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ABCC4

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https://www.readbyqxmd.com/read/29724294/abcc2-rs2273697-is-associated-with-valproic-acid-concentrations-in-patients-with-epilepsy-on-valproic-acid-monotherapy
#1
Juan Chen, Qi-Biao Su, Yu-Qian Tao, Jia-Ming Qin, Yi Zhou, Shan Zhou, Hong-Liang Li, Zhuo-Jia Chen, Ya-Fang Zhou, Lie-Min Zhou, Xue-Ding Wang, Min Huang
Valproic acid (VPA), a widely used antiepileptic drug, is characterized by intensive inter-individual variability in concentration. Both efflux and influx transporters are reported to play important roles in the disposition of VPA, however, no comprehensive investigation into the association of the single nucleotide polymorphism (SNP) in ABC/SLC families with VPA concentration are reported. In the present study, we investigated the association of 12 SNPs in ABCC2, ABCC4, ABCG2, MCT1, MCT2, and OATP2B1 in 187 Chinese patients with epilepsy on VPA monotherapy with the trough concentrations of VPA...
May 1, 2018: Die Pharmazie
https://www.readbyqxmd.com/read/29683944/slco1b1-polymorphisms-are-associated-with-drug-intolerance-in-childhood-leukemia-maintenance-therapy
#2
İrem Eldem, Duygu Yavuz, Özge Cumaoğullari, Talia İleri, Elif Ünal İnce, Mehmet Ertem, Beyza Doğanay Erdoğan, Recep Bindak, Hilal Özdağ, N Lale Şatiroğlu-Tufan, L Zümrüt Uysal
BACKGROUND: Therapy discontinuations and toxicities occur because of significant interindividual variations in 6-mercaptopurine (6-MP) and methotrexate (MTX) response during maintenance therapy of childhood acute lymphoblastic leukemia (ALL). 6-MP/MTX intolerance in some of the patients cannot be explained by thiopurine S-methyl transferase (TPMT) gene variants. In this study, we aimed to investigate candidate pharmacogenetic determinants of 6-MP and MTX intolerance in Turkish ALL children...
April 20, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29675872/identification-and-quantification-of-blood-brain-barrier-transporters-in-isolated-rat-brain-microvessels
#3
Hajar Al Feteisi, Zubida M Al-Majdoub, Brahim Achour, Narciso Couto, Amin Rostami-Hodjegan, Jill Barber
The blood-brain barrier (BBB) maintains brain homeostasis by tightly regulating the exchange of molecules with systemic circulation. It consists primarily of microvascular endothelial cells surrounded by astrocytic endfeet, pericytes, and microglia. Understanding the make-up of transporters in rat BBB is essential to the translation of pharmacological and toxicological observations into humans. In this study, experimental workflows are presented in which the optimization of (a) isolation of rat brain microvessels, (b) enrichment of endothelial cells, and (c) extraction and digestion of proteins were evaluated, followed by identification and quantification of BBB proteins...
April 20, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29616130/co-expression-of-atp-binding-cassette-transporters-is-associated-with-poor-prognosis-in-acute-myeloid-leukemia
#4
Bei Liu, Li-Jun Li, Xia Gong, Wei Zhang, Hui Zhang, Li Zhao
Chemotherapy failure remains a challenge when treating patients with acute myeloid leukemia (AML), who often suffer from persistent or relapsed disease. The multidrug resistance (MDR) mediated by efflux transporters of the ATP binding cassette (ABC) superfamily is a major obstacle for successful chemotherapy. The present study aimed to elucidate whether the expression of ABC transporters was associated with prognostic factors and responses to chemotherapy in patients with AML, with particular focus on whether co-expression of multiple ABC transporters resulted in a worse prognosis...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29602831/bioengineered-ncrnas-selectively-change-cellular-mirnome-profiles-for-cancer-therapy
#5
Pui Yan Ho, Zhijian Duan, Neelu Batra, Joseph L Jilek, Mei-Juan Tu, Jing-Xin Qiu, Zihua Hu, Theodore Wun, Primo N Lara, Ralph W DeVere White, Hong-Wu Chen, Ai-Ming Yu
Noncoding RNAs (ncRNAs) produced in live cells may better reflect intracellular ncRNAs for research and therapy. Attempts were made to produce biological ncRNAs, but at low yield or success rate. Here we first report a new ncRNA bioengineering technology, using more stable ncRNA carrier (nCAR) containing a pre-miR-34a derivative identified by rational design and experimental validation. This approach offered a remarkable higher-level expression (40-80% of total RNAs) of recombinant ncRNAs in bacteria, and gave an 80% success rate (33 out of 42 ncRNAs)...
March 30, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29587409/nose-to-brain-delivery-of-antiviral-drugs-a-way-to-overcome-their-active-efflux
#6
REVIEW
Alessandro Dalpiaz, Barbara Pavan
Although several viruses can easily infect the central nervous system (CNS), antiviral drugs often show dramatic difficulties in penetrating the brain from the bloodstream since they are substrates of active efflux transporters (AETs). These transporters, located in the physiological barriers between blood and the CNS and in macrophage membranes, are able to recognize their substrates and actively efflux them into the bloodstream. The active transporters currently known to efflux antiviral drugs are P-glycoprotein (ABCB1 or P-gp or MDR1), multidrug resistance-associated proteins (ABCC1 or MRP1, ABCC4 or MRP4, ABCC5 or MRP5), and breast cancer resistance protein (ABCG2 or BCRP)...
March 26, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29580174/effect-of-hydrochlorothiazide-on-serum-uric-acid-concentration-a-genome-wide-association-study
#7
Eero M Ala-Mutka, Jenni M Rimpelä, Frej Fyhrquist, Kimmo K Kontula, Timo P Hiltunen
AIM: To recognize genetic associations of hydrochlorothiazide-induced change in serum uric acid (SUA) concentration. PATIENTS & METHODS: We conducted a genome-wide association study on hydrochlorothiazide-induced change in SUA in 214 Finnish men from the GENRES study. Replication analyses were performed in 465 Finns from the LIFE study. RESULTS: In GENRES, we identified 31 loci associated with hydrochlorothiazide-induced change in SUA at p < 5 × 10-5 ...
March 27, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29530601/structural-patterns-of-the-human-abcc4-mrp4-exporter-in-lipid-bilayers-rationalize-clinically-observed-polymorphisms
#8
B Chantemargue, F Di Meo, K Berka, N Picard, H Arnion, M Essig, P Marquet, M Otyepka, P Trouillas
The ABCC4/MRP4 exporter has a clinical impact on membrane transport of a broad range of xenobiotics. It is expressed at key locations for drug disposition or effects such as in the liver, the kidney and blood cells. Several polymorphisms and mutations (e.g., p.Gly187Trp) leading to MRP4 dysfunction are associated with an increased risk of toxicity of some drugs. So far, no human MRP4 structure has been elucidated, precluding rationalization of these dysfunctions at a molecular level. We constructed atomistic model of the wild type (WT) MRP4 and the p...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29514827/beyond-competitive-inhibition-regulation-of-abc-transporters-by-kinases-and-protein-protein-interactions-as-potential-mechanisms-of-drug-drug-interactions
#9
Rebecca R Crawford, Praveen K Potukuchi, Erin G Schuetz, John D Schuetz
ATP-binding cassette (ABC) transporters are transmembrane efflux transporters mediating the extrusion of an array of substrates ranging from amino acids and lipids to xenobiotics, and many therapeutic compounds, including anticancer drugs. The ABC transporters are also recognized as important contributors to pharmacokinetics, especially in drug-drug interactions and adverse drug effects. Drugs and xenobiotics, as well as pathologic conditions, can influence the transcription of ABC transporters, or modify their activity or intracellular localization...
May 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29304533/release-of-platelet-derived-sphingosine-1-phosphate-involves-multidrug-resistance-protein-4-mrp4-abcc4-and-is-inhibited-by-statins
#10
Katja Vogt, Shailaja Mahajan-Thakur, Robert Wolf, Susanne Bröderdorf, Conny Vogel, Andreas Böhm, Christoph A Ritter, Markus Gräler, Stefan Oswald, Andreas Greinacher, Heyo K Kroemer, Gabriele Jedlitschky, Bernhard H Rauch
Sphingosine-1-phosphate (S1P) is a potent lipid mediator released from activated platelets by an adenosine triphosphate (ATP)-dependent export mechanism. A candidate transport protein is the multidrug resistance protein 4 (MRP4/ABCC4), an ATP-dependent transporter highly expressed in platelets. Furthermore, several statins are known to affect platelet functions and exhibit antithrombotic properties. This study determines the involvement of MRP4 in the transport of S1P and a possible interference by statins...
January 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29284392/mrp4-abcc4-as-a-new-therapeutic-target-meta-analysis-to-determine-camp-binding-sites-as-a-tool-for-drug-design
#11
Agustín Yaneff, Ana Sahores, Natalia Gomez, Alejandro Carozzo, Carina Shayo, Carlos Davio
MRP4 transports multiple endogenous and exogenous substances and is critical not only for detoxification but also in the homeostasis of several signaling molecules. Its dysregulation has been reported in numerous pathological disorders, thus MRP4 appears as an attractive therapeutic target. However, the efficacy of MRP4 inhibitors is still controversial. The design of specific pharmacological agents with the ability to selectively modulate the activity of this transporter or modify its affinity to certain substrates represents a challenge in current medicine and chemical biology...
December 29, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29246027/recent-advances-on-uric-acid-transporters
#12
REVIEW
Liuqing Xu, Yingfeng Shi, Shougang Zhuang, Na Liu
Uric acid is the product of purine metabolism and its increased levels result in hyperuricemia. A number of epidemiological reports link hyperuricemia with multiple disorders, such as kidney diseases, cardiovascular diseases and diabetes. Recent studies also showed that expression and functional changes of urate transporters are associated with hyperuricemia. Uric acid transporters are divided into two categories: urate reabsorption transporters, including urate anion transporter 1 (URAT1), organic anion transporter 4 (OAT4) and glucose transporter 9 (GLUT9), and urate excretion transporetrs, including OAT1, OAT3, urate transporter (UAT), multidrug resistance protein 4 (MRP4/ABCC4), ABCG-2 and sodium-dependent phosphate transport protein...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29222397/indoxyl-sulfate-upregulates-liver-p-glycoprotein-expression-and-activity-through-aryl-hydrocarbon-receptor-signaling
#13
Tacy Santana Machado, Stéphane Poitevin, Pascale Paul, Nathalie McKay, Noémie Jourde-Chiche, Tristan Legris, Annick Mouly-Bandini, Françoise Dignat-George, Philippe Brunet, Rosalinde Masereeuw, Stéphane Burtey, Claire Cerini
In patients with CKD, not only renal but also, nonrenal clearance of drugs is altered. Uremic toxins could modify the expression and/or activity of drug transporters in the liver. We tested whether the uremic toxin indoxyl sulfate (IS), an endogenous ligand of the transcription factor aryl hydrocarbon receptor, could change the expression of the following liver transporters involved in drug clearance: SLC10A1 , SLC22A1 , SLC22A7 , SLC47A1 , SLCO1B1 , SLCO1B3 , SLCO2B1 , ABCB1 , ABCB11 , ABCC2 , ABCC3 , ABCC4 , ABCC6 , and ABCG2 We showed that IS increases the expression and activity of the efflux transporter P-glycoprotein (P-gp) encoded by ABCB1 in human hepatoma cells (HepG2) without modifying the expression of the other transporters...
March 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29146910/an-unexpected-protein-interaction-promotes-drug-resistance-in-leukemia
#14
Aaron Pitre, Yubin Ge, Wenwei Lin, Yao Wang, Yu Fukuda, Jamshid Temirov, Aaron H Phillips, Jennifer L Peters, Yiping Fan, Jing Ma, Amanda Nourse, Chandrima Sinha, Hai Lin, Richard Kriwacki, James R Downing, Tanja A Gruber, Victoria E Centonze, Anjaparavanda P Naren, Taosheng Chen, John D Schuetz
The overall survival of patients with acute myeloid leukemia (AML) is poor and identification of new disease-related therapeutic targets remains a major goal for this disease. Here we show that expression of MPP1, a PDZ-domain-containing protein, highly correlated with ABCC4 in AML, is associated with worse overall survival in AML. Murine hematopoietic progenitor cells overexpressing MPP1 acquired the ability to serially replate in methylcellulose culture, a property crucially dependent upon ABCC4. The highly conserved PDZ-binding motif of ABCC4 is required for ABCC4 and MPP1 to form a protein complex, which increased ABCC4 membrane localization and retention, to enhance drug resistance...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29103996/inhibition-of-abcc4-potentiates-combination-beta-agonist-and-glucocorticoid-responses-in-human-airway-epithelial-cells
#15
Ryan D Huff, Christopher F Rider, Dong Yan, Robert Newton, Mark A Giembycz, Chris Carlsten, Jeremy A Hirota
No abstract text is available yet for this article.
March 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29061583/bioengineered-nrf2-sirna-is-effective-to-interfere-with-nrf2-pathways-and-improve-chemosensitivity-of-human-cancer-cells
#16
Peng-Cheng Li, Mei-Juan Tu, Pui Yan Ho, Joseph L Jilek, Zhijian Duan, Qian-Yu Zhang, Ai-Xi Yu, Ai-Ming Yu
The nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a transcription factor in the regulation of many oxidative enzymes and efflux transporters critical for oxidative stress and cellular defense against xenobiotics. NRF2 is dysregulated in patient osteosarcoma (OS) tissues and correlates with therapeutic outcomes. Nevertheless, research on the NRF2 regulatory pathways and its potential as a therapeutic target is limited to the use of synthetic small interfering RNA (siRNA) carrying extensive artificial modifications...
January 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29061086/pharmacogenetics-based-population-pharmacokinetic-analysis-of-tenofovir-in-thai-hiv-infected-patients
#17
Kanokrat Rungtivasuwan, Anchalee Avihingsanon, Narukjaporn Thammajaruk, Siwaporn Mitruk, David M Burger, Kiat Ruxrungtham, Chonlaphat Sukasem, Baralee Punyawudho
AIM: To develop a population pharmacokinetic model and identify sources of variability, genetic and nongenetic factors, of tenofovir. METHODS: The ABCC2 and ABCC4 polymorphisms were genotyped in 342 patients. A nonlinear mixed effects model was used to develop the population pharmacokinetic model and investigate the influence of these polymorphisms and other patient specific covariates on the pharmacokinetics of tenofovir. RESULTS: The estimated glomerular filtration rate calculated by the Cockcroft and Gault equation, concomitant use of lopinavir/ritonavir and ABCC4 3463A>G polymorphism were associated with tenofovir apparent oral clearance (CL/F)...
October 24, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28975866/slco1a2-slco1b1-and-slco2b1-polymorphisms-influences-chloroquine-and-primaquine-treatment-in-plasmodium-vivax-malaria
#18
Vinicius A Sortica, Juliana D Lindenau, Maristela G Cunha, Maria Deise O Ohnishi, Ana Maria R Ventura, Ândrea Kc Ribeiro-Dos-Santos, Sidney Eb Santos, Luciano Sp Guimarães, Mara H Hutz
AIM: The association of transporters gene polymorphisms with chloroquine/primaquine malaria treatment response was investigated in a Brazilian population. PATIENTS & METHODS: Totally, 164 Plasmodium vivax malaria infected patients were included. Generalized estimating equations were performed to determine gene influences on parasitemia and/or gametocytemia clearance over treatment time. RESULTS: Significant interaction between SLCO2B1 genotypes and treatment over time for parasitemia clearance rate on day 2 were observed (p FDR = 0...
October 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28960749/detoxification-of-ivermectin-by-atp-binding-cassette-transporter-c4-and-cytochrome-p450-monooxygenase-6cj1-in-the-human-body-louse-pediculus-humanus-humanus
#19
J H Kim, K J Gellatly, B Lueke, M Kohler, R Nauen, E Murenzi, K S Yoon, J M Clark
We previously observed that ivermectin-induced detoxification genes, including ATP binding cassette transporter C4 (PhABCC4) and cytochrome P450 6CJ1 (CYP6CJ1) were identified from body lice following a brief exposure to a sublethal dose of ivermectin using a non-invasive induction assay. In this current study, the functional properties of PhABCC4 and CYP6CJ1 were investigated after expression in either X. laevis oocytes or using a baculovirus expression system, respectively. Efflux of [3 H]-9-(2-phosphonomethoxyethyl) adenine ([3 H]-PMEA), a known ABCC4 substrate in humans, was detected from PhABCC4 cRNA-injected oocytes by liquid scintillation spectrophotometric analysis and PhABCC4 expression in oocytes was confirmed using ABC transporter inhibitors...
February 2018: Insect Molecular Biology
https://www.readbyqxmd.com/read/28959040/endoplasmic-reticulum-stress-preconditioning-modifies-intracellular-mercury-content-by-upregulating-membrane-transporters
#20
Fusako Usuki, Masatake Fujimura, Akio Yamashita
Endoplasmic reticulum (ER) stress preconditioning protects cells against methylmercury (MeHg) cytotoxicity by inducing integrated stress responses such as eIF2α phosphorylation, ATF4 accumulation, and nonsense-mediated mRNA decay (NMD) suppression. Here we demonstrated that ER stress preconditioning results in the upregulation of membrane transporters, leading to a decrease in intracellular mercury content. Our analyses showed that ER stress preconditioning upregulated the expression of methionine transporters that affect the cellular influx of MeHg, LAT1, LAT3, and SNAT2; and a membrane transporter that affects the efflux of MeHg, ABCC4, in MeHg-susceptible myogenic cells...
September 28, 2017: Scientific Reports
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