Read by QxMD icon Read


K Hartmann, J Bennien, B Wapelhorst, K Bakhaus, V Schumacher, S Kliesch, W Weidner, M Bergmann, J Geyer, D Fietz
Within the human testis, large amounts of sulfated steroid hormones are produced. As shown in breast tissue and placenta, these might not only be excretion intermediates, but re-activated in target cells by steroid sulfatase (STS). This process is called sulfatase pathway and may play a pivotal role in para- and/or intracrine regulation by creating a local supply for steroid hormones. This requires a facilitated transport via uptake carriers and efflux transporters as these hydrophilic molecules cannot pass the cell membrane...
September 29, 2016: Histochemistry and Cell Biology
Masahito Suiko, Katsuhisa Kurogi, Takuyu Hashiguchi, Yoichi Sakakibara, Ming-Cheh Liu
The cytosolic sulfotransferases (SULTs) are Phase II detoxifying enzymes that mediate the sulfate conjugation of numerous xenobiotic molecules. While the research on the SULTs has lagged behind the research on Phase I cytochrome P-450 enzymes and other Phase II conjugating enzymes, it has gained more momentum in recent years. This review aims to summarize information obtained in several fronts of the research on the SULTs, including the range of the SULTs in different life forms, concerted actions of the SULTs and other Phase II enzymes, insights into the structure-function relationships of the SULTs, regulation of SULT expression and activity, developmental expression of SULTs, as well as the use of a zebrafish model for studying the developmental pharmacology/toxicology...
September 21, 2016: Bioscience, Biotechnology, and Biochemistry
Hansi Jia, Chiteng Zhang, Hansruedi Glatt, Yungang Liu
The standard procedure for the micronucleus test in cell lines requires a short exposure (≤0.5 cell cycle) to the test compounds followed by a long recovery (≥1.5 cell cycle), and in case of negative or equivocal results, a second test with extended exposure (≥2 cell cycles) without or with a recovery time. In general the two procedures are advantageous for detecting clastogens and aneugens, respectively. However, whether the recommended procedures apply to micronucleus tests with promutagens in cell lines genetically engineered for expressing biotransformation enzymes has not been identified...
September 15, 2016: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
Weiru Jiang, Xiangge Tian, Yan Wang, Zheng Sun, Peipei Dong, Chao Wang, Xiaokui Huo, Baojing Zhang, Shanshan Huang, Sa Deng, Xiaobo Wang, Xiaochi Ma
Melatonin (Mel) as an endogenous hormone, has been widely used in clinic for multiple therapeutic purposes. Further, the natural anthraquinones were widespread in various plants including herbs, foods, and some flavoring agents. The present work aims to evaluate the metabolic disorder of Mel caused by various common herbs and further identify their underlying mechanism. More importantly, the relationships between inhibitory activity and their structures were also investigated. Our results demonstrate that some herbs containing anthraquinone derivatives exhibited strong inhibition on Mel metabolism...
September 12, 2016: Toxicology Letters
Ruiming Guo, Luqing Pan, Pengfei Lin, Lei Zheng
This study aimed to investigate the detoxification responses, damage effects and biotransformation in scallop Chlamys farreri exposed to benzo[a]pyrene (BaP) (0.1, 1μg/L), chrysene (CHR) (0.1, 1μg/L) and BaP+CHR (0.1+0.1, 1+1μg/L) for 15days. Results demonstrated that BaP and CHR concentration (BaP<CHR) in tissues increased rapidly in a time and dose effect. The mRNA expression of aryl hydrocarbon receptor (AhR), cytochrome P450 1A1 (CYP1A1), CYP1B1, multidrug resistance protein 1 (MRP1/ABCC1), breast cancer resistance protein (BCRP/ABCG2) and P-glycoprotein (P-gp) were induced especially in the mixtures of BaP and CHR...
September 11, 2016: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
Arabella Young, Shin Foong Ngiow, Deborah S Barkauskas, Erin Sult, Carl Hay, Stephen J Blake, Qihui Huang, Jing Liu, Kazuyoshi Takeda, Michele W L Teng, Kris Sachsenmeier, Mark J Smyth
Preclinical studies targeting the adenosinergic pathway have gained much attention for their clinical potential in overcoming tumor-induced immunosuppression. Here, we have identified that co-blockade of the ectonucleotidase that generates adenosine CD73 and the A2A adenosine receptor (A2AR) that mediates adenosine signaling in leuokocytes, by using compound gene-targeted mice or therapeutics that target these molecules, limits tumor initiation, growth, and metastasis. This tumor control requires effector lymphocytes and interferon-γ, while antibodies targeting CD73 promote an optimal therapeutic response in vivo when engaging activating Fc receptors...
September 12, 2016: Cancer Cell
Carl M Hay, Erin Sult, Qihui Huang, Kathy Mulgrew, Stacy R Fuhrmann, Kelly A McGlinchey, Scott A Hammond, Raymond Rothstein, Jonathan Rios-Doria, Edmund Poon, Nick Holoweckyj, Nicholas M Durham, Ching Ching Leow, Gundo Diedrich, Melissa Damschroder, Ronald Herbst, Robert E Hollingsworth, Kris F Sachsenmeier
MEDI9447 is a human monoclonal antibody that is specific for the ectoenzyme CD73 and currently undergoing Phase I clinical trials. Here we show that MEDI9447 is a potent inhibitor of CD73 ectonucleotidase activity, with wide ranging immune regulatory consequences. MEDI9447 results in relief from adenosine monophosphate (AMP)-mediated lymphocyte suppression in vitro and inhibition of mouse syngeneic tumor growth in vivo. In contrast with other cancer immunotherapy agents such as checkpoint inhibitors or T-cell agonists, MEDI9447 drives changes in both myeloid and lymphoid infiltrating leukocyte populations within the tumor microenvironment of mouse models...
August 2016: Oncoimmunology
S X Hu
The hepatic activities of uridine diphosphate glucuronosyltransferase (UGT) and sulfotransferase (SULT) of male Ross 708 broiler chickens at the age of 1, 7, 14, 28, and 56 days and male Camborough-29 pigs at the age of 1 day and 2, 5, 10, and 20 weeks were investigated. Glucuronidation and sulfation of 4-nitrophenol were used to evaluate the activities. Porcine hepatic UGT and SULT activities were low at birth, peaked at around 5-10 weeks, and then declined. Both hepatic UGT and SULT activities of chickens were high at hatch and declined...
September 4, 2016: Journal of Veterinary Pharmacology and Therapeutics
Akihiro Yamamoto, Katsuhisa Kurogi, Isaac Thomas Schiefer, Ming-Yih Liu, Yoichi Sakakibara, Masahito Suiko, Ming-Cheh Liu
Dextrorphan, an active metabolite of the antitussive dextromethorphan, has been shown to be subjected to sulfation by several zebrafish cytosolic sulfotransferases (SULTs). We were interested in finding out which of the human SULT(s) is(are) capable of catalyzing the sulfation of dextrorphan, and to verify whether sulfation of dextrorphan may occur in cultured human cells and human organ cytosols. Data from the enzymatic assays showed that, of all thirteen known human SULTs, SULT1A3 displayed the strongest dextrorphan-sulfating activity...
2016: Biological & Pharmaceutical Bulletin
Ling Ye, Chuqi Hou, Shuwen Liu
Patients with human immunodeficiency virus (HIV) receive antiretroviral therapy (ART) through the use of antiretroviral drugs. A combination of at least three drugs that suppreses HIV replication is used as standard treatment, and this is often called "highly active antiretroviral therapy" (HAART). Virus resistance is less likely when three or more drugs are used. A complication of anti-HIV drugs has a complex pharmacokinetic profile which is involved with extensive metabolism and transport by drug metabolizing enzymes (e...
August 29, 2016: Current Topics in Medicinal Chemistry
Sarah Dubaisi, Hailin Fang, Thomas A Kocarek, Melissa Runge-Morris
Cytosolic sulfotransferase 1C3 (SULT1C3) is the least characterized of the three human SULT1C subfamily members. Originally identified as an orphan SULT by computational analysis of the human genome, we recently reported that SULT1C3 is expressed in human intestine and LS180 colorectal adenocarcinoma cells and is upregulated by agonists of peroxisome proliferator-activated receptor (PPAR) α and γ To determine the mechanism responsible for PPAR-mediated upregulation, we prepared reporter plasmids containing fragments of the SULT1C3 5'-flanking region...
November 2016: Molecular Pharmacology
Dong Woo Lee, Woo-Yeon Oh, Sang Hyun Yi, Bosung Ku, Moo-Yeal Lee, Yoon Hee Cho, Mihi Yang
Bisphenol A (BPA) has been widely used for manufacturing polycarbonate plastics and epoxy resins and has been extensively tested in animals to predict human toxicity. In order to reduce the use of animals for toxicity assessment and provide further accurate information on BPA toxicity in humans, we encapsulated Hep3B human hepatoma cells in alginate and cultured them in three dimensions (3D) on a micropillar chip coupled to a panel of metabolic enzymes on a microwell chip. As a result, we were able to assess the toxicity of BPA under various metabolic enzyme conditions using a high-throughput and micro assay; sample volumes were nearly 2,000 times less than that required for a 96-well plate...
September 30, 2016: Toxicology Letters
Katsuhisa Kurogi, Ying Hui, Yoichi Sakakibara, Masahito Suiko, Ming-Cheh Liu
The aim of the current study was to identify the human cytosolic sulfotransferases (SULTs) that are capable of sulfating clioquinol and iodoquinol, and to verify the presence of clioquinol/iodoquinol-sulfating activity in human organ homogenates. A systematic analysis revealed that six of the thirteen known human SULTs, SULT1A1 SULT1A2, SULTA3, SULT1B1, SULT1C4, and SULT1E1 showed considerable clioquinol/iodoquinol-sulfating activity. Kinetic parameters of the sulfation of clioquinol and iodoquinol by three SULTs, SULT1A1, SULT1A3, and SULT1C4, that showed the strongest clioquinol/iodoquinol-sulfating activity were determined...
July 19, 2016: Drug Metabolism Letters
Li Zhao, Pupu Zhang, Shiyang Long, Linlin Wang, Hanyong Jin, Weiwei Han, Pu Tian
Cytosolic sulfotransferases (SULTs) catalyze the transfer of a sulfonate group from the unique cofactor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to a large number of diverse substrates. In this work, tunnels that facilitate the transport of substrates in the enzyme were studied, with and without bound cofactor, using extensive molecular dynamics simulations. Residues making up tunnels, as well as residues forming bottlenecks to the tunnels, were identified. Conformation analysis of the active-site cap was also performed...
August 2016: Journal of Molecular Modeling
Marcin Odachowski, Amadeu Bonet, Stephanie Essafi, Philip Conti-Ramsden, Jeremy N Harvey, Daniele Leonori, Varinder K Aggarwal
The stereospecific cross-coupling of secondary boronic esters with sp(2) electrophiles (Suzuki-Miyaura reaction) is a long-standing problem in synthesis, but progress has been achieved in specific cases using palladium catalysis. However, related couplings with tertiary boronic esters are not currently achievable. To address this general problem, we have focused on an alternative method exploiting the reactivity of a boronate complex formed between an aryl lithium and a boronic ester. We reasoned that subsequent addition of an oxidant or an electrophile would remove an electron from the aromatic ring or react in a Friedel-Crafts-type manner, respectively, generating a cationic species, which would trigger 1,2-migration of the boron substituent, creating the new C-C bond...
August 3, 2016: Journal of the American Chemical Society
Thomas A Baillie, Deepak Dalvie, Ivonne M C M Rietjens, S Cyrus Khojasteh
Since 1972, Drug Metabolism Reviews has been recognized as one of the principal resources for researchers in pharmacological, pharmaceutical and toxicological fields to keep abreast of advances in drug metabolism science in academia and the pharmaceutical industry. With a distinguished list of authors and editors, the journal covers topics ranging from relatively mature fields, such as cytochrome P450 enzymes, to a variety of emerging fields. We hope to continue this tradition with the current compendium of mini-reviews that highlight novel biotransformation processes that were published during the past year...
May 2016: Drug Metabolism Reviews
Ting Wang, Ian Cook, Thomas S Leyh
The human cytosolic sulfotransferases (SULTs) comprise a 13-member enzyme family that regulates the activities of hundreds, perhaps thousands, of signaling small molecules via regiospecific transfer of the sulfuryl moiety (-SO3) from PAPS (3'-phosphoadenosine 5'-phosphosulfate) to the hydroxyls and amines of acceptors. Signaling molecules regulated by sulfonation include numerous steroid and thyroid hormones, epinephrine, serotonin, and dopamine. SULT1A1, a major phase II metabolism SULT isoform, is found at a high concentration in liver and has recently been show to harbor two allosteric binding sites, each of which binds a separate and complex class of compounds: the catechins (naturally occurring polyphenols) and nonsteroidal anti-inflammatory drugs...
July 26, 2016: Biochemistry
Hiroshi Honda, Kazuyuki Minegawa, Yurika Fujita, Noriko Yamaguchi, Yoshihiro Oguma, Hansruedi Glatt, Naohiro Nishiyama, Toshio Kasamatsu
INTRODUCTION: Several alkenylbenzenes, including methyleugenol (ME), are present in a wide range of botanicals and exhibit carcinogenic and mutagenic properties. Negative results are generally obtained for alkenylbenzenes in standard in vitro genotoxicity tests, including the Ames test. A lack of mutagenicity observed in such tests is thought to result from impaired metabolic activation of alkenylbenzenes via hydroxylation, with subsequent sulfoconjugation to its ultimate mutagenic or carcinogenic form...
2016: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
Zachary E Tibbs, Charles N Falany
Cytosolic sulfotransferases (SULTs) biotransform small molecules to polar sulfate esters as a means to alter their activities within the body. Understanding the molecular mechanism by which the SULTs perform their function is important for optimizing future therapeutic applications. Recent evidence suggests each SULT isoform acts by a half-site reaction (HSR) mechanism, in which a single SULT dimer subunit is active at any given time. HSR requires communication through the highly conserved KxxxTVxxxE dimerization motif...
September 1, 2016: Biochemical Pharmacology
Rômi S Piazza, Rafael Trevisan, Fabrício Flores-Nunes, Guilherme Toledo-Silva, Nestor Wendt, Jacó J Mattos, Daína Lima, Satie Taniguchi, Silvio Tarou Sasaki, Álvaro C P Mello, Flávia L Zacchi, Miguel A S Serrano, Carlos H A M Gomes, Márcia C Bícego, Eduardo A de Almeida, Afonso C D Bainy
Understanding the mechanism of phenanthrene (PHE) biotransformation and related cellular responses in bivalves can be an important tool to elucidate the risks of polycyclic aromatic hydrocarbons (PAHs) to aquatic organisms. In the present study it was analyzed the transcriptional levels of 13 biotransformation genes related to cytochrome P450 (CYP), glutathione S-transferase (GST), sulfotransferase (SULT), flavin-containing monooxygenase and fatty acid-binding proteins by qPCR in gill of scallops Nodipecten nodosus exposed for 24 or 96h to 50 or 200μgL(-1) PHE (equivalent to 0...
August 2016: Aquatic Toxicology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"