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ABCC4

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https://www.readbyqxmd.com/read/27895309/hepatocyte-specific-expression-of-an-oncogenic-variant-of-%C3%AE-catenin-results-in-cholestatic-liver-disease
#1
Ursula J Lemberger, Claudia Fuchs, Matthias Karer, Stefanie Haas, Tatjana Stojakovic, Christian Schöfer, Hanns-Ulrich Marschall, Fritz Wrba, Makoto M Taketo, Gerda Egger, Michael Trauner, Christoph H Österreicher
BACKGROUND: The Wnt/β-catenin signaling pathway plays a crucial role in embryonic development, tissue homeostasis, wound healing and malignant transformation in different organs including the liver. The consequences of continuous β-catenin signaling in hepatocytes remain elusive. RESULTS: Livers of Ctnnb1CA hep mice were characterized by disturbed liver architecture, proliferating cholangiocytes and biliary type of fibrosis. Serum ALT and bile acid levels were significantly increased in Ctnnb1CA hep mice...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27809359/renal-function-in-hiv-hbv-coinfected-and-hbv-monoinfected-patients-on-a-long-term-treatment-with-tenofovir-in-real-life-setting
#2
Laura Milazzo, Cristina Gervasoni, Felicia Stefania Falvella, Dario Cattaneo, Cristina Mazzali, Paola Ronzi, Francesca Binda, Stefania Cheli, Salvatore Sollima, Spinello Antinori
The HIV/HBV coinfection is likely associated with increased risk of kidney disease, due to the additional factors that may affect renal function in the HIV population. We aimed to evaluate renal toxicity in HIV/HBV and HBV monoinfected patients on long-term therapy with tenofovir (TDF) and to explore the association of polymorphisms in ATP-binding cassette (ABCC)2, ABCC4, ABCC10 with the development of renal dysfunction. From September 2006 to November 2014, 44 HIV/HBV co-infected and 34 HBV monoinfected patients were commenced on TDF...
November 3, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27764917/expression-and-regulation-of-prostaglandin-transporters-abcc1-abcc9-slco4c1-and-slco5a1-in-the-uterine-endometrium-during-the-estrous-cycle-and-pregnancy-in-pigs
#3
Hwanhee Jang, Yohan Choi, Inkyu Yoo, Jisoo Han, Minjeong Kim, Hakhyun Ka
Objective: Prostaglandins (PGs) function in various reproductive processes, including luteolysis, maternal pregnancy recognition, conceptus development, and parturition. Our earlier study has shown that PG transporters ABCC4 and SLCO2A1 are expressed in the uterine endometrium in pigs. Since several other PG transporters such as ABCC1, ABCC9, SLCO4C1, and SLCO5A1 are known to be present in the uterine endometrium, this study investigated the expression of these PG transporters in the porcine uterine endometrium and placenta...
October 19, 2016: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/27761583/several-adaptor-proteins-promote-intracellular-localisation-of-the-transporter-mrp4-abcc4-in-platelets-and-haematopoietic-cells
#4
Yvonne Schaletzki, Marie-Luise Kromrey, Susanne Bröderdorf, Elke Hammer, Markus Grube, Paul Hagen, Sonja Sucic, Michael Freissmuth, Uwe Völker, Andreas Greinacher, Bernhard H Rauch, Heyo K Kroemer, Gabriele Jedlitschky
The multidrug resistance protein 4 (MRP4/ABCC4) has been identified as an important transporter for signalling molecules including cyclic nucleotides and several lipid mediators in platelets and may thus represent a novel target to interfere with platelet function. Besides its localisation in the plasma membrane, MRP4 has been also detected in the membrane of dense granules in resting platelets. In polarised cells it is localised at the basolateral or apical plasma membrane. To date, the mechanism of MRP4 trafficking has not been elucidated; protein interactions may regulate both the localisation and function of this transporter...
October 20, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27664577/characterization-of-acquired-paclitaxel-resistance-of-breast-cancer-cells-and-involvement-of-abc-transporters
#5
Vlasta Němcová-Fürstová, Dana Kopperová, Kamila Balušíková, Marie Ehrlichová, Veronika Brynychová, Radka Václavíková, Petr Daniel, Pavel Souček, Jan Kovář
Development of taxane resistance has become clinically very important issue. The molecular mechanisms underlying the resistance are still unclear. To address this issue, we established paclitaxel-resistant sublines of the SK-BR-3 and MCF-7 breast cancer cell lines that are capable of long-term proliferation in 100nM and 300nM paclitaxel, respectively. Application of these concentrations leads to cell death in the original counterpart cells. Both sublines are cross-resistant to doxorubicin, indicating the presence of the MDR phenotype...
November 1, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27659809/polymorphic-variants-of-mrp4-abcc4-differentially-modulate-the-transport-of-methylated-arsenic-metabolites-and-physiological-organic-anions
#6
Mayukh Banerjee, Vanessa Marensi, Gwenaëlle Conseil, X Chris Le, Susan P C Cole, Elaine M Leslie
Broad inter-individual variation exists in susceptibility to arsenic-induced tumours, likely involving differences in the ability of individuals to eliminate this metalloid. We recently identified human multidrug resistance protein 4 (MRP4/ABCC4) as a novel pathway for the cellular export of dimethylarsinic acid (DMA(V)), the major urinary arsenic metabolite in humans, and the diglutathione conjugate of the highly toxic monomethylarsonous acid [MMA(GS)2]. These findings, together with the basolateral and apical membrane localization of MRP4 in hepatocytes and renal proximal tubule cells, respectively, suggest a role for MRP4 in the urinary elimination of hepatic arsenic metabolites...
September 19, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27649261/mir-pharmacogenetics-of-methotrexate-in-childhood-b-cell-acute-lymphoblastic-leukemia
#7
Leire Iparraguirre, Angela Gutierrez-Camino, Maitane Umerez, Idoia Martin-Guerrero, Itziar Astigarraga, Aurora Navajas, Ana Sastre, Nagore Garcia de Andoin, Africa Garcia-Orad
OBJECTIVES: Methotrexate (MTX), the key drug in childhood B-cell acute lymphoblastic leukemia (B-ALL) therapy, often causes toxicity. An association between genetic variants in MTX transport genes and toxicity has been found. It is known that these transporters are regulated by microRNAs (miRNAs), and miRNA single nucleotide polymorphisms (SNPs) interfere with miRNA levels or function. With regard to B-cell ALL, we have previously found rs56103835 in miR-323b that targets ABCC4 associated with MTX plasma levels...
November 2016: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/27628421/influence-of-genetic-polymorphisms-in-prostaglandin-e2-pathway-cox-2-hpgd-slco2a1-abcc4-on-the-risk-for-colorectal-adenoma-development-and-recurrence-after-polypectomy
#8
Carina Pereira, Sara Queirós, Ana Galaghar, Hugo Sousa, Ricardo Marcos-Pinto, Pedro Pimentel-Nunes, Catarina Brandão, Rui Medeiros, Mário Dinis-Ribeiro
OBJECTIVES: Deregulation of prostaglandin E2 (PGE2) levels reported in colorectal carcinogenesis contributes to key steps of cancer development. Our aim was to evaluate the influence of the genetic variability in COX-2/HPGD/SLCO2A1/ABCC4 PGE2 pathway genes on the development and recurrence of colorectal adenomas. METHODS: A case-control study was conducted gathering 480 unscreened individuals and 195 patients with personal history of adenomas. A total of 43 tagSNPs were characterized using the Sequenom platform or real-time PCR...
September 15, 2016: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/27613143/a-novel-exon-generates-ubiquitously-expressed-alternatively-spliced-new-transcript-of-mouse-abcc4-gene
#9
Sayeed Ur Rehman, Hassan Mubarak Ishqi, Mohammed Amir Husain, Tarique Sarwar, Mohammad Tabish
Abcc4 gene codes for a protein (ABCC4) involved in the transportation of different classes of drugs outside the cells. Various important drugs transported by ABCC4 include antiviral and anticancer drugs as well as endogenous molecules such as bile acids, cyclic nucleotides, folates, prostaglandins and steroids. Alternative splicing generates multiple mRNAs that encode protein isoforms having diverse functions. In this study, we have identified a novel transcript of mouse Abcc4 gene using a combination of bioinformatics and molecular biology techniques...
December 5, 2016: Gene
https://www.readbyqxmd.com/read/27569425/the-antiandrogen-flutamide-is-a-novel-aryl-hydrocarbon-receptor-ligand-that-disrupts-bile-acid-homeostasis-in-mice-through-induction-of-abcc4
#10
Xiaoxia Gao, Cen Xie, Yuanyuan Wang, Yuhong Luo, Tomoki Yagai, Dongxue Sun, Xuemei Qin, Kristopher W Krausz, Frank J Gonzalez
Flutamide (FLU), an oral, nonsteroidal antiandrogen drug used in the treatment of prostate cancer, is associated with idiosyncratic hepatotoxicity that sometimes causes severe liver damage, including cholestasis, jaundice, and liver necrosis. To understand the mechanism of toxicity, a combination of aryl hydrocarbon receptor (Ahr)-deficient (Ahr(-/-)) mice, primary hepatocytes, luciferase reporter gene assays, in silico ligand docking and ultra-performance chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics was used...
November 1, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27437769/molecular-gene-signature-and-prognosis-of-non-small-cell-lung-cancer
#11
Poyin Huang, Chiou-Ling Cheng, Ya-Hsuan Chang, Chia-Hsin Liu, Yi-Chiung Hsu, Jin-Shing Chen, Gee-Chen Chang, Bing-Ching Ho, Kang-Yi Su, Hsuan-Yu Chen, Sung-Liang Yu
The current staging system for non-small cell lung cancer (NSCLC) is inadequate for predicting outcome. Risk score, a linear combination of the values for the expression of each gene multiplied by a weighting value which was estimated from univariate Cox proportional hazard regression, can be useful. The aim of this study is to analyze survival-related genes with TaqMan Low-Density Array (TLDA) and risk score to explore gene-signature in lung cancer. A total of 96 NSCLC specimens were collected and randomly assigned to a training (n = 48) or a testing cohort (n = 48)...
July 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27402191/multidrug-resistance-associated-protein-4-mrp4-controls-ganciclovir-intracellular-accumulation-and-contributes-to-ganciclovir-induced-neutropenia-in-renal-transplant-patients
#12
REVIEW
Pierre-André Billat, Tahani Ossman, Franck Saint-Marcoux, Marie Essig, Jean-Philippe Rerolle, Nassim Kamar, Lionel Rostaing, Hannah Kaminski, Gabin Fabre, Michal Otyepka, Jean-Baptiste Woillard, Pierre Marquet, Patrick Trouillas, Nicolas Picard
Ganciclovir (GCV) is the cornerstone of cytomegalovirus prevention and treatment in transplant patients. It is associated with problematic adverse hematological effects in this population of immunosuppressed patients, which may lead to dose reduction thus favoring resistance. GCV crosses the membranes of cells, is activated by phosphorylation, and then stops the replication of viral DNA. Its intracellular accumulation might favor host DNA polymerase inhibition, hence toxicity. Following this hypothesis, we investigated the association between a selected panel of membrane transporter polymorphisms and the evolution of neutrophil counts in n=174 renal transplant recipients...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27354267/abcc4-abcc5-and-slc28a1-polymorphisms-host-genome-on-responses-of-chronic-hepatitis-b-patients-with-entecavir-treatment
#13
Man Yuan, Wenzhen Wang, Han Chen, Jiajie Lu, Min He, Cong Liu, Hong Tang, Lichun Wang
BACKGROUND: Nucleoside drug transporter polymorphisms play a significant role in patient responses to drugs. The aim was to investigate the effect of Multi-drug Resistance Protein 4, Multi-drug Resistance Protein 5, and human Concentrative Nucleoside Transporter 1 gene polymorphisms on the response to entecavir treatment in chronic hepatitis B patients. METHODS: A total of 324 chronic hepatitis B virus naive Chinese Han patients treated with entecavir 0.5 mg daily for 1 year were enrolled...
June 29, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27274832/analysis-of-abcg2-and-other-urate-transporters-in-uric-acid-homeostasis-in-chronic-kidney-disease-potential-role-of-remote-sensing-and-signaling
#14
Vibha Bhatnagar, Erin L Richard, Wei Wu, Caroline M Nievergelt, Michael S Lipkowitz, Janina Jeff, Adam X Maihofer, Sanjay K Nigam
BACKGROUND: In the setting of chronic kidney disease (CKD), altered extra-renal urate handling may be necessary to regulate plasma uric acid. The Remote Sensing and Signaling Hypothesis (Nigam S. What do drug transporters really do? Nat Rev Drug Discov 2015; 14: 29-44) suggests that multispecific solute carrier (SLC) and ATP-binding cassette (ABC) drug transporters in different tissues are part of an inter-organ communication system that maintains levels of urate and other metabolites after organ injury...
June 2016: Clinical Kidney Journal
https://www.readbyqxmd.com/read/27274726/a-cross-study-biomarker-signature-of-human-bronchial-epithelial-cells-infected-with-respiratory-syncytial-virus
#15
Luiz Gustavo Gardinassi
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children, elderly, and immunocompromised individuals. Despite of advances in diagnosis and treatment, biomarkers of RSV infection are still unclear. To understand the host response and propose signatures of RSV infection, previous studies evaluated the transcriptional profile of the human bronchial epithelial cell line-BEAS-2B-infected with different strains of this virus. However, the evolution of statistical methods and functional analysis together with the large amount of expression data provide opportunities to uncover novel biomarkers of inflammation and infections...
2016: Advances in Virology
https://www.readbyqxmd.com/read/27269636/efflux-transporter-variants-as-predictors-of-drug-toxicity-in-lung-cancer-patients-systematic-review-and-meta-analysis
#16
Zoulikha M Zaïr, Donald Rj Singer
UNLABELLED: Chemotherapeutic drugs are underutilized in lung cancer management due in part to serious adverse drug reactions (ADRs). AIM: With studies revealing an association between interindividual patient ADR variation and efflux transporter variants, we carried out a meta-analysis and systemic review, in order to highlight current knowledge regarding the strength of association between efflux transporter SNPs variants and chemotherapeutic-drug induced ADRs. MATERIALS & METHODS: Papers were sourced from MEDLINE, Cochrane Library, CINHL, EMBASE, Web of Knowledge, Scopus...
June 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27226732/mir-17-92a-1-cluster-host-gene-mir17hg-evaluation-and-response-to-neoadjuvant-chemoradiotherapy-in-rectal-cancer
#17
Chiara Molinari, Samanta Salvi, Flavia Foca, Nazario Teodorani, Luca Saragoni, Maurizio Puccetti, Alessandro Passardi, Stefano Tamberi, Andrea Avanzolini, Enrico Lucci, Daniele Calistri
Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is the gold standard for the treatment of patients with locally advanced rectal cancer (LARC). However, response is variable, and no predictive markers have been validated. The amplification of 13q31-34 seemed to distinguish between nonresponders and responders to NCRT. The miR-17-92a-1 cluster host gene (MIR17HG), which is involved in the development, progression, and aggressiveness of colorectal cancer, and the ABCC4 gene, an ATP-binding cassette transporter, are located at this region...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27199754/rifampin-regulation-of-drug-transporters-gene-expression-and-the-association-of-micrornas-in-human-hepatocytes
#18
Eric A Benson, Michael T Eadon, Zeruesenay Desta, Yunlong Liu, Hai Lin, Kimberly S Burgess, Matthew W Segar, Andrea Gaedigk, Todd C Skaar
UNLABELLED: Membrane drug transporters contribute to the disposition of many drugs. In human liver, drug transport is controlled by two main superfamilies of transporters, the solute carrier transporters (SLC) and the ATP Binding Cassette transporters (ABC). Altered expression of these transporters due to drug-drug interactions can contribute to differences in drug exposure and possibly effect. In this study, we determined the effect of rifampin on gene expression of hundreds of membrane transporters along with all clinically relevant drug transporters...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27148588/integrated-clinical-whole-genome-and-transcriptome-analysis-of-multisampled-lethal-metastatic-prostate-cancer
#19
G Steven Bova, Heini M L Kallio, Matti Annala, Kati Kivinummi, Gunilla Högnäs, Sergei Häyrynen, Tommi Rantapero, Virpi Kivinen, William B Isaacs, Teemu Tolonen, Matti Nykter, Tapio Visakorpi
We report the first combined analysis of whole-genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21). Whole-genome and transcriptome sequence was obtained from nine anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 yr before death. Transcriptome analysis revealed increased expression of androgen receptor (AR)-regulated genes in liver metastases that harbored an AR p...
May 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27068271/cysteinyl-leukotriene-receptor-1-2-antagonists-nonselectively-modulate-organic-anion-transport-by-multidrug-resistance-proteins-mrp1-4
#20
Mark A Csandl, Gwenaëlle Conseil, Susan P C Cole
Active efflux of both drugs and organic anion metabolites is mediated by the multidrug resistance proteins (MRPs). MRP1 (ABCC1), MRP2 (ABCC2), MRP3 (ABCC3), and MRP4 (ABCC4) have partially overlapping substrate specificities and all transport 17β-estradiol 17-(β-d-glucuronide) (E217βG). The cysteinyl leukotriene receptor 1 (CysLT1R) antagonist MK-571 inhibits all four MRP homologs, but little is known about the modulatory effects of newer leukotriene modifiers (LTMs). Here we examined the effects of seven CysLT1R- and CysLT2R-selective LTMs on E217βG uptake into MRP1-4-enriched inside-out membrane vesicles...
June 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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