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https://www.readbyqxmd.com/read/28363126/interaction-between-the-zebrafish-danio-rerio-organic-cation-transporter-1-oct1-and-endo-and-xenobiotics
#1
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)...
March 18, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28343125/structural-modeling-of-human-organic-cation-transporters
#2
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-differences1
#3
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 semi-permeable 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...
March 7, 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
#4
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
#5
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...
February 15, 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
#6
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
#7
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
https://www.readbyqxmd.com/read/28025785/significance-of-oct1-expression-in-acute-myeloid-leukemia
#8
Ewa Stefanko, Justyna Rybka, Bożena Jaźwiec, Olga Haus, Sylwia Stąpor, Kazimierz Kuliczkowski, Tomasz Wróbel
Organic cation transporter 1 (OCT1) is one of the membrane proteins in the large solute carrier (SLC) family. It participates in the transport of organic cations, i.e. nutrients, neurotransmitters, metabolites or drugs in an electrogenic manner and translocate various cationic cytostatics. Knowledge concerning the expression of drug transporters in tumor cells may help to develop cytotoxic agents that are targeted to specific tumors. OCT1 expression and its relationship to the proliferation of cancer cells, development of metastases and resistance to chemotherapy has been observed in solid tumors...
December 26, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/27981419/the-novel-membrane-bound-proteins-mfsd1-and-mfsd3-are-putative-slc-transporters-affected-by-altered-nutrient-intake
#9
Emelie Perland, Sofie V Hellsten, Emilia Lekholm, Mikaela M Eriksson, Vasiliki Arapi, Robert Fredriksson
Membrane-bound solute carriers (SLCs) are essential as they maintain several physiological functions, such as nutrient uptake, ion transport and waste removal. The SLC family comprise about 400 transporters, and we have identified two new putative family members, major facilitator superfamily domain containing 1 (MFSD1) and 3 (MFSD3). They cluster phylogenetically with SLCs of MFS type, and both proteins are conserved in chordates, while MFSD1 is also found in fruit fly. Based on homology modelling, we predict 12 transmembrane regions, a common feature for MFS transporters...
February 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27872146/organic-anion-transporter-2-oat2-an-enigmatic-human-solute-carrier
#10
Hong Shen, Yurong Lai, A David Rodrigues
As a member of the solute carrier 22A (SLC22A) family, OAT2 (SLC22A7) is emerging as an important drug transporter because of its expression in both the liver and kidney, two major eliminating organs, and its ability to transport not only a wide variety of xenobiotics, but also numerous physiologically important endogenous compounds, like creatinine and guanosine 3,5-cyclic monophosphate (cGMP). However, OAT2 has received relatively little attention when compared to other OATs and solute carriers (SLCs) like organic cation transporters, sodium-dependent taurocholate co-transporting polypeptide, multidrug and toxin extrusion proteins, and organic anion-transporting polypeptides...
November 21, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27812757/counter-flow-suggests-transport-of-dantrolene-and-5-oh-dantrolene-by-the-organic-anion-transporters-2-oat2-and-3-oat3
#11
Birgitta C Burckhardt, Maja Henjakovic, Yohannes Hagos, Gerhard Burckhardt
Dantrolene is the only available drug for the treatment of malignant hyperthermia, a life-threatening inborn sensitivity of the ryanodine receptor (RyR1) in skeletal muscles to volatile anesthetics. Dantrolene is metabolized in the liver to 5-OH dantrolene. Both compounds are zwitterions or net negatively charged. Here, we investigated interactions of dantrolene and 5-OH dantrolene with solute carrier (SLC) family members occurring in skeletal muscle cells, hepatocytes, and renal proximal tubule cells. SLC22A8 (organic anion transporter 3, OAT3) was very sensitive to both compounds exhibiting IC50 values of 0...
November 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27796869/zinc-transporter-3-znt3-as-an-active-substance-in-the-enteric-nervous-system-of-the-porcine-esophagus
#12
Joanna Wojtkiewicz, Krystyna Makowska, Ewa Bejer-Olenska, Sławomir Gonkowski
Zinc transporter 3 (ZnT3), a member of the SLC 30 zinc transporter family, is involved in the transport of zinc ions from the cytoplasm into synaptic vesicles or intracellular organelles. The aim of the present study was to investigate for the first time the percentage of ZnT3-like immunoreactive (ZnT3-LI) neurons in the enteric nervous system (ENS) of the porcine esophagus and denotation of their neurochemical coding. Routine double- and triple-immunofluorescence labeling of cervical, thoracic, and abdominal fragments of esophagus for ZnT3 with protein gene product (PGP 9...
March 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27672436/slc-transporters-structure-function-and-drug-discovery
#13
Claire Colas, Peter Man-Un Ung, Avner Schlessinger
The human Solute Carrier (SLC) transporters are important targets for drug development. Structure-based drug discovery for SLC transporters requires the description of their structure, dynamics, and mechanism of interaction with small molecule ligands and ions. The recent determination of atomic structures of human SLC transporters and their homologs, combined with improved computational power and prediction methods have led to an increased applicability of structure-based drug design methods for human SLC members...
June 1, 2016: MedChemComm
https://www.readbyqxmd.com/read/27601653/structure-of-bor1-supports-an-elevator-transport-mechanism-for-slc4-anion-exchangers
#14
Bryan H Thurtle-Schmidt, Robert M Stroud
Boron is essential for plant growth because of its incorporation into plant cell walls; however, in excess it is toxic to plants. Boron transport and homeostasis in plants is regulated in part by the borate efflux transporter Bor1, a member of the solute carrier (SLC) 4 transporter family with homology to the human bicarbonate transporter Band 3. Here, we present the 4.1-Å resolution crystal structure of Arabidopsis thaliana Bor1. The structure displays a dimeric architecture in which dimerization is mediated by centralized Gate domains...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27519738/phylogenetic-syntenic-and-tissue-expression-analysis-of-slc22-genes-in-zebrafish-danio-rerio
#15
Ivan Mihaljevic, Marta Popovic, Roko Zaja, Tvrtko Smital
BACKGROUND: SLC22 protein family is a member of the SLC (Solute carriers) superfamily of polyspecific membrane transporters responsible for uptake of a wide range of organic anions and cations, including numerous endo- and xenobiotics. Due to the lack of knowledge on zebrafish Slc22 family, we performed initial characterization of these transporters using a detailed phylogenetic and conserved synteny analysis followed by the tissue specific expression profiling of slc22 transcripts. RESULTS: We identified 20 zebrafish slc22 genes which are organized in the same functional subgroups as human SLC22 members...
August 12, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27503090/solute-carriers-in-the-blood-brain-barier-safety-in-abundance
#16
Katarzyna A Nałęcz
Blood-brain barrier formed by brain capillary endothelial cells, being in contact with astrocytes endfeet and pericytes, separates extracellular fluid from plasma. Supply of necessary nutrients and removal of certain metabolites takes place due to the activity of transporting proteins from ABC (ATP binding cassette) and SLC (solute carrier) superfamilies. This review is focused on the SLC families involved in transport though the blood-brain barrier of energetic substrates (glucose, monocarboxylates, creatine), amino acids, neurotransmitters and their precursors, as well as organic ions...
March 2017: Neurochemical Research
https://www.readbyqxmd.com/read/27471394/decreased-expression-of-slc-39a14-is-associated-with-tumor-aggressiveness-and-biochemical-recurrence-of-human-prostate-cancer
#17
Xiao-Ming Xu, Cheng-Gong Wang, Yu-Di Zhu, Wei-Hua Chen, Si-Liang Shao, Fu-Neng Jiang, Qian-De Liao
OBJECTIVE: Solute carrier family 39, member 14 (SLC39A14), has been identified as a potential biomarker for various cancers. However, its roles in prostate cancer (PCa) are still unclear. The aim of this study was to investigate the clinical significance of SLC39A14 in patients with PCa and its functions in malignant phenotypes of PCa cells. PATIENTS AND METHODS: Subcellular localization and expression pattern of SLC39A14 protein were examined by immunohistochemistry...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27440044/an-organic-anion-transporter-1-oat1-centered-metabolic-network
#18
Henry C Liu, Neema Jamshidi, Yuchen Chen, Satish A Eraly, Sai Yee Cho, Vibha Bhatnagar, Wei Wu, Kevin T Bush, Ruben Abagyan, Bernhard O Palsson, Sanjay K Nigam
There has been a recent interest in the broader physiological importance of multispecific "drug" transporters of the SLC and ABC transporter families. Here, a novel multi-tiered systems biology approach was used to predict metabolites and signaling molecules potentially affected by the in vivo deletion of organic anion transporter 1 (Oat1, Slc22a6, originally NKT), a major kidney-expressed drug transporter. Validation of some predictions in wet-lab assays, together with re-evaluation of existing transport and knock-out metabolomics data, generated an experimentally validated, confidence ranked set of OAT1-interacting endogenous compounds enabling construction of an "OAT1-centered metabolic interaction network...
September 9, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27422508/metallothionein-and-zinc-transporter-expression-in-circulating-human-blood-cells-as-biomarkers-of-zinc-status-a-systematic-review
#19
REVIEW
Stephen R Hennigar, Alyssa M Kelley, James P McClung
Zinc is an essential nutrient for humans; however, a sensitive biomarker to assess zinc status has not been identified. The objective of this systematic review was to compile and assess studies that determined zinc transporter and/or metallothionein expression in various blood cell types and to determine their reliability and sensitivity to changes in dietary zinc. Sixteen studies were identified that determined the expression of zrt-, irt-like protein (ZIP) 1 [solute carrier family (SLC) 39A1], ZIP3 (SLC39A3), ZIP5 (SLC39A5), ZIP6 (SLC39A6), ZIP7 (SLC39A7), ZIP8 (SLC39A8), ZIP10 (SLC39A10), ZIP14 (SLC39A14), zinc transporter (ZnT)1 (SLC30A1), ZnT2 (SLC30A2), ZnT4 (SLC30A4), ZnT5 (SLC30A5), ZnT6 (SLC30A6), ZnT7 (SLC30A7), ZnT9 (SLC30A9), and/or metallothionein in various blood cells isolated from healthy adult men and women in response to zinc supplementation or depletion...
July 2016: Advances in Nutrition
https://www.readbyqxmd.com/read/27421837/an-integrative-in-silico-system-for-predicting-dysregulated-genes-in-the-human-epileptic-focus-application-to-slc-transporters
#20
Nasir Mirza, Olga Vasieva, Richard Appleton, Sasha Burn, Daniel Carr, Daniel Crooks, Daniel du Plessis, Roderick Duncan, Jibril Osman Farah, Vivek Josan, Fabio Miyajima, Rajiv Mohanraj, Arif Shukralla, Graeme J Sills, Anthony G Marson, Munir Pirmohamed
OBJECTIVE: Many different gene families are currently being investigated for their potential role in epilepsy and in the response to antiepileptic drugs. A common research challenge is identifying the members of a gene family that are most significantly dysregulated within the human epileptic focus, before taking them forward for resource-intensive functional studies. Published data about transcriptomic changes within the human epileptic focus remains incomplete. A need exists for an accurate in silico system for the prediction of dysregulated genes within the epileptic focus...
September 2016: Epilepsia
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