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Abc Transporter

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https://www.readbyqxmd.com/read/28073050/genome-wide-identification-of-atp-binding-cassette-abc-transporters-and-their-roles-in-response-to-polycyclic-aromatic-hydrocarbons-pahs-in-the-copepod-paracyclopina-nana
#1
Chang-Bum Jeong, Duck-Hyun Kim, Hye-Min Kang, Young Hwan Lee, Hui-Su Kim, Il-Chan Kim, Jae-Seong Lee
The ATP-binding cassette (ABC) protein superfamily is one of the largest gene families and is highly conserved in all domains. The ABC proteins play roles in several biological processes, including multi-xenobiotic resistance (MXR), by functioning as transporters in the cellular membrane. They also mediate the cellular efflux of a wide range of substrates against concentration gradients. In this study, 37 ABC genes belonging to eight distinct subfamilies were identified in the marine copepod Paracyclopina nana and annotated based on a phylogenetic analysis...
December 30, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/28069938/crystal-structure-and-mechanistic-basis-of-a-functional-homolog-of-the-antigen-transporter-tap
#2
Anne Nöll, Christoph Thomas, Valentina Herbring, Tina Zollmann, Katja Barth, Ahmad Reza Mehdipour, Thomas M Tomasiak, Stefan Brüchert, Benesh Joseph, Rupert Abele, Vincent Oliéric, Meitian Wang, Kay Diederichs, Gerhard Hummer, Robert M Stroud, Klaas M Pos, Robert Tampé
ABC transporters form one of the largest protein superfamilies in all domains of life, catalyzing the movement of diverse substrates across membranes. In this key position, ABC transporters can mediate multidrug resistance in cancer therapy and their dysfunction is linked to various diseases. Here, we describe the 2.7-Å X-ray structure of heterodimeric Thermus thermophilus multidrug resistance proteins A and B (TmrAB), which not only shares structural homology with the antigen translocation complex TAP, but is also able to restore antigen processing in human TAP-deficient cells...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28065893/pan-azole-resistant-candida-tropicalis-carrying-homozygous-erg11-mutations-at-position-k143r-a-new-emerging-superbug
#3
Mariana I D S Xisto, Rita D F Caramalho, Débora A S Rocha, Antonio Ferreira-Pereira, Bettina Sartori, Eliana Barreto-Bergter, Maria L Junqueira, Cornelia Lass-Flörl, Michaela Lackner
OBJECTIVES: Candidaemia is a public health problem mainly in hospitalized individuals worldwide. In Brazil, Candida albicans is the most prevalent species that causes candidaemia, followed by Candida tropicalis and Candida parapsilosis Few data on the abundance of antifungal resistance are available for Latin America. METHODS: We analysed the frequency of azole and echinocandin resistance in Candida isolates (n = 75) collected between 2012 and 2014 at the University Hospital of Federal University of Juiz de Fora (Brazil)...
January 8, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28063819/toxicological-interactions-of-silver-nanoparticles-and-non-essential-metals-in-human-hepatocarcinoma-cell-line
#4
Renata Rank Miranda, Arandi Ginane Bezerra, Ciro Alberto Oliveira Ribeiro, Marco Antônio Ferreira Randi, Carmen Lúcia Voigt, Lilian Skytte, Kaare Lund Rasmussen, Frank Kjeldsen, Francisco Filipak Neto
Toxicological interaction represents a challenge to toxicology, particularly for novel contaminants. There are no data whether silver nanoparticles (AgNPs), present in a wide variety of products, can interact and modulate the toxicity of ubiquitous contaminants, such as nonessential metals. In the current study, we investigated the toxicological interactions of AgNP (size=1-2nm; zeta potential=-23mV), cadmium and mercury in human hepatoma HepG2 cells. The results indicated that the co-exposures led to toxicological interactions, with AgNP+Cd being more toxic than AgNP+Hg...
January 4, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28062543/multiple-slc-and-abc-transporters-contribute-to-the-placental-transfer-of-entecavir
#5
Zhiyuan Ma, Xi Yang, Ting Jiang, Mengru Bai, Caihong Zheng, Su Zeng, Dongli Sun, Huidi Jiang
Entecavir (ETV), a nucleoside analogue with high efficacy against hepatitis B virus, is recommended as a first-line antiviral drug for the treatment of chronic hepatitis B. However, scant information is available on the use of ETV in pregnancy. To better understand the safety of ETV in pregnant women, we aimed to demonstrate whether ETV could permeate placental barrier and the underlying mechanism. Our study showed that small amount of ETV could permeate across placenta in mice. ETV accumulation in activated or non-activated BeWo cells (treated with or without forskolin) was sharply reduced in the presence of 100 μM of adenosine, cytidine and in Na+ free medium, indicating that nucleoside transporters possibly mediate the uptake of ETV...
January 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28062095/the-liver-transcriptome-of-suckermouth-armoured-catfish-pterygoplichthys-anisitsi-loricariidae-identification-of-expansions-in-defensome-gene-families
#6
Thiago E Parente, Daniel A Moreira, Maithê G P Magalhães, Paula C C de Andrade, Carolina Furtado, Brian J Haas, John J Stegeman, Mark E Hahn
Pterygoplichthys is a genus of related suckermouth armoured catfishes native to South America, which have invaded tropical and subtropical regions worldwide. Physiological features, including an augmented resistance to organic xenobiotics, may have aided their settlement in foreign habitats. The liver transcriptome of Pterygoplichthys anisitsi was sequenced and used to characterize the diversity of mRNAs potentially involved in the responses to natural and anthropogenic chemicals. In total, 66,642 transcripts were assembled...
January 3, 2017: Marine Pollution Bulletin
https://www.readbyqxmd.com/read/28058535/molecular-and-structural-characteristics-of-multidrug-resistance-associated-protein-7-in-chinese-liver-fluke-clonorchis-sinensis
#7
Fuhong Dai, Won Gi Yoo, Ji-Yun Lee, Yanyan Lu, Jhang Ho Pak, Woon-Mok Sohn, Sung-Jong Hong
Multidrug resistance-associated protein 7 (MRP7, ABCC10) is a C subfamily member of the ATP-binding cassette (ABC) superfamily. MRP7 is a lipophilic anion transporter that pumps endogenous and xenobiotic substrates from the cytoplasm to the extracellular milieu. Here, we cloned and characterized CsMRP7 as a novel ABC transporter from the Chinese liver fluke, Clonorchis sinensis. Full-length cDNA of CsMRP7 was 5174 nt, encoded 1636 amino acids (aa), and harbored a 147-bp 5'-untranslated region (5'-UTR) and 116-bp 3'-UTR...
January 5, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28058448/comparative-genomic-analysis-of-bacteriocin-producing-weissella-cibaria-110
#8
Shiao-Wen Li, Yi-Sheng Chen, Yun-Shien Lee, Chih-Hsien Yang, Sirinat Srionnual, Hui-Chung Wu, Chuan-Hsiung Chang
Weissella cibaria 110 was isolated from plaa-som, a Thai fermented fish product, and known to produce the weissellicin 110 bacteriocin. We carried out comprehensive comparative genomic analysis of W. cibaria 110 with four other non-bacteriocin-producing W. cibaria strains and identified potential antibiotic-resistant genes. We further identified a type III restriction-modification system, a TA system, and a bacteriocin gene cluster that are unique in W. cibaria 110. Genes related to bacteriocin biosynthesis are organized in clusters and are encoded with minimum genetic machinery consisting of structural cognate immunity genes, including ABC transporter and immunity protein...
January 5, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28056108/molecular-characterization-of-n-glycan-degradation-and-transport-in-streptococcus-pneumoniae-and-its-contribution-to-virulence
#9
Melissa Robb, Joanne K Hobbs, Shireen A Woodiga, Sarah Shapiro-Ward, Michael D L Suits, Nicholas McGregor, Harry Brumer, Hasan Yesilkaya, Samantha J King, Alisdair B Boraston
The carbohydrate-rich coating of human tissues and cells provide a first point of contact for colonizing and invading bacteria. Commensurate with N-glycosylation being an abundant form of protein glycosylation that has critical functional roles in the host, some host-adapted bacteria possess the machinery to process N-linked glycans. The human pathogen Streptococcus pneumoniae depolymerizes complex N-glycans with enzymes that sequentially trim a complex N-glycan down to the Man3GlcNAc2 core prior to the release of the glycan from the protein by endo-β-N-acetylglucosaminidase (EndoD), which cleaves between the two GlcNAc residues...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28053351/functional-analysis-of-the-abcs-of-eye-color-in-helicoverpa-armigera-with-crispr-cas9-induced-mutations
#10
Sher Afzal Khan, Michael Reichelt, David G Heckel
Many insect pigments are localized in subcellular pigment granules, and transport of pigment precursors from the cytoplasm is accomplished by ABC proteins. Drosophila melanogaster has three half-transporter genes (white, scarlet, and brown, all affecting eye pigments) and Bombyx mori has a fourth (ok). The White, Brown, Scarlet and Ok proteins each have one transmembrane and one cytoplasmic domain and they heterodimerize to form functional transporters with different substrate specificities. We used CRISPR/Cas9 to create somatic and germ-line knockout mutations of these four genes in the noctuid moth Helicoverpa armigera...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28052140/a-novel-zn2-cys6-transcription-factor-atrr-plays-a-key-role-in-an-azole-resistance-mechanism-of-aspergillus-fumigatus-by-co-regulating-cyp51a-and-cdr1b-expressions
#11
Daisuke Hagiwara, Daisuke Miura, Kiminori Shimizu, Sanjoy Paul, Ayumi Ohba, Tohru Gonoi, Akira Watanabe, Katsuhiko Kamei, Takahiro Shintani, W Scott Moye-Rowley, Susumu Kawamoto, Katsuya Gomi
Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in Aspergillus fungi including A. fumigatus, Aspergillus oryzae, and Aspergillus nidulans...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28051765/exploring-conformational-equilibria-of-a-heterodimeric-abc-transporter
#12
M Hadi Timachi, Cedric Aj Hutter, Michael Hohl, Tufa Assafa, Simon Böhm, Anshumali Mittal, Markus A Seeger, Enrica Bordignon
ABC exporters pump substrates across the membrane by coupling ATP-driven movements of nucleotide binding domains (NBDs) to the transmembrane domains (TMDs), which switch between inward- and outward-facing (IF, OF) orientations. DEER measurements on the heterodimeric ABC exporter TM287/288 from Thermotoga maritima, which contains a non-canonical ATP binding site, revealed that in the presence of nucleotides the transporter exists in an IF/OF equilibrium. While ATP binding was sufficient to partially populate the OF state, nucleotide trapping in the pre- or post-hydrolytic state was required for a pronounced conformational shift...
January 4, 2017: ELife
https://www.readbyqxmd.com/read/28050891/a-novel-mechanism-governing-the-transcriptional-regulation-of-abc-transporters-in-mdr-cancer-cells
#13
Jamie F Lu, Deep Pokharel, Mary Bebawy
P-glycoprotein (P-gp/ABCB1) and multidrug resistance-associated protein 1 (MRP1/ABCC1) are the main drug efflux transporters associated with treatment failure in cancer. Much attention has been focused on the molecular mechanisms regulating the expression of these transporters as a viable approach for identifying novel drug targets in circumventing cancer multidrug resistance (MDR) clinically. In this paper, we examine the role of miR-326 in the context of its intercellular transfer between cancer cells by extracellular membrane vesicles called microparticles (MPs)...
January 3, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28042952/uncoupling-protein-2-downregulation-by-hypoxia-through-repression-of-peroxisome-proliferator-activated-receptor-%C3%AE-promotes-chemoresistance-of-non-small-cell-lung-cancer
#14
Mingxing Wang, Guoyin Li, Zhiwei Yang, Lei Wang, Lei Zhang, Ting Wang, Yimeng Zhang, Shengli Zhang, Yong Han, Lintao Jia
Hypoxic microenvironment is critically involved in the response of non-small cell lung cancer (NSCLC) to chemotherapy, the mechanisms of which remain largely unknown. Here, we found that NSCLC patients exhibited increased chemotherapeutic resistance when complicated by chronic obstructive pulmonary disease (COPD), a critical cause of chronic hypoxemia. The downregulation of uncoupling protein 2 (UCP2), which is attributed to hypoxia-inducible factor 1 (HIF-1)-mediated suppression of the transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ), was involved in NSCLC chemoresistance, and predicted a poor survival rate of patients receiving routine chemotherapy...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035596/biosynthesis-and-uptake-of-glycine-betaine-as-cold-stress-response-to-low-temperature-in-fish-pathogen-vibrio-anguillarum
#15
Yue Ma, Qiyao Wang, Xiating Gao, Yuanxing Zhang
Fish pathogen Vibrio anguillarum, a mesophile bacterium, is usually found in estuarine and marine coastal ecosystems worldwide that pose a constant stress to local organism by its fluctuation in salinity as well as notable temperature change. Though V. anguillarum is able to proliferate while maintain its pathogenicity under low temperature (5-18°C), so far, coldadaption molecular mechanism of the bacteria is unknown. In this study, V. anguillarum was found possessing a putative glycine betaine synthesis system, which is encoded by betABI and synthesizes glycine betaine from its precursor choline...
January 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/28031414/inhibition-of-the-human-abc-efflux-transporters-p-gp-and-bcrp-by-the-bde-47-hydroxylated-metabolite-6-oh-bde-47-considerations-for-human-exposure
#16
Satori A Marchitti, Christopher S Mazur, Caleb M Dillingham, Swati Rawat, Anshika Sharma, Jason Zastre, John F Kenneke
High body burdens of polybrominated diphenyl ethers (PBDEs) in infants and young children have led to increased concern over their potential impact on human development. PBDE exposure can alter the expression of genes involved in thyroid homeostasis, including those of ATP-binding cassette (ABC) transporters, which mediate cellular xenobiotic efflux. However, little information exists on how PBDEs interact with ABC transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). The purpose of this study was to evaluate the interactions of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and its hydroxylated metabolite 6-OH-BDE-47 with P-gp and BCRP, using human MDR1- and BCRP-expressing membrane vesicles and stably transfected NIH-3T3-MDR1 and MDCK-BCRP cells...
October 23, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28029654/abcg2-confers-promotion-in-gastric-cancer-through-modulating-downstream-crkl-in-vitro-combining-with-biostatistics-mining
#17
Junqing Wang, Zhou Yunyun, Lu Wang, Xuehua Chen, Zhenggang Zhu
ABCG2, member of ATP-binding cassette (ABC) transporter family, is known as crucial regulator related to multi-drug resistance in human tumors and has recently been putatively studied as human carcinoma cell biomarker. While, effects of ABCG2 on human gastric cancer (GC) has not been illustrated thoroughly. In this study, by applying biostatistics mining methods, we observed that ABCG2 is frequently aberrantly expressed in GC patients through exploring dataset of GSE19826 in NCBI GEO database. Contemporary, extreme up-regulation of ABCG2 was discovered in both GC specimens and cell lines of our center, from which we observed high level of ABCG2 associated with GC clinicopathologic features and poor outcomes...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28028769/are-polymorphisms-in-genes-relevant-to-drug-disposition-predictors-of-susceptibility-to-drug-induced-liver-injury
#18
Ann K Daly
Despite considerable progress in identifying specific HLA alleles as genetic risk factors for some forms of drug-induced liver injury, progress in understanding whether genetic polymorphisms relevant to drug disposition also contribute to risk for developing this serious toxicity has been more limited. Evidence from both candidate-gene case control studies and genome-wide association studies is now discussed. In the case of genes relevant to drug metabolism, polymorphisms in cytochromes P450, UDP-glucuronosyltransferases, N-acetyltransferases and glutathione S-transferases as risk factors for DILI are assessed...
December 27, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/28028729/cardiovascular-ion-channel-inhibitor-drug-drug-interactions-with-p-glycoprotein
#19
Kaitlyn V Ledwitch, Arthur G Roberts
P-glycoprotein (Pgp) is an ATP-binding cassette (ABC) transporter that plays a major role in cardiovascular drug disposition by effluxing a chemically and structurally diverse range of cardiovascular therapeutics. Unfortunately, drug-drug interactions (DDIs) with the transporter have become a major roadblock to effective cardiovascular drug administration because they can cause adverse drug reactions (ADRs) or reduce the efficacy of drugs. Cardiovascular ion channel inhibitors are particularly susceptible to DDIs and ADRs with Pgp because they often have low therapeutic indexes and are commonly coadministered with other drugs that are also Pgp substrates...
December 27, 2016: AAPS Journal
https://www.readbyqxmd.com/read/28025333/modulation-of-bilirubin-neurotoxicity-by-the-abcb1-transporter-in-the-ugt1-lethal-mouse-model-of-neonatal-hyperbilirubinemia
#20
Luka Bočkor, Giulia Bortolussi, Simone Vodret, Alessandra Iaconcig, Jana Jašprová, Jaroslav Zelenka, Libor Vitek, Claudio Tiribelli, Andrés F Muro
Moderate neonatal jaundice is the most common clinical condition during newborn life. However, a combination of factors may result in acute hyperbilirubinemia, placing infants at risk of developing bilirubin encephalopathy and death by kernicterus. While most risk factors are known, the mechanisms acting to reduce susceptibility to bilirubin neurotoxicity remain unclear. The presence of modifier genes modulating the risk of developing bilirubin-induced brain damage is increasingly being recognised. The Abcb1 and Abcc1 members of the ABC family of transporters have been suggested to have an active role in exporting unconjugated bilirubin from the central nervous system into plasma...
December 25, 2016: Human Molecular Genetics
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