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https://www.readbyqxmd.com/read/28971357/alternative-splicing-expanding-diversity-in-major-abc-and-slc-drug-transporters
#1
Ji Eun Park, Gongmi Ryoo, Wooin Lee
Alternative splicing is an important mechanism of genetic regulation enhancing diversity and complexity of the transcriptome and proteome from the finite number of genes. Many reported cases demonstrate that alternative splicing events can lead to changes in the expression/function of proteins during disease development and progression. For pharmacogenes that can influence drug disposition and response, the role of alternative splicing has begun to receive increasing attention as an under-explored source of variable drug response...
October 2, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28878041/characteristics-of-29-novel-atypical-solute-carriers-of-major-facilitator-superfamily-type-evolutionary-conservation-predicted-structure-and-neuronal-co-expression
#2
Emelie Perland, Sonchita Bagchi, Axel Klaesson, Robert Fredriksson
Solute carriers (SLCs) are vital as they are responsible for a major part of the molecular transport over lipid bilayers. At present, there are 430 identified SLCs, of which 28 are called atypical SLCs of major facilitator superfamily (MFS) type. These are MFSD1, 2A, 2B, 3, 4A, 4B, 5, 6, 6 L, 7, 8, 9, 10, 11, 12, 13A, 14A and 14B; SV2A, SV2B and SV2C; SVOP and SVOPL; SPNS1, SPNS2 and SPNS3; and UNC93A and UNC93B1. We studied their fundamental properties, and we also included CLN3, an atypical SLC not yet belonging to any protein family (Pfam) clan, because its involvement in the same neuronal degenerative disorders as MFSD8...
September 2017: Open Biology
https://www.readbyqxmd.com/read/28819401/identification-and-validation-of-soluble-carrier-family-expression-signature-for-predicting-poor-outcome-of-renal-cell-carcinoma
#3
Wan Fangning, Ma Chunguang, Zhang Hailiang, Shi Guohai, Zhu Yao, Dai Bo, Shen Yijun, Zhu Yiping, Ye Dingwei
The soluble carrier (SLC) family plays an important role in cell metabolism. The purpose of the current study was to screen SLCs as potential prognostic factors in clear cell renal cell carcinoma (ccRCC). A total of 509 patients with ccRCC from The Cancer Genome Atlas (TCGA) cohort were enrolled in this study. The expression profile of SLCs was obtained from the TCGA RNAseq database. Metadata of the TCGA cohort, including age, sex, TNM stage, tumor grade, American Joint Committee on Cancer stage, laterality, and overall survival, were collected...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28768834/placentome-nutrient-transporters-and-mammalian-target-of-rapamycin-signaling-proteins-are-altered-by-the-methionine-supply-during-late-gestation-in-dairy-cows-and-are-associated-with-newborn-birth-weight
#4
Fernanda Batistel, Abdulrahman Sm Alharthi, Ling Wang, Claudia Parys, Yuan-Xiang Pan, Felipe C Cardoso, Juan J Loor
Background: To our knowledge, most research demonstrating a link between maternal nutrition and both fetal growth and offspring development after birth has been performed with nonruminants. Whether such relationships exist in large ruminants is largely unknown.Objective: We aimed to investigate whether increasing the methionine supply during late pregnancy would alter uteroplacental tissue nutrient transporters and mammalian target of rapamycin (mTOR) and their relation with newborn body weight.Methods: Multiparous Holstein cows were used in a randomized complete block design experiment...
September 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28756021/association-of-clinical-severity-of-cystic-fibrosis-with-variants-in-the-slc-gene-family-slc6a14-slc26a9-slc11a1-and-slc9a3
#5
Stéphanie Villa-Nova Pereira, José Dirceu Ribeiro, Carmen Sílvia Bertuzzo, Fernando Augusto Lima Marson
INTRODUCTION: Cystic fibrosis (CF) manifests with clinical and histopathological variability depending on environmental and genetic factors. Moreover, the genes encoding ion channels[rs3788766(SLC6A14), rs7512462(SLC26A9), rs17235416(SLC11A1) and rs17563161(SLC9A3)] have been insufficiently studied as modifier genes. Then, our objective was associate the variants in the genes of SLC family with 43 CF severity markers. METHODS: The variants were identified by real-time-PCR in 188 CF patients considering the CFTR genotype...
September 20, 2017: Gene
https://www.readbyqxmd.com/read/28753996/boron-tolerance-in-aspergillus-nidulans-is-sustained-by-the-slta-pathway-through-the-slc-family-transporters-sbta-and-sbtb
#6
María Villarino, Oier Etxebeste, Gorka Mendizabal, Aitor Garzia, Unai Ugalde, Eduardo A Espeso
Microbial cells interact with the environment by adapting to external changes. Signal transduction pathways participate in both sensing and responding in the form of modification of gene expression patterns, enabling cell survival. The filamentous fungal-specific SltA pathway regulates tolerance to alkalinity, elevated cation concentrations and, as shown in this work, also stress conditions induced by borates. Growth of sltA(-) mutants is inhibited by increasing millimolar concentrations of boric acid or borax (sodium tetraborate)...
July 21, 2017: Genes
https://www.readbyqxmd.com/read/28717013/mechanisms-of-carbon-dioxide-acquisition-and-co2-sensing-in-marine-diatoms-a-gateway-to-carbon-metabolism
#7
REVIEW
Yusuke Matsuda, Brian M Hopkinson, Kensuke Nakajima, Christopher L Dupont, Yoshinori Tsuji
Diatoms are one of the most successful marine eukaryotic algal groups, responsible for up to 20% of the annual global CO2 fixation. The evolution of a CO2-concentrating mechanism (CCM) allowed diatoms to overcome a number of serious constraints on photosynthesis in the marine environment, particularly low [CO2]aq in seawater relative to concentrations required by the CO2 fixing enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO), which is partly due to the slow diffusion rate of CO2 in water and a limited CO2 formation rate from [Formula: see text] in seawater...
September 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28698977/pharmacogenetics-and-pharmacogenomics-of-targeted-therapeutics-in-chronic-myeloid-leukemia
#8
REVIEW
Aritro Nath, Jacqueline Wang, R Stephanie Huang
The advent of targeted therapeutics has greatly improved outcomes of chronic myeloid leukemia (CML) patients. Despite increased efficacy and better clinical responses over cytotoxic chemotherapies, many patients receiving targeted drugs exhibit a poor initial response, develop drug resistance, or undergo relapse after initial success. This inter-individual variation in response has heightened the interest in studying pharmacogenetics and pharmacogenomics (PGx) of cancer drugs. In this review, we discuss the influence of various germline and somatic factors on targeted drug response in CML...
July 11, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28664465/slc-and-abc-transporters-expression-localization-and-species-differences-at-the-blood-brain-and-the-blood-cerebrospinal-fluid-barriers
#9
Marilyn E Morris, Vivian Rodriguez-Cruz, Melanie A Felmlee
The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) separate the brain and cerebrospinal fluid (CSF) from the systemic circulation and represent a barrier to the uptake of both endogenous compounds and xenobiotics into the brain. For compounds whose passive diffusion is limited due to their ionization or hydrophilicity, membrane transporters can facilitate their uptake across the BBB or BCSFB. Members of the solute carrier (SLC) and ATP-binding case (ABC) families are present on these barriers...
June 29, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28638886/mechanisms-of-coix-seed-compositions-in-the-treatment-of-spleen-deficiency-and-wet-dampness-zheng
#10
Xiaochun Han, Xuming Ji, Haijun Zhao, Yanan Zhang, Guowei Liu, Yanfang Wang, Wenxiao Zhao, Shijun Wang
BACKGROUND: Coix seed has the functions of fortifying the spleen and inhibiting the dampness. However, it remains unclear which Coix seed compositions is responsible for these functions. Previous investigations have revealed that the main compositions of Coix seed are proteins, polysaccharides, oils and starches. The objectives of this study are to explore which is the most effective compositions in fortifying the spleen and examine how Coix seed works in regulating the water transport on the spleen deficiency and wet dampness (SDWD) rat model...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28633304/molecular-aspects-of-the-biophysical-co2-concentrating-mechanism-and-its-regulation-in-marine-diatoms
#11
Yoshinori Tsuji, Kensuke Nakajima, Yusuke Matsuda
Diatoms operate a CO2-concentrating mechanism (CCM) that drives upwards of 20% of annual global primary production. Recent progress in CCM research in the marine pennate diatom Phaeodactylum tricornutum revealed that this diatom directly takes up HCO3- from seawater through low-CO2-inducible plasma membrane HCO3- transporters, which belong to the solute carrier (SLC) 4 family. Apart from this, studies of carbonic anhydrases (CAs) in diatoms have revealed considerable diversity in classes and localization among species...
June 1, 2017: Journal of Experimental Botany
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
#12
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
#13
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...
July 2017: AAPS Journal
https://www.readbyqxmd.com/read/28363126/interaction-between-the-zebrafish-danio-rerio-organic-cation-transporter-1-oct1-and-endo-and-xenobiotics
#14
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/28343125/structural-modeling-of-human-organic-cation-transporters
#15
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
#16
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
https://www.readbyqxmd.com/read/28257821/tight-junction-protein-zo-1-controls-organic-cation-carnitine-transporter-octn2-slc22a5-in-a-protein-kinase-c-dependent-way
#17
Dominika Jurkiewicz, Katarzyna Michalec, Krzysztof Skowronek, Katarzyna A Nałęcz
OCTN2 (SLC22A5) is an organic cation/carnitine transporter belonging to the solute carrier transporters (SLC) family. OCTN2 is ubiquitously expressed and its presence was shown in various brain cells, including the endothelial cells forming blood-brain barrier, where it was mainly detected at abluminal membrane and in proximity of tight junctions (TJ). Since OCTN2 contains a PDZ-binding domain, the present study was focused on a possible role of transporter interaction with a TJ-associated protein ZO-1, containing PDZ domains and detected in rat Octn2 proteome...
May 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28214518/potentiating-slc-transporter-activity-emerging-drug-discovery-opportunities
#18
REVIEW
Marie-Laure Rives, Jonathan A Javitch, Alan D Wickenden
Maintaining the integrity of cellular membranes is critical to protecting metabolic activities and genetic information from the environment. Regulation of transport across membranes of essential chemicals, including water, nutrients, hormones and many drugs, is therefore key to cellular homeostasis and physiological processes. The two main transporter superfamilies are ATP-binding cassette (ABC) transporters that primarily function as efflux transporters, and the solute carrier (SLC) transporters. SLC transporters encompass 52 gene families with almost 400 different human transporter genes...
July 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28178198/zinc-transporter-3-znt3-in-the-enteric-nervous-system-of-the-porcine-ileum-in-physiological-conditions-and-during-experimental-inflammation
#19
Sławomir Gonkowski, Maciej Rowniak, Joanna Wojtkiewicz
Zinc transporter 3 (ZnT3) is a member of the solute-linked carrier 30 (SLC 30) zinc transporter family. It is closely linked to the nervous system, where it takes part in the transport of zinc ions from the cytoplasm to the synaptic vesicles. ZnT3 has also been observed in the enteric nervous system (ENS), but its reactions in response to pathological factors remain unknown. This study, based on the triple immunofluorescence technique, describes changes in ZnT3-like immunoreactive (ZnT3-LI) enteric neurons in the porcine ileum, caused by chemically-induced inflammation...
February 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28176814/eunag-a-new-ligand-inducible-fluorescent-reporter-to-detect-drug-transporter-activity-in-live-cells
#20
Johannes T-H Yeh, Kwangho Nam, Joshua T-H Yeh, Norbert Perrimon
The absorption, distribution, metabolism and excretion (ADME) of metabolites and toxic organic solutes are orchestrated by the ATP-binding cassette (ABC) transporters and the organic solute carrier family (SLC) proteins. A large number of ABC and SLC transpoters exist; however, only a small number have been well characterized. To facilitate the analysis of these transporters, which is important for drug safety and physiological studies, we developed a sensitive genetically encoded bilirubin (BR)-inducible fluorescence sensor (eUnaG) to detect transporter-coupled influx/efflux of organic compounds...
February 8, 2017: Scientific Reports
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