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https://www.readbyqxmd.com/read/28481715/efflux-proteins-at-the-blood-brain-barrier-review-and-bioinformatics-analysis
#1
Massoud Saidijam, Fatemeh Karimi Dermani, Sareh Sohrabi, Simon G Patching
1. Efflux proteins at the blood-brain barrier provide a mechanism for export of waste products of normal metabolism from the brain and help to maintain brain homeostasis. They also prevent entry into the brain of a wide range of potentially harmful compounds such as drugs and xenobiotics. 2. Conversely, efflux proteins also hinder delivery of therapeutic drugs to the brain and central nervous system used to treat brain tumours and neurological disorders. For bypassing efflux proteins, a comprehensive understanding of their structures, functions and molecular mechanisms is necessary, along with new strategies and technologies for delivery of drugs across the blood-brain barrier...
May 8, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28474563/opioids-and-the-blood-brain-barrier-a-dynamic-interaction-with-consequences-on-drug-disposition-in-brain
#2
Catarina Chaves, Fernando Remião, Salvatore Cisterninoa, Xavier Declèves
Opioids are widely used in pain management whose effects are due to binding to classical opioid receptors and/or Toll-like receptors (TLR) present at the central nervous system (CNS). At the blood-brain barrier (BBB), several influx and/or efflux transporters are expressed, such as the ATP-binding cassette (ABC) P-glycoprotein (P-gp, ABCB1), Breast Cancer Resistance Protein (BCRP, ABCG2) and multidrug resistance-associated proteins (MRP, ABCC) transporters, and solute carrier transporters (SLC), and are responsible for the transport of many xenobiotics from the brain into the bloodstream or vice versa...
May 3, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28470523/assays-for-analyzing-the-role-of-transport-proteins-in-the-uptake-and-the-vectorial-transport-of-substances-affecting-cell-viability
#3
Emir Taghikhani, Martin F Fromm, Jörg König
Endogenous compounds, drugs, or other xenobiotics may affect cell viability. A prerequisite for intracellular cell damage is the uptake of such substances across the plasma membrane into cells. Furthermore, the subsequent transporter-mediated export out of cells may influence cell viability. Therefore, transport proteins mediating the uptake (uptake transporter) or export (export pumps) of substances in and out of cells are important determinants of cell viability. Uptake transporters mostly belong to the superfamily of solute carriers (SLC transporters), whereas export pumps are members of the ABC-transporter superfamily (ATP-binding cassette)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28456731/different-involvement-of-oat-in-renal-disposition-of-oral-anticoagulants-rivaroxaban-dabigatran-and-apixaban
#4
Yuri Tsuruya, Takeo Nakanishi, Hisakazu Komori, Xinying Wang, Naoki Ishiguro, Tomoko Kito, Kouji Ikukawa, Wataru Kishimoto, Sumito Ito, Olaf Schaefer, Thomas Ebner, Norio Yamamura, Hiroyuki Kusuhara, Ikumi Tamai
This study aimed to investigate the interactions of three anti-coagulants, rivaroxaban, apixaban, and dabigatran, with five human SLC transporters, hOAT1, hOAT3, hOCT2, hOATP1B1, and hOATP1B3. Apixaban inhibited hOAT3, hOATP1B1, and hOATP1B3, and rivaroxaban inhibited hOAT3 and hOATP1B3, with IC50 values of > 20 and >5 μM, respectively. The effect of dabigatran was negligible or very weak, so significant drug interactions at therapeutic doses are unlikely. Specific uptake of rivaroxaban was observed only in human and mouse OAT3-expressing cells...
April 26, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28454689/identification-of-appropriate-reference-genes-for-qpcr-analyses-of-placental-expression-of-slc7a3-and-induction-of-slc5a1-in-porcine-endometrium
#5
Chelsie B Steinhauser, Theodore T Wing, Haijun Gao, Xilong Li, Robert C Burghardt, Guoyao Wu, Fuller W Bazer, Greg A Johnson
INTRODUCTION: Endometria and placentae undergo developmental changes that affect the stability of genes used as references for normalization of qPCR data. We identified genes that are stable within the porcine endometrium and placenta throughout pregnancy, and elucidated the temporal/spatial mRNA localization of the glucose and arginine transporters, solute carrier family (SLC) 5A1 and SLC7A3, respectively. MATERIALS AND METHODS: qPCR was performed for 10 genes within porcine endometria from Days 5, 11, and 15 of the estrous cycle and 11, 15, 25, 40, 60, and 85 of pregnancy; and chorioallantois from Days 30, 35, 45, 50, 60, and 85...
April 2017: Placenta
https://www.readbyqxmd.com/read/28447295/functional-expression-of-p-glycoprotein-and-organic-anion-transporting-polypeptides-at-the-blood-brain-barrier-understanding-transport-mechanisms-for-improved-cns-drug-delivery
#6
Wazir Abdullahi, Thomas P Davis, Patrick T Ronaldson
Drug delivery to the central nervous system (CNS) is greatly limited by the blood-brain barrier (BBB). Physical and biochemical properties of the BBB have rendered treatment of CNS diseases, including those with a hypoxia/reoxygenation (H/R) component, extremely difficult. Targeting endogenous BBB transporters from the ATP-binding cassette (ABC) superfamily (i.e., P-glycoprotein (P-gp)) or from the solute carrier (SLC) family (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents)) has been suggested as a strategy that can improve delivery of drugs to the brain...
April 26, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28432346/functionally-interchangeable-cis-acting-rna-elements-in-both-genome-segments-of-a-picorna-like-plant-virus
#7
Jiangbo Guo, Junping Han, Junyan Lin, John Finer, Anne Dorrance, Feng Qu
Cis-acting RNA structures in the genomes of RNA viruses play critical roles in viral infection, yet their importance in the bipartite genomes of the picorna-like, plant-infecting comoviruses has not been carefully investigated. We previously characterized SLC, a stem-loop structure in the 5' untranslated region (UTR) of the bean pod mottle comovirus (BPMV) RNA2, and found it to be essential for RNA2 accumulation in infected cells. Here we report the identification of SL1, a similar cis-acting element in the other BPMV genome segment - RNA1...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28425971/%C3%AF-%C3%A2-cells-feature-de-ubiquitination-of-slc-transporters-and-increased-levels-and-fluxes-of-amino-acids
#8
André Bordinassi Medina, Marcin Banaszczak, Yang Ni, Ina Aretz, David Meierhofer
Solute carrier (SLC) transporters are a diverse group of membrane transporter proteins that regulate the cellular flux and distribution of endogenous and xenobiotic compounds. Post-translational modifications (PTMs), such as ubiquitination, have recently emerged as one of the major regulatory mechanisms in protein function and localization. Previously, we showed that SLC amino acid transporters were on average 6-fold de-ubiquitinated and increased amino acid levels were detected in ρ⁰ cells (lacking mitochondrial DNA, mtDNA) compared to parental cells...
April 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28420426/genotypes-of-slc22a4-and-slc22a5-regulatory-loci-are-predictive-of-the-response-of-chronic-myeloid-leukemia-patients-to-imatinib-treatment
#9
Monika Jaruskova, Nikola Curik, Rajna Hercog, Vaclava Polivkova, Eliska Motlova, Vladimir Benes, Hana Klamova, Pavla Pecherkova, Petra Belohlavkova, Filip Vrbacky, Katerina Machova Polakova
BACKGROUND: Through high-throughput next-generation sequencing of promoters of solute carrier and ATP-binding cassette genes, which encode drug transporters, we aimed to identify SNPs associated with the response to imatinib administered for first-line treatment of patients with chronic myeloid leukemia. METHODS: In silico analysis using publicly available databases was done to select the SLC and ABC genes and their promoters for the next-generation sequencing. SNPs associated with the imatinib response were identified using Fisher's exact probability tests and subjected to the linkage disequilibrium analyses with regulatory loci of concerned genes...
April 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28408210/the-organic-anion-transporting-peptide-2b1-is-localized-in-the-basolateral-membrane-of-the-human-jejunum-and-caco-2-monolayers
#10
Markus Keiser, Lars Kaltheuner, Charlotte Wildberg, Janett Müller, Markus Grube, Lars Ivo Partecke, Claus-Dieter Heidecke, Stefan Oswald
The organic anion-transporting polypeptide (OATP) 2B1 which is ubiquitously expressed in the human body is assumed to play an important role in the cellular uptake of many drugs. Although the expression and function of this solute carrier transporter is well characterized in the human liver and other tissues, little is known about its localization and functional relevance in the intestine. Thus, it was the aim of this study to investigate its localization and function in the human jejunum and in the frequently used intestinal Caco-2 cell line...
April 10, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28398591/evolutionarily-distinct-strategies-for-the-acquisition-of-inorganic-carbon-from-seawater-in-marine-diatoms
#11
Yoshinori Tsuji, Anggara Mahardika, Yusuke Matsuda
The acquisition of dissolved inorganic carbon (DIC) in CO2-limited seawater is a central issue to understand in marine primary production. We previously demonstrated the occurrence of direct HCO3- uptake by solute carrier (SLC) 4 transporters in a diatom, a major marine primary producer. Homologs of SLC are found in both centric and pennate marine diatoms, suggesting that SLC transporters are generally conserved. Here, the generality of SLC-mediated DIC uptake in diatoms was examined using an SLC inhibitor, diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS), and an inhibitor of external carbonic anhydrase, acetazolamide...
April 8, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28375174/protein-kinases-c-mediated-regulations-of-drug-transporter-activity-localization-and-expression
#12
REVIEW
Abdullah Mayati, Amélie Moreau, Marc Le Vée, Bruno Stieger, Claire Denizot, Yannick Parmentier, Olivier Fardel
Drug transporters are now recognized as major actors in pharmacokinetics, involved notably in drug-drug interactions and drug adverse effects. Factors that govern their activity, localization and expression are therefore important to consider. In the present review, the implications of protein kinases C (PKCs) in transporter regulations are summarized and discussed. Both solute carrier (SLC) and ATP-binding cassette (ABC) drug transporters can be regulated by PKCs-related signaling pathways. PKCs thus target activity, membrane localization and/or expression level of major influx and efflux drug transporters, in various normal and pathological types of cells and tissues, often in a PKC isoform-specific manner...
April 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28373627/effects-of-transplanted-human-cord-blood-mononuclear-cells-on-pulmonary-hypertension-in-immunodeficient-mice-and-their-distribution
#13
Mikio Sugano, Homare Yoshida, Hirotsugu Kurobe, Hiroki Arase, Hajime Kinoshita, Takashi Kitaichi, Noriko Sugasawa, Soichiro Nakayama, Kazuhisa Maeda, Minoru Irahara, Tetsuya Kitagawa
OBJECTIVES: To investigate the effects of human umbilical cord blood-derived mononuclear cell (hUCB-MNC) transplantation on pulmonary hypertension (PH) induced by monocrotaline (MCT) in immunodeficient mice and their distribution. METHODS: MCT was administered to BALB/c Slc-nu/nu mice, and PH was induced in mice 4 weeks later. Fresh hUCB-MNCs harvested from a human donor after her delivery were injected intravenously into those PH mice. The medial thickness of pulmonary arterioles, ratio of right ventricular to septum plus left ventricular weight (RV/S+LV), and ratio of acceleration time to ejection time of pulmonary blood flow waveform (AT/ET) were determined 4 weeks after hUCB-MNC transplantation...
2017: Journal of Medical Investigation: JMI
https://www.readbyqxmd.com/read/28363153/structure-activity-study-of-carbonic-anhydrase-ix-selective-inhibition-with-ureido-substituted-benzenesulfonamides
#14
Mam Y Mboge, Brian P Mahon, Nicole Lamas, Lillien Socorro, Fabrizio Carta, Claudiu T Supuran, Susan C Frost, Robert McKenna
Ureido-substituted benzenesulfonamides (USBs) show great promise as selective and potent inhibitors for human carbonic anhydrase hCA IX and XII, with one such compound (SLC-0111/U-F) currently in clinical trials (clinical trials.gov, NCT02215850). In this study, the crystal structures of both hCA II (off-target) and an hCA IX-mimic (target) in complex with selected USBs (U-CH3, U-F, and U-NO2), at resolutions of 1.9 Å or better, are presented, and demonstrate differences in the binding modes within the two isoforms...
March 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28363126/interaction-between-the-zebrafish-danio-rerio-organic-cation-transporter-1-oct1-and-endo-and-xenobiotics
#15
Ivan Mihaljević, Marta Popović, Roko Žaja, Nikola Maraković, Goran Šinko, Tvrtko Smital
Organic cation transporters (OCTs) serve as uptake transporters of numerous endo- and xenobiotics. They have been in the focus of medical toxicological research for more than a decade due to their key role in absorption, distribution, metabolism and excretion due to their expression on basolateral membranes of various barrier tissues. OCTs belong to the SLC22A family within the SLC (Solute carrier) protein superfamily, with three co-orthologs identified in humans (OCT1, 2 and 3), and two Oct orthologs in zebrafish (Oct1 and Oct2)...
June 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28350329/harnessing-solute-carrier-transporters-for-precision-oncology
#16
REVIEW
Michael D Nyquist, Bhagwat Prasad, Elahe A Mostaghel
Solute Carrier (SLC) transporters are a large superfamily of transmembrane carriers involved in the regulated transport of metabolites, nutrients, ions and drugs across cellular membranes. A subset of these solute carriers play a significant role in the cellular uptake of many cancer therapeutics, ranging from chemotherapeutics such as antimetabolites, topoisomerase inhibitors, platinum-based drugs and taxanes to targeted therapies such as tyrosine kinase inhibitors. SLC transporters are co-expressed in groups and patterns across normal tissues, suggesting they may comprise a coordinated regulatory circuit serving to mediate normal tissue functions...
March 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28347633/synthesis-and-carbonic-anhydrase-inhibition-of-a-series-of-slc-0111-analogs
#17
Fabrizio Carta, Daniela Vullo, Sameh M Osman, Zeid AlOthman, Claudiu T Supuran
SLC-0111 is a sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor (CAI) in Phase I/II clinical trials for the treatment of advanced hypoxic tumors complicated with metastases. Its antitumor effects are due to inhibition of the enzymatic activity of CA IX, an isoform predominantly found in tumors/metastases, but it also reduces the cancer stem cells population. Here we report the synthesis of analogs of SLC-0111, both of the sulfanilamide and metanilamide series, which possess diverse substitution patterns at the terminal ureido-phenyl moiety, thus including one or more halogens, trifluoromethyl, perchloro-/perfluorophenyl groups instead of the 4-fluorophenyl present in SLC-0111...
March 18, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28343884/short-term-desensitization-of-fast-escape-behavior-associated-with-suppression-of-mauthner-cell-activity-in-larval-zebrafish
#18
Megumi Takahashi, Maya Inoue, Masashi Tanimoto, Tsunehiko Kohashi, Yoichi Oda
Escape is among the simplest animal behaviors employed to study the neural mechanisms underlying learning. Teleost fishes exhibit behavioral learning of fast escape initiated with a C-shaped body bend (C-start). C-starts are subdivided into short-latency (SLC) and long-latency (LLC) types in larval zebrafish. Whether these two can be separately modified, and the neural correlates of this modification, however, remains undetermined. We thus performed Ca(2+) imaging of Mauthner (M-) cells, a pair of giant hindbrain neurons constituting a core element of SLC circuit, during behavioral learning in larval zebrafish...
March 23, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28343125/structural-modeling-of-human-organic-cation-transporters
#19
Tikam Chand Dakal, Rajender Kumar, Dindial Ramotar
Human organic cation transporters (hOCTs) belong to solute carriers (SLC) 22 family of membrane proteins that play a central role in transportation of chemotherapeutic drugs for several clinical and pathological conditions, including cancer and diabetes. These transporters mediate drug transport; however, the precise mechanism of drug-binding and transport by them is not fully uncovered yet, partly due to unavailability of any crystal structure record. In this work, we performed a multi-phasic approach to compute the 3D structural models of seven human organic cation transporters (hOCTs) starting from primary protein sequence...
March 18, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28339967/placental-transporter-localization-and-expression-in-the-human-the-importance-of-species-sex-and-gestational-age-differences%C3%A2
#20
Natasha Walker, Panagiotis Filis, Ugo Soffientini, Michelle Bellingham, Peter J O'Shaughnessy, Paul A Fowler
The placenta is a critical organ during pregnancy, essential for the provision of an optimal intrauterine environment, with fetal survival, growth, and development relying on correct placental function. It must allow nutritional compounds and relevant hormones to pass into the fetal bloodstream and metabolic waste products to be cleared. It also acts as a semipermeable barrier to potentially harmful chemicals, both endogenous and exogenous. Transporter proteins allow for bidirectional transport and are found in the syncytiotrophoblast of the placenta and endothelium of fetal capillaries...
April 1, 2017: Biology of Reproduction
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