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https://www.readbyqxmd.com/read/28214518/potentiating-slc-transporter-activity-emerging-drug-discovery-opportunities
#1
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
#2
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
#3
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
#4
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
#5
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...
December 16, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27872146/organic-anion-transporter-2-oat2-an-enigmatic-human-solute-carrier
#6
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
#7
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
#8
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...
October 30, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27672436/slc-transporters-structure-function-and-drug-discovery
#9
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
#10
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
#11
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
#12
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...
August 9, 2016: 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
#13
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
#14
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
#15
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
#16
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
https://www.readbyqxmd.com/read/27385172/use-of-pet-imaging-to-evaluate-transporter-mediated-drug-drug-interactions
#17
Oliver Langer
Several membrane transporters belonging to the adenosine triphosphate-binding cassette (ABC) and solute carrier (SLC) families can transport drugs and drug metabolites and thereby exert an effect on drug absorption, distribution, and excretion, which may potentially lead to transporter-mediated drug-drug interactions (DDIs). Some transporter-mediated DDIs may lead to changes in organ distribution of drugs (eg, brain, liver, kidneys) without affecting plasma concentrations. Positron emission tomography (PET) is a noninvasive imaging method that allows studying of the distribution of radiolabeled drugs to different organs and tissues and is therefore the method of choice to quantitatively assess transporter-mediated DDIs on a tissue level...
July 2016: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27351344/monocarboxylate-transporters-therapeutic-targets-and-prognostic-factors-in-disease
#18
Robert S Jones, Marilyn E Morris
Solute carrier (SLC) transporters represent 52 families of membrane transport proteins that function in endogenous compound homeostasis and xenobiotic disposition, and have been exploited in drug delivery and therapeutic targeting strategies. In particular, the SLC16 family that encodes for the fourteen isoforms of the monocarboxylate transporter (MCT) family, play a significant role in the absorption, tissue distribution and clearance of both endogenous and exogenous compounds. MCTs are required for the transport of essential cell nutrients and for cellular metabolic and pH regulation...
June 28, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27302215/solute-carrier-41a3-encodes-for-a-mitochondrial-mg-2-efflux-system
#19
Lucia Mastrototaro, Alina Smorodchenko, Jörg R Aschenbach, Martin Kolisek, Gerhard Sponder
The important role of magnesium (Mg(2+)) in normal cellular physiology requires flexible, yet tightly regulated, intracellular Mg(2+) homeostasis (IMH). However, only little is known about Mg(2+) transporters of subcellular compartments such as mitochondria, despite their obvious importance for the deposition and reposition of intracellular Mg(2+) pools. In particular, knowledge about mechanisms responsible for extrusion of Mg(2+) from mitochondria is lacking. Based on circumstantial evidence, two possible mechanisms of Mg(2+) release from mitochondria were predicted: (1) Mg(2+) efflux coupled to ATP translocation via the ATP-Mg/Pi carrier, and (2) Mg(2+) efflux via a H(+)/Mg(2+) exchanger...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27256023/transcriptomic-analysis-identified-up-regulation-of-a-solute-carrier-transporter-and-udp-glucuronosyltransferases-in-dogs-with-aggressive-cutaneous-mast-cell-tumours
#20
Mery Giantin, Chiara Baratto, Laura Marconato, Marta Vascellari, Franco Mutinelli, Mauro Dacasto, Anna Granato
Gene expression analyses have been recently used in cancer research to identify genes associated with tumorigenesis and potential prognostic markers or therapeutic targets. In the present study, the transcriptome of dogs that had died because of mast cell tumours (MCTs) was characterised to identify a fingerprint having significant influence on prognosis determination and treatment selection. A dataset (GSE50433) obtained using a commercial canine DNA microarray platform was used. The transcriptome of seven biopsies obtained from dogs with histologically confirmed, surgically removed MCTs, treated with chemotherapy, and dead for MCT-related causes, was compared with the transcriptional portrait of 40 samples obtained from dogs with histologically confirmed, surgically removed MCTs and that were still alive at the end of the follow-up period...
June 2016: Veterinary Journal
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