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Abc transporters

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https://www.readbyqxmd.com/read/27916559/rhinacanthin-c-enhances-doxorubicin-cytotoxicity-via-inhibiting-the-functions-of-p-glycoprotein-and-mrp2-in-breast-cancer-cells
#1
Tassarut Chaisit, Pongpun Siripong, Suree Jianmongkol
Rhinacanthin-C is a major bioactive naphthoquinone ester found in Rhinacanthus nasutus Kurz (Acanthaceae). This compound has potential therapeutic value as an anticancer and antiviral agent. In this study, we investigated an enhancement effect of rhinacanthin-C on doxorubicin cytotoxicity in human breast cancer cell lines and the involvement of the ABC drug efflux transporters. The cytotoxicity was determined by an MTT assay. Combination between doxorubicin and rhinacanthin-C at their non-cytotoxic concentrations when giving each compound alone significantly reduced cell viability in MCF-7 and MCF-7/DOX resistant cells...
December 1, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27913277/specific-stabilization-of-cftr-by-phosphatidylserine
#2
Ellen Hildebrandt, Netaly Khazanov, John C Kappes, Qun Dai, Hanoch Senderowitz, Ina L Urbatsch
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR, ABCC7) is a plasma membrane chloride ion channel in the ABC transporter superfamily. CFTR is a key target for cystic fibrosis drug development, and its structural elucidation would advance those efforts. However, the limited in vivo and in vitro stability of the protein, particularly its nucleotide binding domains, has made structural studies challenging. Here we demonstrate that phosphatidylserine uniquely stimulates and thermally stabilizes the ATP hydrolysis function of purified human CFTR...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27912062/atomic-structure-of-the-cystic-fibrosis-transmembrane-conductance-regulator
#3
Zhe Zhang, Jue Chen
The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel evolved from the ATP-binding cassette (ABC) transporter family. In this study, we determined the structure of zebrafish CFTR in the absence of ATP by electron cryo-microscopy to 3.7 Å resolution. Human and zebrafish CFTR share 55% sequence identity, and 42 of the 46 cystic-fibrosis-causing missense mutational sites are identical. In CFTR, we observe a large anion conduction pathway lined by numerous positively charged residues...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27906699/reversal-effects-of-local-anesthetics-on-p-glycoprotein-mediated-cancer-multidrug-resistance
#4
Yong Hu, Xiaobing Qin, Haixia Cao, Shaorong Yu, Jifeng Feng
The existence of multidrug resistance (MDR) is the main reason for failure in cancer chemotherapy. The main mechanism of MDR is the overexpression of P-glycoprotein (P-gp). P-gp, a 170 kDa transmembrane phosphorylated glycoprotein encoded by ABCB1 belonging to a member of the ATP-binding cassette (ABC) super-family of the membrane transporters, is also known as the MDR protein. Local anesthetics (LAs) are a major contributor to medical practice. As a cornerstone of analgesia, LAs provides myriad benefits...
November 30, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27903987/mapping-heterogeneity-in-patient-derived-melanoma-cultures-by-single-cell-rna-seq
#5
Tobias Gerber, Edith Willscher, Henry Loeffler-Wirth, Lydia Hopp, Dirk Schadendorf, Manfred Schartl, Ulf Anderegg, Gray Camp, Barbara Treutlein, Hans Binder, Manfred Kunz
Recent technological advances in single-cell genomics make it possible to analyze cellular heterogeneity of tumor samples. Here, we applied single-cell RNA-seq to measure the transcriptomes of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively. Analysis based on self-organizing maps identified sub-populations defined by multiple gene expression modules involved in proliferation, oxidative phosphorylation, pigmentation and cellular stroma...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901114/genome-wide-diversity-and-association-mapping-for-capsaicinoids-and-fruit-weight-in-capsicum-annuum-l
#6
Padma Nimmakayala, Venkata L Abburi, Thangasamy Saminathan, Suresh B Alaparthi, Aldo Almeida, Brittany Davenport, Marjan Nadimi, Joshua Davidson, Krittika Tonapi, Lav Yadav, Sridhar Malkaram, Gopinath Vajja, Gerald Hankins, Robert Harris, Minkyu Park, Doil Choi, John Stommel, Umesh K Reddy
Accumulated capsaicinoid content and increased fruit size are traits resulting from Capsicum annuum domestication. In this study, we used a diverse collection of C. annuum to generate 66,960 SNPs using genotyping by sequencing. The study identified 1189 haplotypes containing 3413 SNPs. Length of individual linkage disequilibrium (LD) blocks varied along chromosomes, with regions of high and low LD interspersed with an average LD of 139 kb. Principal component analysis (PCA), Bayesian model based population structure analysis and an Euclidean tree built based on identity by state (IBS) indices revealed that the clustering pattern of diverse accessions are in agreement with capsaicin content (CA) and fruit weight (FW) classifications indicating the importance of these traits in shaping modern pepper genome...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895130/metq-of-neisseria-gonorrhoeae-is-a-surface-expressed-antigen-that-elicits-bactericidal-and-functional-blocking-antibodies
#7
Evgeny A Semchenko, Christopher J Day, Kate L Seib
Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection (STI) gonorrhoea, is a growing public health threat for which a vaccine is urgently needed. We have characterized the functional role of the gonococcal MetQ protein, which is the methionine binding component of an ABC transporter system, and assessed its potential as a candidate antigen for inclusion in a gonococcal vaccine. MetQ is highly conserved in all strains investigated to date, it is localized on the bacterial surface, and it binds L-methionine with high affinity...
November 28, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27888075/the-domain-ii-loops-of-bacillus-thuringiensis-cry1aa-form-an-overlapping-interaction-site-for-two-bombyx-mori-larvae-functional-receptors-abc-transporter-c2-and-cadherin-like-receptor
#8
Satomi Adegawa, Yui Nakama, Haruka Endo, Naoki Shinkawa, Shingo Kikuta, Ryoichi Sato
Information about the receptor-interaction region of Cry toxins, insecticidal proteins produced by Bacillus thuringiensis, is needed to elucidate the mode of action of Cry toxins and improve their toxicity through protein engineering. We analyzed the interaction sites on Cry1Aa with ABC transporter C2 (ABCC2), one of the most important Cry1A toxin receptors. A competitive binding assay revealed that the Bombyx mori ABCC2 (BmABCC2) Cry1A binding site was the same as the BtR175 binding site, suggesting that the loop region of Cry1Aa domain II is a binding site...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27886333/association-between-the-polymorphisms-in-the-atp-binding-cassette-genes-abcb1-and-abcc2-and-the-risk-of-drug-resistant-epilepsy-in-a-chinese-han-population
#9
T Xue, Z N Lu
Epilepsy is a common disease of the nervous system; approximately 20-30% of all patients with epilepsy are reported resistant to antiepileptic drugs. ABCB1 and ABCC2 are members of ATP-binding cassette transporter (ABC) family that is involved in the excretion of antiepileptic drugs. In this case-control study, we have investigated the role of ABCB1 rs1045642 and rs2032582 and ABCC2 rs2273697 and rs717620 single nucleotide polymorphisms in antiepileptic drug-resistance in patients with epilepsy. A total of 254 patients with epilepsy (104 drug-resistant and 150 drug-responsive) were recruited from the People's Hospital of Wuhan University between March 2013 and April 2014...
November 25, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27878697/nf%C3%AE%C2%BAbp65-transcription-factor-modulates-resistance-to-doxorubicin-through-abc-transporters-in-breast-cancer
#10
Kobra Velaei, Nasser Samadi, Sina Soltani, Balal Barazvan, Jafar Soleimani Rad
BACKGROUND: Shedding light on chemoresistance biology of breast cancer could contribute to enhance the clinical outcome. Intrinsic or acquired resistance to chemotherapy is a major problem in breast cancer treatment. METHODS AND MATERIALS: The NFκB pathway by siRNAP65 and JSH-23 as a translocational inhibitor of NFκBP65 in the doxorubicin-resistant MCF-7 (MCF-7/Dox) and MCF-7 cells was blocked. Then, the ABC transporter expression and function were assessed by real-time qRT-PCR and flow cytometry, respectively...
November 23, 2016: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/27874224/multiple-transporters-are-involved-in-natamycin-efflux-in-streptomyces-chattanoogensis-l10
#11
Tan-Jun Wang, Yi-Ming Shan, Han Li, Wei-Wang Dou, Xin-Hang Jiang, Xu-Ming Mao, Shui-Ping Liu, Wen-Jun Guan, Yong-Quan Li
Antibiotic-producing microorganisms have evolved several self-resistance mechanisms to prevent auto-toxicity. Overexpression of specific transporters to improve the efflux of toxic antibiotics has been found one of the most important and intrinsic resistance strategies employed by many Streptomyces strains. In this work, two ATP-binding cassette (ABC) transporter-encoding genes located in the natamycin biosynthetic gene cluster, scnA and scnB, were identified as the primary exporter genes for natamycin efflux in Streptomyces chattanoogensis L10...
November 22, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27870912/atp-hydrolysis-induced-conformational-changes-in-the-vitamin-b12-transporter-btucd-revealed-by-md-simulations
#12
Chao Pan, Jingwei Weng, Wenning Wang
ATP binding cassette (ABC) transporters utilize the energy of ATP hydrolysis to uni-directionally transport substrates across cell membrane. ATP hydrolysis occurs at the nucleotide-binding domain (NBD) dimer interface of ABC transporters, whereas substrate translocation takes place at the translocation pathway between the transmembrane domains (TMDs), which is more than 30 angstroms away from the NBD dimer interface. This raises the question of how the hydrolysis energy released at NBDs is "transmitted" to trigger the conformational changes at TMDs...
2016: PloS One
https://www.readbyqxmd.com/read/27865021/ligand-binding-specificity-of-the-escherichia-coli-periplasmic-histidine-binding-protein-hisj
#13
Subrata Paul, Sambuddha Banerjee, Hans J Vogel
The HisJ protein from Escherichia coli and related Gram negative bacteria is the periplasmic component of a bacterial ATP-cassette (ABC) transporter system. Together these proteins form a transmembrane complex that can take up L-histidine from the environment and translocate it into the cytosol. We have studied the specificity of HisJ for binding L-His and many related naturally occurring compounds. Our data confirm that L-His is the preferred ligand, but that 1-methyl-L-His and 3-methyl-L-His can also bind, while the dipeptide carnosine binds weakly and D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind...
November 12, 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27859397/global-transcriptomic-response-of-anoxybacillus-sp-sk-3-4-to-aluminum-exposure
#14
Jia Chun Lim, Suganthi Thevarajoo, Chitra Selvaratnam, Kian Mau Goh, Mohd Shahir Shamsir, Zaharah Ibrahim, Chun Shiong Chong
Anoxybacillus sp. SK 3-4 is a Gram-positive, rod-shaped bacterium and a member of family Bacillaceae. We had previously reported that the strain is an aluminum resistant thermophilic bacterium. This is the first report to provide a detailed analysis of the global transcriptional response of Anoxybacillus when the cells were exposed to 600 mg L(-1) of aluminum. The transcriptome was sequenced using Illumina MiSeq sequencer. Total of 708 genes were differentially expressed (fold change >2.00) with 316 genes were up-regulated while 347 genes were down-regulated, in comparing to control with no aluminum added in the culture...
November 17, 2016: Journal of Basic Microbiology
https://www.readbyqxmd.com/read/27856528/in-vivo-hepatic-enhancer-elements-in-the-human-abcg2-locus
#15
Rachel J Eclov, Mee J Kim, Robin P Smith, Xiaomin Liang, Nadav Ahituv, Deanna L Kroetz
ABCG2 encodes the mitoxantrone resistance protein (MXR, BCRP), an ATP-binding cassette (ABC) efflux membrane transporter. Computational analysis of the ~300 kb region of DNA surrounding ABCG2 (chr4:88911376-89220011, hg19) identified 30 regions with potential cis-regulatory capabilities. These putative regulatory regions were tested for their enhancer and suppressor activity in a human liver cell line using luciferase reporter assays. The in vitro enhancer and suppressor assays identified four regions that decreased gene expression and five regions that increased expression >1...
November 17, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27856319/elucidation-of-biocontrol-mechanisms-of-trichoderma-harzianum-against-different-plant-fungal-pathogens-universal-yet-host-specific-response
#16
Vivek Sharma, Richa Salwan, Prem N Sharma, S S Kanwar
In the present study, different transcripts of Trichoderma harzianum ThHP-3 were evaluated for their response against four fungal pathogens Fusarium oxysporum, Colletotrichum capsici, Colletotrichum truncatum and Gloesercospora sorghi using RT-qPCR. The time course study of T. harzianum transcripts related to signal transduction, lytic enzymes, secondary metabolites and various transporters revealed variation in expression against four fungal pathogens. In a broader term, the transcripts were upregulated at various time intervals but the optimum expression of cyp3, abc, nrp, tga1, pmk, ech42 and glh20 varied with respect to host fungi...
November 14, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27855620/mrp1-dependent-collateral-sensitivity-of-multidrug-resistant-cancer-cells-identifying-selective-modulators-inducing-cellular-glutathione-depletion
#17
Doriane Lorendeau, Lauriane Dury, Rachad Nasr, Ahcène Boumendjel, Elisabetta Teodori, Michael Gütschow, Pierre Falson, Attilio Di Pietro, Hélène Baubichon-Cortay
Cancer cells are permanently being selected for survival and proliferation. During this process, tumor cells often co-opt basic physiological mechanisms to protect themselves from toxic chemotherapy. One of these mechanisms is the overexpression of ATP-binding cassette (ABC) drug efflux pumps leading to multidrug resistance (MDR) of cancer cells through an increase of drug efflux. In the past 20 years, many efforts were done to circumvent MDR through the inhibition of ABC transporters. A number of inhibitors of these transporters were found but are rarely specific or rationally developed...
November 18, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27852125/standardized-extract-from-caesalpinia-spinosa-is-cytotoxic-over-cancer-stem-cells-and-enhance-anticancer-activity-of-doxorubicin
#18
Tito A Sandoval, Claudia P Urueña, Mónica Llano, Alejandra Gómez-Cadena, John F Hernández, Luis Gonzalo Sequeda, Alix E Loaiza, Alfonso Barreto, Shaoping Li, Susana Fiorentino
Cancer stem cells (CSC) are the primary cell type responsible for metastasis and relapse. ABC-transporters are integral membrane proteins involved in the translocation of substrates across membranes protecting CSC from chemotherapeutic agents. A plant extract derived from C. spinosa (P2Et) previously investigated for its antitumor activity has been shown to reduce lung and spleen metastasis in mice that have been transplanted with breast cancer cells, suggesting that P2Et has a significant activity against cancer stem cells (CSC)...
November 16, 2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27852006/a-combination-of-photodynamic-therapy-and-chemotherapy-displays-a-differential-cytotoxic-effect-on-human-metastatic-melanoma-cells
#19
Fa Nsole Biteghe, L M Davids
BACKGROUND: Cutaneous melanoma represents the most lethal form of skin cancer and remains refractory to current therapies. Failure of treatment has been attributed to the over-expression of ABC transporters which efflux the drugs, below their cytotoxic threshold within cells. Therefore, this study set to investigate; the efficacy of a combinatorial approach comprising chemotherapy (Dacarbazine) and photodynamic therapy (PDT) to overcome resistance in pigmented and unpigmented metastatic melanoma and potentially identify resistant mechanisms...
November 8, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27851764/kinetic-modeling-of-abcg2-transporter-heterogeneity-a-quantitative-single-cell-analysis-of-the-side-population-assay
#20
Adam F Prasanphanich, Douglas E White, Margaret A Gran, Melissa L Kemp
The side population (SP) assay, a technique used in cancer and stem cell research, assesses the activity of ABC transporters on Hoechst staining in the presence and absence of transporter inhibition, identifying SP and non-SP cell (NSP) subpopulations by differential staining intensity. The interpretation of the assay is complicated because the transporter-mediated mechanisms fail to account for cell-to-cell variability within a population or adequately control the direct role of transporter activity on staining intensity...
November 2016: PLoS Computational Biology
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