammad Amin Nejat
Macular corneal dystrophy (MCD) is an autosomal recessive hereditary disease. In most cases, various mutations in carbohydrate sulfotransferase 6 (CHST6) gene are the main cause of MCD. These mutations lead to a defect in keratan sulfate synthesis. Retinitis pigmentosa (RP) is another eye disorder with nyctalopia as its common symptom. It has been shown that more than 65 genes have been implicated in different forms of RP. Herein, we report on a 9-member family with 2 girls and 5 boys. Both parents, one of the girls and one of the boys had normal eye vision and another boy had keratoconus...
March 2018: Iranian Journal of Medical Sciences
Jonathan W Mueller, Jan Idkowiak, Tarsis F Gesteira, Cecilia Vallet, Rebecca Hardman, Johannes van den Boom, Vivek Dhir, Shirley K Knauer, Edina Rosta, Wiebke Arlt
The high-energy sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS), generated by human PAPS synthase isoforms PAPSS1 and PAPSS2, is required for all human sulfation pathways. Sulfotransferase SULT2A1 uses PAPS for sulfation of the androgen precursor dehydroepiandrosterone (DHEA), thereby reducing downstream activation of DHEA to active androgens. Human PAPSS2 mutations manifest with undetectable DHEA sulfate, androgen excess and metabolic disease, suggesting that ubiquitous PAPSS1 cannot compensate for deficient PAPSS2 in supporting DHEA sulfation...
May 9, 2018: Journal of Biological Chemistry
Fei Shen, Hong-Mei Wen, Chen-Xiao Shan, An Kang, Bang Dong, Chuan Chai, Ji-Yun Zhang, Qi Zhang, Wei Li
Liguzinediol (2,5-dihydroxymethyl-3,6-dimethylpyrazine, LZDO) is a potential agent for the low-risk treatment of heart failure. 2-N-acetylcysteine-LZDO (2-NAC-LZDO) and 2-cysteine-LZDO (2-Cys-LZDO) are major LZDO metabolites found in the pharmacokinetic studies of rats and beagle dogs. To elucidate the biotransformation pathway and related enzymes, an incubation system with 3'-phosphoadenosine-5'-phosphosulfate (PAPS) as a cofactor and N-acetylcysteine (NAC) as a trapping agent was established using liver cytosol...
May 1, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Ngoc Thy Nguyen, Romain R Vivès, Magali Torres, Vincent Delauzun, Els Saesen, Véronique Roig-Zamboni, Hugues Lortat-Jacob, Pascal Rihet, Yves Bourne
The HS3ST3A1/B1 genes encode two homologous 3-O-sulfotransferases involved in the late modification step during heparan sulfate (HS) biosynthesis. In addition to the SNPs rs28470223 (C > T) in the promoter region of both HS3ST3A1 and rs62636623 (Gly/Arg) in the stem region of HS3ST3B1, three missense mutations (rs62056073, rs61729712 and rs9906590) located within the catalytic sulfotransferase domain of 3-OST-B1 are linked and associated to P. falciparum parasitaemia. To ascertain the functional effects of these SNP associations, we investigated the regulatory effect of rs28470223 and characterized the enzymatic activity of the missense SNP rs61729712 (Ser279Asn) localized at proximity of the substrate binding cleft...
April 28, 2018: Glycobiology
Fransiska Malfait
The Ehlers-Danlos Syndromes comprise a heterogeneous group of rare monogenic conditions that are characterized by joint hypermobility, skin and vascular fragility and generalized connective tissue friability. The latest classification recognizes 13 clinical subtypes, with mutations identified in 19 different genes. Besides defects in fibrillar collagens (collagen types I, III and V), their modifying enzymes (ADAMTS-2, lysylhydroxylase 1 (LH1)), and molecules involved in collagen folding (FKBP22), defects have recently been identified in other constituents of the extracellular matrix (e...
April 27, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Ahsan F Bairam, Mohammed I Rasool, Fatemah A Alherz, Maryam S Abunnaja, Amal A El Daibani, Katsuhisa Kurogi, Ming-Cheh Liu
Sulfoconjugation has been shown to be critically involved in the metabolism of acetaminophen (APAP), morphine, tapentadol and O-desmethyl tramadol (O-DMT). The objective of this study was to investigate the effects of single nucleotide polymorphisms (SNPs) of human SULT1A3 and SULT1A4 genes on the sulfating activity of SULT1A3 allozymes toward these analgesic compounds. Twelve non-synonymous coding SNPs (cSNPs) of SULT1A3/SULT1A4 were investigated, and the corresponding cDNAs were generated by site-directed mutagenesis...
April 26, 2018: Archives of Biochemistry and Biophysics
Fatemah A Alherz, Amal A El Daibani, Ahsan F Bairam, Maryam S Abunnaja, Mohammed I Rasool, Katsuhisa Kurogi, Yoichi Sakakibara, Masahito Suiko, Ming-Cheh Liu
Sulfated cholesterol, like its unsulfated counterpart, is known to be biologically active and serves a myriad of biochemical/physiological functions. Of the thirteen human cytosolic sulfotransferases (SULTs), SULT2B1b has been reported as the main enzyme responsible for the sulfation of cholesterol. As such, SULT2B1b may play the role as a key regulator of cholesterol metabolism. Variations in the sulfating activity of SULT2B1b may affect the sulfation of cholesterol and, consequently, the related physiological events...
April 25, 2018: Journal of Biochemistry
Yan Yin, Adam Wang, Li Feng, Yu Wang, Hong Zhang, Ivy Zhang, Brent M Bany, Liang Ma
To prepare for embryo implantation, the uterus must undergo a series of reciprocal interactions between the uterine epithelium and the underlying stroma, which are orchestrated by ovarian hormones. During this process, multiple signaling pathways are activated to direct cell proliferation and differentiation, which render the uterus receptive to the implanting blastocysts. One important modulator of these signaling pathways is the cell surface and extracellular matrix macromolecules, heparan sulfate proteoglycans (HSPGs)...
June 1, 2018: Endocrinology
Takehiko Shimohira, Katsuhisa Kurogi, Ming-Cheh Liu, Masahito Suiko, Yoichi Sakakibara
Members of the cytosolic sulfotransferase (SULT) SULT2A subfamily are known to be critically involved in the homeostasis of steroids and bile acids. SULT2A8, a 7α-hydroxyl bile acid-preferring mouse SULT, has been identified as the major enzyme responsible for the mouse-specific 7-O-sulfation of bile acids. Interestingly, SULT2A8 lacks a conservative catalytic His residue at position 99th. The catalytic mechanism underlying the SULT2A8-mediated 7-O-sulfation of bile acids thus remained unclear. In this study, we performed a mutational analysis in order to gain insight into this yet-unresolved issue...
April 24, 2018: Bioscience, Biotechnology, and Biochemistry
Mackenzie J Dickson, Candice L Hager, Ahmad Al-Shaibi, Porsha Q Thomas, Lance H Baumgard, Jason W Ross, Aileen F Keating
Environmental conditions that impede heat dissipation and increase body temperature cause heat stress (HS). The study objective was to evaluate impacts of HS on the follicular phase of the estrous cycle. Postpubertal gilts (126.0 ± 21.6 kg) were orally administered altrenogest to synchronize estrus, and subjected to either 5 d of thermal-neutral (TN; 20.3 ± 0.5 °C; n = 6) or cyclical HS (25.4 - 31.9 °C; n = 6) conditions during the follicular phase preceding behavioral estrus. On d 5, blood samples were obtained, gilts were euthanized, and ovaries collected...
June 4, 2018: Journal of Animal Science
Maryam S Abunnaja, Fatemah A Alherz, Amal A El Daibani, Ahsan F Bairam, Mohammed Ibrahim Rasool, Saud A Gohal, Katsuhisa Kurogi, Yoichi Sakakibara, Masahito Suiko, Ming-Cheh Liu
The cytosolic sulfotransferase (SULT) SULT2A1 is known to mediate the sulfation of dehydroepiandrosterone (DHEA) as well as some other hydroxysteroids such as pregnenolone. The present study was designed to investigate how genetic polymorphisms of the human SULT2A1 gene may affect the sulfation of DHEA and pregnenolone. Online databases were systematically searched to identify human SULT2A1 single nucleotide polymorphisms (SNPs). Of the 98 SULT2A1 non-synonymous coding SNPs identified, seven were selected for further investigation...
April 19, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
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