Bioinformatics Analysis of the Expression of ATP Binding
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Design and Methods of the Prevalence and Pharmacogenomics of Tenofovir Nephrotoxicity in HIV-Positive Adults in South-Western Nigeria Study Muzamil O
Hassan et al. BMC Nephrology (2020) 21:436 https://doi.org/10.1186/s12882-020-02082-3 STUDY PROTOCOL Open Access Design and methods of the prevalence and pharmacogenomics of tenofovir nephrotoxicity in HIV-positive adults in south-western Nigeria study Muzamil O. Hassan1,2* , Raquel Duarte3, Victor O. Mabayoje4, Caroline Dickens3, Akeem O. Lasisi5 and Saraladevi Naicker6 Abstract Background: Individuals of African descent are at higher risk of developing kidney disease than their European counterparts, and HIV infection is associated with increased risk of nephropathy. Despite a safe renal profile in the clinical trials, long-term use of tenofovir disoproxil fumarate (TDF) has been associated with proximal renal tubulopathy although the underlying mechanisms remain undetermined. We aim to establish the prevalence of and risk factors for TDF-induced kidney tubular dysfunction (KTD) among HIV-I and II individuals treated with TDF in south-west Nigeria. Association between TDF-induced KTD and genetic polymorphisms in renal drug transporter genes and the APOL1 (Apolipoprotein L1) gene will be examined. Methods: This study has two phases. An initial cross-sectional study will screen 3000 individuals attending the HIV clinics in south-west Nigeria for KTD to determine the prevalence and risk factors. This will be followed by a case- control study of 400 KTD cases and 400 matched controls to evaluate single nucleotide polymorphism (SNP) associations. Data on socio-demographics, risk factors for kidney dysfunction and HIV history will be collected by questionnaire. Blood and urine samples for measurements of severity of HIV disease (CD4 count, viral load) and renal function (creatinine, eGFR, phosphate, uric acid, glucose) will also be collected. -
WO 2013/043130 Al 28 March 2013 (28.03.2013) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2013/043130 Al 28 March 2013 (28.03.2013) P O P C T (51) International Patent Classification: Building Level 5, Singapore 16875 1 (SG). KHOR, Chiea- C12Q 1/68 (2006.01) Chuen; Genome Institute of Singapore, 60 Biopolis Street, Genome, Singapore 138672 (SG). (21) International Application Number: PCT/SG2012/00035 1 (74) Agent: CHUNG, Jing Yeng; Marks & Clerk Singapore LLP, Tanjong Pagar, P.O Box 636, Singapore 9108 16 (22) International Filing Date: (SG). 24 September 2012 (24.09.2012) (81) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of national protection available): AE, AG, AL, AM, (26) Publication Language: English AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (30) Priority Data: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, 61/537,904 22 September 201 1 (22.09.201 1) US HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (71) Applicants: SINGAPORE HEALTH SERVICES PTE KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, LTD [SG/SG]; 31 Third Hospital Avenue, #03-03 Bowyer ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, Block C, Singapore 168753 (SG). AGENCY FOR SCI¬ NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, ENCE, TECHNOLOGY AND RESEARCH [SG/SG]; 1 RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, Fusionopolis Way, #20-10 Connexis, Singapore 138632 TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (SG). -
Developmental Differences in the Expression of ABC Transporters at Rat Brain Barrier Interfaces Following Chronic Exposure to Di
www.nature.com/scientificreports OPEN Developmental diferences in the expression of ABC transporters at rat brain barrier interfaces Received: 28 November 2018 Accepted: 28 March 2019 following chronic exposure to Published: xx xx xxxx diallyl sulfde Liam M. Koehn1, Katarzyna M. Dziegielewska1, Kjeld Møllgård 2, Elodie Saudrais3, Nathalie Strazielle3,4, Jean-Francois Ghersi-Egea3, Norman R. Saunders 1 & Mark D. Habgood1 Many pregnant women and prematurely born infants require medication for clinical conditions including cancer, cardiac defects and psychiatric disorders. In adults drug transfer from blood into brain is mostly restricted by efux mechanisms (ATP-binding cassette, ABC transporters). These mechanisms have been little studied during brain development. Here expression of eight ABC transporters (abcb1a, abcb1b, abcg2, abcc1, abcc2, abcc3, abcc4, abcc5) and activity of conjugating enzyme glutathione-s- transferase (GST) were measured in livers, brain cortices (blood-brain-barrier) and choroid plexuses (blood-cerebrospinal fuid, CSF, barrier) during postnatal rat development. Controls were compared to animals chronically injected (4 days, 200 mg/kg/day) with known abcb1a inducer diallyl sulfde (DAS). Results reveal both tissue- and age-dependent regulation. In liver abcb1a and abcc3 were up- regulated at all ages. In cortex abcb1a/b, abcg2 and abcc4/abcc5 were up-regulated in adults only, while in choroid plexus abcb1a and abcc2 were up-regulated only at P14. DAS treatment increased GST activity in livers, but not in cortex or choroid plexuses. Immunocytochemistry of ABC transporters at the CSF-brain interface showed that PGP and BCRP predominated in neuroepithelium while MRP2/4/5 were prominent in adult ependyma. These results indicate an age-related capacity of brain barriers to dynamically regulate their defence mechanisms when chronically challenged by xenobiotic compounds. -
Transcriptional and Post-Transcriptional Regulation of ATP-Binding Cassette Transporter Expression
Transcriptional and Post-transcriptional Regulation of ATP-binding Cassette Transporter Expression by Aparna Chhibber DISSERTATION Submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY in Pharmaceutical Sciences and Pbarmacogenomies in the Copyright 2014 by Aparna Chhibber ii Acknowledgements First and foremost, I would like to thank my advisor, Dr. Deanna Kroetz. More than just a research advisor, Deanna has clearly made it a priority to guide her students to become better scientists, and I am grateful for the countless hours she has spent editing papers, developing presentations, discussing research, and so much more. I would not have made it this far without her support and guidance. My thesis committee has provided valuable advice through the years. Dr. Nadav Ahituv in particular has been a source of support from my first year in the graduate program as my academic advisor, qualifying exam committee chair, and finally thesis committee member. Dr. Kathy Giacomini graciously stepped in as a member of my thesis committee in my 3rd year, and Dr. Steven Brenner provided valuable input as thesis committee member in my 2nd year. My labmates over the past five years have been incredible colleagues and friends. Dr. Svetlana Markova first welcomed me into the lab and taught me numerous laboratory techniques, and has always been willing to act as a sounding board. Michael Martin has been my partner-in-crime in the lab from the beginning, and has made my days in lab fly by. Dr. Yingmei Lui has made the lab run smoothly, and has always been willing to jump in to help me at a moment’s notice. -
ABC Transporter Subfamily D: Distinct Differences in Behavior Between ABCD1–3 and ABCD4 in Subcellular Localization, Function, and Human Disease
Hindawi Publishing Corporation BioMed Research International Volume 2016, Article ID 6786245, 11 pages http://dx.doi.org/10.1155/2016/6786245 Review Article ABC Transporter Subfamily D: Distinct Differences in Behavior between ABCD1–3 and ABCD4 in Subcellular Localization, Function, and Human Disease Kosuke Kawaguchi and Masashi Morita Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan Correspondence should be addressed to Kosuke Kawaguchi; [email protected] Received 24 June 2016; Accepted 29 August 2016 Academic Editor: Hiroshi Nakagawa Copyright © 2016 K. Kawaguchi and M. Morita. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ATP-binding cassette (ABC) transporters are one of the largest families of membrane-bound proteins and transport a wide variety of substrates across both extra- and intracellular membranes. They play a critical role in maintaining cellular homeostasis. To date, four ABC transporters belonging to subfamily D have been identified. ABCD1–3 and ABCD4 are localized to peroxisomes and lysosomes, respectively. ABCD1 and ABCD2 are involved in the transport of long and very long chain fatty acids (VLCFA) or their CoA-derivatives into peroxisomes with different substrate specificities, while ABCD3 is involved in the transport of branched chain acyl-CoA into peroxisomes. On the other hand, ABCD4 is deduced to take part in the transport of vitamin B12 from lysosomes into the cytosol. It is well known that the dysfunction of ABCD1 results in X-linked adrenoleukodystrophy, a severe neurodegenerative disease. -
Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in -
Interindividual Differences in the Expression of ATP-Binding
Supplemental material to this article can be found at: http://dmd.aspetjournals.org/content/suppl/2018/02/02/dmd.117.079061.DC1 1521-009X/46/5/628–635$35.00 https://doi.org/10.1124/dmd.117.079061 DRUG METABOLISM AND DISPOSITION Drug Metab Dispos 46:628–635, May 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Special Section on Transporters in Drug Disposition and Pharmacokinetic Prediction Interindividual Differences in the Expression of ATP-Binding Cassette and Solute Carrier Family Transporters in Human Skin: DNA Methylation Regulates Transcriptional Activity of the Human ABCC3 Gene s Tomoki Takechi, Takeshi Hirota, Tatsuya Sakai, Natsumi Maeda, Daisuke Kobayashi, and Ichiro Ieiri Downloaded from Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan (T.T., T.H., T.S., N.M., I.I.); Drug Development Research Laboratories, Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan (T.T.); and Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan (D.K.) Received October 19, 2017; accepted January 30, 2018 dmd.aspetjournals.org ABSTRACT The identification of drug transporters expressed in human skin and levels. ABCC3 expression levels negatively correlated with the methylation interindividual differences in gene expression is important for understanding status of the CpG island (CGI) located approximately 10 kilobase pairs the role of drug transporters in human skin. In the present study, we upstream of ABCC3 (Rs: 20.323, P < 0.05). The reporter gene assay revealed evaluated the expression of ATP-binding cassette (ABC) and solute carrier a significant increase in transcriptional activity in the presence of CGI. -
Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma
Cancers 2011, 3, 106-125; doi:10.3390/cancers3010106 OPEN ACCESS cancers ISSN 2072-6694 www.mdpi.com/journal/cancers Review Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma Wolfgang Hagmann 1, *, Ralf Faissner 1, Martina Schnölzer 2, Matthias Löhr 1,3 and Ralf Jesnowski 1,4 1 Clinical Cooperation Unit of Molecular Gastroenterology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; E-Mails: [email protected] (R.F.); [email protected] (M.L.); [email protected] (R.J.) 2 Functional Proteome Analysis, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; E-Mail: [email protected] 3 Department of Surgical Gastroenterology, CLINTEC, K53, Karolinska Institute, SE-14186 Stockholm, Sweden 4 Department of Medicine II, Medical Faculty of Mannheim, University of Heidelberg, Theodor- Kutzer-Ufer 1-3, D-68167 Mannheim, Germany * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +49 6221 424320; Fax: +49 6221 423359. Received: 1 December 2010; in revised form: 10 December 2010 / Accepted: 24 December 2010 / Published: 30 December 2010 Abstract: Pancreatic cancer ranks among the tumors most resistant to chemotherapy. Such chemoresistance of tumors can be mediated by various cellular mechanisms including dysregulated apoptosis or ineffective drug concentration at the intracellular target sites. In this review, we highlight recent advances in experimental chemotherapy underlining the role of cellular transporters in drug resistance. Such contribution to the chemoresistant phenotype of tumor cells or tissues can be conferred both by uptake and export transporters, as demonstrated by in vivo and in vitro data. -
Pattern of ABCC Transporter Gene Expression in Pediatric Patients with Relapsed Acute Lymphoblastic Leukemia
Reports of Biochemistry & Molecular Biology Vol.8, No.2, July 2019 Original article www.RBMB.net Pattern of ABCC Transporter Gene Expression in Pediatric Patients with Relapsed Acute Lymphoblastic Leukemia Narjes Mehrvar1, Hassan Abolghasemi2, Mohammad Reza Rezvany3, 4, Mohammad Esmaeil Akbari1, Javad Saberynejad5, Azim Mehrvar5, 6, Mohammad Ali Ehsani7, Mahyar Nourian6, Ibrahim Qaddoumi8, Abolfazl Movafagh*1, 9 Abstract Background: Abnormal expression of ABCC transporter genes has been associated with treatment failure in pediatric patients with acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate the expression pattern of ABCC1-6 and ABCC10 genes in Iranian pediatric patients with ALL relapse and determine the potential predictive value of determining ALL relapse from ABCC expression. Methods: Patients with ALL were divided into two separate groups, either the case group with relapsed ALL or the control group in which ALL patients have been in progression-free survival for at least 3 years A total of thirty-nine participants (23 with relapsed ALL; 16 controls) were enrolled over 26 months. To determine the levels of ABCC1-6 and ABCC10 transporter gene expression RT-PCR was used. Cumulative doses of the chemotherapy drugs, VCR, DNR and L-ASP, were calculated for each patient. Results: Our findings showed elevated expression of ABCC2-6 and decreased expression of ABCC1 and ABCC10 to be associated with an increased risk of ALL relapse. The mean-fold expression of ABCC2 was significantly increased in the ALL relapse group. Additionally, the expression pattern of the ABCC transporter genes was associated with high doses of three chemotherapy drugs, VCR, DNR and L-ASP. -
Role of Genetic Variation in ABC Transporters in Breast Cancer Prognosis and Therapy Response
International Journal of Molecular Sciences Article Role of Genetic Variation in ABC Transporters in Breast Cancer Prognosis and Therapy Response Viktor Hlaváˇc 1,2 , Radka Václavíková 1,2, Veronika Brynychová 1,2, Renata Koževnikovová 3, Katerina Kopeˇcková 4, David Vrána 5 , Jiˇrí Gatˇek 6 and Pavel Souˇcek 1,2,* 1 Toxicogenomics Unit, National Institute of Public Health, 100 42 Prague, Czech Republic; [email protected] (V.H.); [email protected] (R.V.); [email protected] (V.B.) 2 Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic 3 Department of Oncosurgery, Medicon Services, 140 00 Prague, Czech Republic; [email protected] 4 Department of Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, 150 06 Prague, Czech Republic; [email protected] 5 Department of Oncology, Medical School and Teaching Hospital, Palacky University, 779 00 Olomouc, Czech Republic; [email protected] 6 Department of Surgery, EUC Hospital and University of Tomas Bata in Zlin, 760 01 Zlin, Czech Republic; [email protected] * Correspondence: [email protected]; Tel.: +420-267-082-711 Received: 19 November 2020; Accepted: 11 December 2020; Published: 15 December 2020 Abstract: Breast cancer is the most common cancer in women in the world. The role of germline genetic variability in ATP-binding cassette (ABC) transporters in cancer chemoresistance and prognosis still needs to be elucidated. We used next-generation sequencing to assess associations of germline variants in coding and regulatory sequences of all human ABC genes with response of the patients to the neoadjuvant cytotoxic chemotherapy and disease-free survival (n = 105). -
Pharmacogenetic Analysis of High-Dose Methotrexate Treatment in Children with Osteosarcoma
www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 6), pp: 9388-9398 Research Paper Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma Marta Hegyi1, Adam Arany2,3, Agnes F. Semsei4, Katalin Csordas1, Oliver Eipel1, Andras Gezsi2,4, Nora Kutszegi1,4, Monika Csoka1, Judit Muller1, Daniel J. Erdelyi1, Peter Antal2, Csaba Szalai4, Gabor T. Kovacs1 1Second Department of Pediatrics, Semmelweis University, H-1094 Budapest, Tűzoltó utca 7-9, Hungary 2Department of Measurement and Information Systems, University of Technology and Economics, H-1111 Budapest, Műegyetem rkp. 3, Hungary 3Department of Organic Chemistry, Semmelweis University, H-1092 Budapest, Hőgyes Endre u. 7, Hungary 4Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, Nagyvárad tér 4, Hungary Correspondence to: Gabor T. Kovacs, email: [email protected] Keywords: osteosarcoma, methotrexate, toxicity, SNP, Bayesian network-based Bayesian multilevel analysis of relevance (BN-BMLA) Received: February 18, 2016 Accepted: August 09, 2016 Published: August 23, 2016 ABSTRACT Inter-individual differences in toxic symptoms and pharmacokinetics of high- dose methotrexate (MTX) treatment may be caused by genetic variants in the MTX pathway. Correlations between polymorphisms and pharmacokinetic parameters and the occurrence of hepato- and myelotoxicity were studied. Single nucleotide polymorphisms (SNPs) of the ABCB1, ABCC1, ABCC2, ABCC3, ABCC10, ABCG2, GGH, SLC19A1 and NR1I2 genes were analyzed in 59 patients with osteosarcoma. Univariate association analysis and Bayesian network-based Bayesian univariate and multilevel analysis of relevance (BN-BMLA) were applied. Rare alleles of 10 SNPs of ABCB1, ABCC2, ABCC3, ABCG2 and NR1I2 genes showed a correlation with the pharmacokinetic values and univariate association analysis. -
Single Nucleotide Polymorphism in ABCG2 Is Associated with Irinotecan-Induced Severe Myelosuppression
Journal of Human Genetics (2009) 54, 572–580 & 2009 The Japan Society of Human Genetics All rights reserved 1434-5161/09 $32.00 www.nature.com/jhg ORIGINAL ARTICLE Single nucleotide polymorphism in ABCG2 is associated with irinotecan-induced severe myelosuppression Pei-Chieng Cha1, Taisei Mushiroda2, Hitoshi Zembutsu1, Hiromasa Harada3, Noriyuki Shinoda3, Shunji Kawamoto3, Rai Shimoyama3, Toshihiko Nishidate4, Tomohisa Furuhata4, Kazuaki Sasaki4, Koichi Hirata4 and Yusuke Nakamura1 Irinotecan is an anti-neoplastic agent that is widely used for treating colorectal and lung cancers, but often causes toxicities such as severe myelosuppression and diarrhea. In this study, we performed a two-stage case–control association study for irinotecan-induced severe myelosuppression (grades 3 and 4). In the first stage, 23 patients who developed severe myelosuppression and 58 patients who did not develop any toxicity were examined for 170 single nucleotide polymorphisms (SNPs) in 14 genes involved in the metabolism and transport of irinotecan. A total of five SNPs were identified to show the possible association with severe myelosuppression (PFishero0.01) and were further examined in 7 cases and 20 controls in the second stage of the study. An intronic SNP, rs2622604, in ABCG2 showed PFisher¼0.0419 in the second stage and indicated a significant association with severe myelosuppression in the combined study (PFisher¼0.000237; PCorrected¼0.036). Although only limited subjects were investigated, our results suggested that a genetic polymorphism in ABCG2