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Abc transporters

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https://www.readbyqxmd.com/read/29456815/crispr-cas9-a-new-approach-to-successful-knockdown-of-abcb1-p-glycoprotein-and-reversal-of-chemosensitivity-in-human-epithelial-ovarian-cancer-cell-line
#1
Leyla Norouzi-Barough, Mohammadreza Sarookhani, Rasoul Salehi, Mohammadreza Sharifi, Sahar Moghbelinejad
Objectives: Multidrug resistance (MDR) is a major obstacle in the successful chemotherapy of ovarian cancer. Inhibition of P-glycoprotein (P-gp), a member of ATP-binding cassette (ABC) transporters, is a well-known strategy to overcome MDR in cancer. The aim of this study was to investigate the efficiency and ability of CRISPR/Cas9 genome editing technology to knockdown ABCB1 gene expression in adriamycin resistant (A2780/ADR) ovarian cancer cell line and evaluate the sensitivity changes to doxorubicin...
February 2018: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29455646/tyrosine-kinase-inhibitors-enhanced-the-efficacy-of-conventional-chemotherapeutic-agent-in-multidrug-resistant-cancer-cells
#2
REVIEW
Shaocong Wu, Liwu Fu
Multidrug resistance (MDR) triggered by ATP binding cassette (ABC) transporter such as ABCB1, ABCC1, ABCG2 limited successful cancer chemotherapy. Unfortunately, no commercial available MDR modulator approved by FDA was used in clinic. Tyrosine kinase inhibitors (TKIs) have been administrated to fight against cancer for decades. Almost TKI was used alone in clinic. However, drug combinations acting synergistically to kill cancer cells have become increasingly important in cancer chemotherapy as an approach for the recurrent resistant disease...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455001/evolution-and-molecular-mechanism-of-pitas-in-iron-transport-of-streptococcus-species
#3
Kun Cao, Jing Zhang, Xin-Yu Miao, Qiu-Xia Wei, Xin-Lu Zhao, Qing-Yu He, Xuesong Sun
Iron is an essential element for almost all bacteria. The iron ATP-binding cassette (ABC) transporters located on the cell membrane affects bacterial virulence and infection. Although a variety of Fe3+ -transporters have been found in bacteria, their evolutionary processes are rarely studied. Pneumococcal iron ABC transporter (PitA), a highly conserved Fe3+ -transporter in most pathogenic bacteria, influences the capsule formation and virulence of bacteria. However, multiple sequence alignment revealed that PitA is expressed in four different variants in bacteria, and the structural complexity of these variants increases progressively...
February 10, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29454971/overexpression-of-ptabcc1-contributes-to-mercury-tolerance-and-accumulation-in-arabidopsis-and-poplar
#4
Liping Sun, Yifeng Ma, Huihong Wang, Weipeng Huang, Xiaozhu Wang, Li Han, Wanmei Sun, Erqin Han, Bangjun Wang
Mercury (Hg) is a highly biotoxic heavy metal that contaminates the environment. Phytoremediation is a green technology for environmental remediation and is used to clean up Hg contaminated soil in recent years. In this study, we isolated an ATP-binding cassette (ABC) transporter gene PtABCC1 from Populus trichocarpa and overexpressed it in Arabidopsis and poplar. The transgenic plants conferred higher Hg tolerance than wild type (WT) plants, and overexpression of PtABCC1 could lead to 26-72% or 7-160% increase of Hg accumulation in Arabidopsis or poplar plants, respectively...
February 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29454809/the-hidden-lipoproteome-of-staphylococcus-aureus
#5
Anica Graf, Richard J Lewis, Stephan Fuchs, Martin Pagels, Susanne Engelmann, Katharina Riedel, Jan Pané-Farré
Lipoproteins are attached to the outer leaflet of the membrane by a di- or tri-acylglyceryl moiety and are thus positioned in the membrane-cell wall interface. Consequently, lipoproteins are involved in many surface associated functions, including cell wall synthesis, electron transport, uptake of nutrients, surface stress response, signal transduction, and they represent a reservoir of bacterial virulence factors. Inspection of 123 annotated Staphylococcus aureus genome sequences in the public domain revealed that this organism devotes about 2-3% of its coding capacity to lipoproteins, corresponding to about 70 lipoproteins per genome...
February 1, 2018: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/29453043/understanding-of-human-atp-binding-cassette-superfamily-and-novel-multidrug-resistance-modulators-to-overcome-mdr
#6
REVIEW
Imran Shair Mohammad, Wei He, Lifang Yin
Indeed, multi-drug resistance (MDR) is a significant obstacle to effective chemotherapy. The overexpression of ATP-binding cassette (ABC) membrane transporters is a principal cause of enhanced cytotoxic drug efflux and treatment failure in various types of cancers. At cellular level, the pumps of ABC family regulate the transportation of numerous substances including drugs in and out of the cells. In past, the overexpression of ABC pumps suggested a well-known mechanism of drug resistance in cancers as well as infectious diseases...
February 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29452934/evaluation-of-leader-peptides-that-affect-the-secretory-ability-of-a-multiple-bacteriocin-transporter-enkt
#7
Hirotoshi Sushida, Naoki Ishibashi, Takeshi Zendo, Pongtep Wilaipun, Vichien Leelawatcharamas, Jiro Nakayama, Kenji Sonomoto
EnkT is a novel ATP-binding cassette (ABC) transporter responsible for secretion of four bacteriocins, enterocins NKR-5-3A, C, D, and Z (Ent53A, C, D, and Z), produced by Enterococcus faecium NKR-5-3. It is generally recognized that the secretion of a bacteriocin requires a dedicated ABC transporter, although molecular mechanisms of this secretion are yet to be revealed. In order to characterize the unique ability of EnkT to secrete multiple bacteriocins, the role of N-terminal leader peptides of bacteriocin precursors was evaluated using Ent53C precursor as a model...
February 13, 2018: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/29445231/impact-of-nanoparticles-on-the-bacillus-subtilis-3610-competence
#8
Elise Eymard-Vernain, Sylvie Luche, Thierry Rabilloud, Cécile Lelong
Due to the physicochemical properties of nanoparticles, the use of nanomaterials increases every year in industrial and medical processes. At the same time, the increasing number of bacteria becoming resistant to many antibiotics, mostly by a horizontal gene transfer process, is a major public health concern. We herein report, for the first time, the role of nanoparticles in the physiological induction of horizontal gene transfer in bacteria. Besides the most well-known impacts of nanoparticles on bacteria, i...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29441961/clinically-relevant-interactions-of-anti-apoptotic-bcl-2-protein-inhibitors-with-abc-transporters
#9
E Ruzickova, R Janska, P Dolezel, P Mlejnek
In this work we studied clinically relevant interactions between the BH3 mimetics and the ABCB1 and ABCG2 transporters. We observed that the intracellular levels of ABT-263 and ABT-199, but not ABT-737, might be reduced by ABCB1 or ABCG2. Importantly, this effect was proportional to the transporter expression level. High transporter expression levels decreased the intracellular levels of ABT-263 and ABT-199 substantially. Low transporter expression levels, which are clinically relevant, affected the intracellular level of ABT-263 slightly but significantly, however, they failed to decrease the intracellular level of ABT-199 below the control level in parental cells...
December 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29437858/coarse-grained-molecular-dynamics-simulations-reveal-lipid-access-pathways-in-p-glycoprotein
#10
Estefania Barreto-Ojeda, Valentina Corradi, Ruo-Xu Gu, D Peter Tieleman
P-glycoprotein (P-gp) exports a broad range of dissimilar compounds, including drugs, lipids, and lipid-like molecules. Because of its substrate promiscuity, P-gp is a key player in the development of cancer multidrug resistance. Although P-gp is one of the most studied ABC transporters, the mechanism by which its substrates access the cavity remains unclear. In this study, we perform coarse-grained molecular dynamics simulations to explore possible lipid access pathways in the inward-facing conformation of P-gp embedded in bilayers of different lipid compositions...
February 6, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29432914/identification-of-the-heme-acquisition-system-in-vibrio-vulnificus-m2799
#11
Hiroaki Kawano, Katsushiro Miyamoto, Megumi Yasunobe, Masahiro Murata, Eri Yamahata, Ryo Yamaguchi, Yuta Miyaki, Takahiro Tsuchiya, Tomotaka Tanabe, Tatsuya Funahashi, Hiroshi Tsujibo
Vibrio vulnificus, the causative agent of serious, often fatal, infections in humans, requires iron for its pathogenesis. As such, it obtains iron via both vulnibactin and heme-mediated iron-uptake systems. In this study, we identified the heme acquisition system in V. vulnificus M2799. The nucleotide sequences of the genes encoding heme receptors HupA and HvtA and the ATP-binding cassette (ABC) transport system proteins HupB, HupC, and HupD were determined, and then used in the construction of deletion mutants developed from a Δics strain, which could not synthesize vulnibactin...
February 9, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29432725/energy-coupling-efficiency-in-the-type-i-abc-transporter-glnpq
#12
Jelger A Lycklama A Nijeholt, Ruslan Vietrov, Gea K Schuurman-Wolters, Bert Poolman
Solute transport via ABC importers involves receptor-mediated substrate binding, which is followed by ATP-driven translocation of the substrate across the membrane. How these steps are exactly initiated and coupled, and how much ATP it takes to complete a full transport cycle, are subject of debate. Here, we reconstitute the ABC importer GlnPQ in nanodiscs and in proteoliposomes and determine substrate-(in)dependent ATP hydrolysis and transmembrane transport. We determined the conformational states of the substrate-binding domains (SBDs) by single-molecule FRET measurements...
February 9, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29431891/independent-and-cooperative-regulation-of-staphylopine-biosynthesis-and-trafficking-by-fur-and-zur
#13
Clémentine Fojcik, Pascal Arnoux, Laurent Ouerdane, Marina Aigle, Laura Alfonsi, Elise Borezée-Durant
Staphylococcus aureus expresses the Cnt system implicated in the active transport of trace metals by synthesizing (CntKLM) and exporting (CntE) staphylopine, a metallophore chelating metals and then taken up by an ABC-transporter (CntABCDF). This machinery is encoded in the cntKLMABCDFE operon, preceded by a non-coding region (PcntK), and containing an internal promoter region (PcntA). PcntK comprises a Fur box followed by a Zur box, a sRNA transcription start and a repeated region, while PcntA comprises a Fur box that overlaps a Zur box...
February 12, 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29428416/genegini-assessment-via-the-gini-coefficient-of-reference-housekeeping-genes-and-diverse-human-transporter-expression-profiles
#14
Steve O'Hagan, Marina Wright Muelas, Philip J Day, Emma Lundberg, Douglas B Kell
The expression levels of SLC or ABC membrane transporter transcripts typically differ 100- to 10,000-fold between different tissues. The Gini coefficient characterizes such inequalities and here is used to describe the distribution of the expression of each transporter among different human tissues and cell lines. Many transporters exhibit extremely high Gini coefficients even for common substrates, indicating considerable specialization consistent with divergent evolution. The expression profiles of SLC transporters in different cell lines behave similarly, although Gini coefficients for ABC transporters tend to be larger in cell lines than in tissues, implying selection...
February 5, 2018: Cell Systems
https://www.readbyqxmd.com/read/29427702/high-brain-distribution-of-a-new-central-nervous-system-drug-candidate-despite-its-p-glycoprotein-mediated-efflux-at-the-mouse-blood-brain-barrier
#15
Camille Taccola, Sylvaine Cartot-Cotton, Delphine Valente, Pascal Barneoud, Catherine Aubert, Valérie Boutet, Fabienne Gallen, Murielle Lochus, Sophie Nicolic, Agnès Dodacki, Maria Smirnova, Salvatore Cisternino, Xavier Declèves, Fanchon Bourasset
Efficacy of drugs aimed at treating central nervous system (CNS) disorders rely partly on their ability to cross the cerebral endothelium, also called the blood-brain barrier (BBB), which constitutes the main interface modulating exchanges of compounds between the brain and blood. In this work, we used both, conventional pharmacokinetics (PK) approach and in situ brain perfusion technique to study the blood and brain PK of PKRinh, an inhibitor of the double-stranded RNA-dependent protein kinase (PKR) activation, in mice...
February 7, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29427638/ftsex-cwlo-regulates-biofilm-formation-by-a-plant-beneficial-rhizobacterium-bacillus-velezensis-sqr9
#16
Qing Li, Zunfeng Li, Xingxing Li, Liming Xia, Xuan Zhou, Zhihui Xu, Jiahui Shao, Qirong Shen, Ruifu Zhang
Bacillus velezensis strain SQR9 is a well-investigated rhizobacterium with an outstanding ability to colonize roots, enhance plant growth and suppress soil-borne diseases. The recognition that biofilm formation by plant-beneficial bacteria is crucial for their root colonization and function has resulted in increased interest in understanding molecular mechanisms related to biofilm formation. Here, we report that the gene ftsE, encoding the ATP-binding protein of an FtsEX ABC transporter, is required for efficient SQR9 biofilm formation...
February 7, 2018: Research in Microbiology
https://www.readbyqxmd.com/read/29425691/the-intracellular-region-of-silkworm-cadherin-like-protein-is-not-necessary-to-mediate-the-toxicity-of-bacillus-thuringiensis-cry1aa-and-cry1ab-toxins
#17
Haruka Endo, Satomi Adegawa, Shingo Kikuta, Ryoichi Sato
The cadherin-like protein in lepidopteran insects, known as a receptor for Bacillus thuringiensis Cry1A toxins, is a single-pass membrane protein that can be divided into extracellular and intracellular regions. The extracellular region is important for toxin binding and oligomerization, whereas the role of the intracellular region during Cry1A intoxication is unclear. In the present study, we generated a deletion mutant of Bombyx mori cadherin-like protein (BtR175) that lacked the intracellular region to investigate its role in mediating Cry1A toxicity...
February 6, 2018: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29425673/structural-stability-of-purified-human-cftr-is-systematically-improved-by-mutations-in-nucleotide-binding-domain-1
#18
Zhengrong Yang, Ellen Hildebrandt, Fan Jiang, Andrei A Aleksandrov, Netaly Khazanov, Qingxian Zhou, Jianli An, Andrew T Mezzell, Bala M Xavier, Haitao Ding, John R Riordan, Hanoch Senderowitz, John C Kappes, Christie G Brouillette, Ina L Urbatsch
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is an ABC transporter containing two transmembrane domains forming a chloride ion channel, and two nucleotide binding domains (NBD1 and NBD2). CFTR has presented a formidable challenge to obtain monodisperse, biophysically stable protein. Here we report a comprehensive study comparing effects of single and multiple NBD1 mutations on stability of both the NBD1 domain alone and on purified full length human CFTR. Single mutations S492P, A534P, I539T acted additively, and when combined with M470V, S495P, and R555K cumulatively yielded an NBD1 with highly improved structural stability...
February 6, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29423531/tissue-expression-pattern-of-abcg-transporter-indicates-functional-roles-in-reproduction-of-toxocara-canis
#19
Yong-Li Luo, Guang-Xu Ma, Yong-Fang Luo, Ce-Yan Kuang, Ai-Yun Jiang, Guo-Qing Li, Rong-Qiong Zhou
Toxocara canis is a zoonotic parasite with worldwide distribution. ATP-binding cassette (ABC) transporters are integral membrane proteins which involve in a range of biological processes in various organisms. In present study, the full-length coding sequence of abcg-5 gene of T. canis (Tc-abcg-5) was cloned and characterized. A 633 aa polypeptide containing two conserved Walker A and Walker B motifs was predicted from a continuous 1902 nt open reading frame. Quantitative real-time PCR was employed to determine the transcriptional levels of Tc-abcg-5 gene in adult male and female worms, which indicated high mRNA level of Tc-abcg-5 in the reproductive tract of adult female T...
February 8, 2018: Parasitology Research
https://www.readbyqxmd.com/read/29422490/dibutyl-phthalate-alters-the-metabolic-pathways-of-microbes-in-black-soils
#20
Weihui Xu, Yimin You, Zhigang Wang, Wenjing Chen, Jin Zeng, Xiaosong Zhao, Yunpeng Su
Dibutyl phthalate (DBP) is well known as a high-priority pollutant. This study explored the impacts of DBP on the metabolic pathways of microbes in black soils in the short term (20 days). The results showed that the microbial communities were changed in black soils with DBP. In nitrogen cycling, the abundances of the genes were elevated by DBP. DBP contamination facilitated 3'-phosphoadenosine-5'-phosphosulfate (PAPS) formation, and the gene flux of sulfate metabolism was increased. The total abundances of ABC transporters and the gene abundances of the monosaccharide-transporting ATPases MalK and MsmK were increased by DBP...
February 8, 2018: Scientific Reports
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