KAMISAKO, T. and OGAWA, H. (2005), Alteration of the expression of adenosine triphosphate-binding cassette transporters associated with bile acid and cholesterol transport in the rat liver and intestine during cholestasis. Journal of Gastroenterology and Hepatology, 20: 1429-1434. doi: 10.1111/j.1440-1746.2005.03950.x ...

Title: Structure and Function of the Human Breast Cancer Resistance Protein (BCRP/ABCG2). VOLUME: 11 ISSUE: 7. Author(s):Zhanglin Ni, Zsolt Bikadi, Mark F. Rosenberg and Qingcheng Mao. Affiliation:Department of Pharmaceutics,School of Pharmacy, University of Washington, Health Science Building H272, 1959 NE Pacific Street , Seattle, Washington 98195-7610, USA.. Keywords:Breast cancer resistance protein, BCRP, ATP-binding cassette transporter, ABCG2, multidrug resistance, drug disposition, homology model, mutation analysis, BCRP/ABCG2, mitoxantrone-resistant human cancer cell lines, MXR, human placenta, ABCP, nucleotide binding domains, membrane spanning domains, MSDs, affinity constants, SAR, QSAR, flavonoids, tamoxifen analogues, cyclindependent kinase inhibitors, tariquidar analogues, FTC analogues, 2D-QSAR, CoMFA, CoMSIA, 3D-QSAR, MIFs, HEK cells, Pichia pastoris, Lactococcus lactis, fluorescence resonance energy transfer v, MODELLER. Abstract: The human breast cancer resistance protein ...

ABCC4 (Myc-DDK-tagged)-Human ATP-binding cassette, sub-family C (CFTR/MRP), member 4 (ABCC4), transcript variant 2 - 10 µg - OriGene - cdna clones

TY - JOUR. T1 - A novel mutation in the ABCR gene in four patients with autosomal recessive Stargardt disease. AU - Zhang, Kang. AU - Garibaldi, Daniel C.. AU - Kniazeva, Marina. AU - Albini, Thomas. AU - Chiang, Michael F.. AU - Kerrigan, Michelle. AU - Sunness, Janet S.. AU - Han, Min. AU - Allikmets, Rando. PY - 1999/12/1. Y1 - 1999/12/1. N2 - PURPOSE: To identify additional mutations in the ABCR gene and describe the clinical features of four affected siblings with autosomal recessive Stargardt disease. METHODS: A cohort of eight siblings was identified for study. Four of these individuals were diagnosed with Stargardt disease based on clinical evaluation and fluorescein angiography. Blood samples were obtained from seven of eight siblings, including all those affected. All 50 exons of the ABCR gene were analyzed by single-stranded confirmation polymorphism analysis, followed by direct sequencing of observed variants, to identify mutations in the ABCR gene. RESULTS: We identified a ...

Overexpression of adenosine triphosphate-binding cassette (ABC) transport proteins is emerging seeing that a crucial contributor to anticancer medication level of resistance. assays. eIF4G mRNA degradation was accelerated in cells transfected with miR-503 mimics. Furthermore, it had been demonstrated that eIF4G and ABC translation protein were downregulated in MCF-7/ADR cells after transfection with miR-503 significantly. It was discovered that miR-503 mimics could sensitize the cells to treatment with ADM, TAX and TAM. These findings confirmed for the very first time that eIF4G acted as an integral element in MCF-7/ADR cells, and Riociguat could end up being a competent agent for preventing and reversing multi-drug resistance in breast malignancy. (11) determinded that cisplatin-resistance cells upregulated MRP1 when compared with sensitive MCF-7 cells. The eukaryotic initiation factor (eIF) 4F complex consists of three proteins: cap-binding protein eIF4E, scaffolding protein eIF4G and ...

Title: Interaction of Probenecid with the Breast Cancer Resistance Protein Transporter (BCRP/ABCG2). VOLUME: 3 ISSUE: 4. Author(s):G. Merino, R. Real, A. J. Molina, M. M. Pulido, J. G. Prieto and A. I. Alvarez. Affiliation:University of León,Department of Physiology, Faculty of Veterinary Medicine, Campus deVegazana 24071 León, Spain.. Keywords:Probenecid, Breast Cancer Resistance Protein, P-glycoprotein, transport, inhibition. Abstract: Probenecid is used as a uricosuric agent in the treatment of chronic gout and as an adjunct to enhance antibiotic levels in the blood. For research purposes, it is used as a prototypic inhibitor of organic anion transporters and MRPs, including MPR2. The purpose of this research is to study the interaction of probenecid with two other important transporters of the ATP-binding cassette family, Breast Cancer Resistance Protein (BCRP) and P-glycoprotein. These drug efflux transporters are present in the intestine, liver and other organs, and they affect the ...

The transport of molecules across lipid membranes is an essential function of all living organisms. One of the families of genes that have evolved to carry out this function is that which encodes the ATP-binding cassette proteins. These molecules use active transport to pump specific molecules acros …

During the past years, we and others discovered a series of human ATP-binding cassette (ABC) transporters, now referred to as ABC A-subfamily transporters. Recently, a novel testis-specific ABC A transporter, Abca17, has been cloned in rodent. In this study, we report the identification and characterization of the human ortholog of rodent Abca17. The novel human ABC A-transporter gene on chromosome 16p13.3 is ubiquitously expressed with highest expression in glandular tissues and the heart. The new ABC transporter gene exhibits striking nucleotide sequence homology with the recently cloned mouse (58%) and rat Abca17 (51%), respectively, and is located in the syntenic region of mouse Abca17 indicating that it represents the human ortholog of rodent Abca17. However, unlike in the mouse, the full-length ABCA17 transcript (4.3 kb) contains numerous mutations that preclude its translation into a bona fide ABC transporter protein strongly suggesting that the human ABCA17 gene is a transcribed pseudogene

[51 Pages Report] Check for Discount on ATP Binding Cassette Sub Family A Member 1 (ATP Binding Cassette Transporter 1 or ABC 1 or ATP Binding Cassette 1 or Cholesterol Efflux Regulatory Protein or ABCA1) - Pipeline Review, H1 2016 report by Global Markets Direct. Global Markets Directs, ATP Binding Cassette Sub...

TY - JOUR. T1 - Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. AU - Noguchi, Kohji. AU - Katayama, Kazuhiro. AU - Mitsuhashi, Junko. AU - Sugimoto, Yoshikazu. N1 - Funding Information: We apologize that, due to space limitations, we could not cite the excellent work of many investigators. This work was supported by a grant-in-aid for Cancer Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.. PY - 2009/1/31. Y1 - 2009/1/31. N2 - The breast cancer resistance protein, BCRP/ABCG2, is a half-molecule ATP-binding cassette transporter that facilitates the efflux of various anticancer agents from the cell, including 7-ethyl-10-hydroxycamptothecin, topotecan and mitoxantrone. The expression of BCRP can thus confer a multidrug resistance phenotype in cancer cells, and its transporter activity is involved in the in vivo efficacy of chemotherapeutic agents. Thus, the elucidation of the substrate preferences and structural relationships ...

ATP-binding cassette transporters (ABC transporters) are members of a transport system superfamily that is one of the largest and is possibly one of the oldest families with representatives in all extant phyla from prokaryotes to humans. ABC transporters often consist of multiple subunits, one or two of which are transmembrane proteins and one or two of which are membrane-associated ATPases. The ATPase subunits utilize the energy of adenosine triphosphate (ATP) binding and hydrolysis to energize the translocation of various substrates across membranes, either for uptake or for export of the substrate. Most but not all uptake systems also have an extracytoplasmic receptor, a solute binding protein. Some homologous ATPases function in non-transport-related processes such as translation of RNA and DNA repair. ABC transporters are considered to be with the ABC superfamily based on the sequence and organization of their ATP-binding cassette (ABC) domains, even though the integral membrane proteins ...

We characterized a new human ATP-binding cassette (ABC) transporter gene that is highly expressed in the placenta. The gene, ABCP, produces two transcripts that differ at the 5′ end and encode the same 655-amino acid protein. The predicted protein is closely related to the Drosophila white and yeast ADP1 genes and is a member of a subfamily that includes several multidrug resistance transporters. ABCP, white, and ADP1 all have a single ATP-binding domain at the NH2 terminus and a single COOH-terminal set of transmembrane segments. ABCP maps to human chromosome 4q22, between the markers D4S2462 and D4S1557, and the murine gene (Abcp) is located on chromosome 6 28-29 cM from the centromere. ABCP defines a new syntenic segment between human chromosome 4 and mouse chromosome 6. The abundant expression of this gene in the placenta suggests that the protein product has an important role in transport of specific molecule(s) into or out of this tissue.. ...

With the well-established link between serum cholesterol levels and cardiovascular disease and the availability of effective cholesterol-lowering drugs, cholesterol screening has rapidly become a routine part of health care. Yet, much remains to be learned about how cholesterol levels are regulated at the cellular level (see the Perspective by Brown et al.). Now, Najafi-Shoushtari et al. (p. 1566, published online 13 May) and Rayner et al. (p. 1570, published online 13 May) have discovered a new molecular player in cholesterol control-a small noncoding RNA that, intriguingly, is embedded within the genes coding for sterol regulatory element-binding proteins (SREBPs), transcription factors already known to regulate cholesterol levels. This microRNA, called miR-33, represses expression of the adenosine triphosphate-binding cassette transporter A1, a protein that regulates synthesis of high-density lipoprotein (HDL, or good cholesterol) and that helps to remove bad cholesterol from the blood. ...

1. Higgins CF. ABC transporters: from microorganisms to man. Annu Rev Cell Biol. 1992;8: 67-113. doi: 10.1146/annurev.cb.08.110192.000435 1282354. 2. Rees DC, Johnson E, Lewinson O. ABC transporters: the power to change. Nat Rev Mol Cell Biol. 2009;10: 218-227. doi: 10.1038/nrm2646 19234479. 3. Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001;11: 1156-1166. doi: 10.1101/gr.184901 11435397. 4. Klein I, Sarkadi B, Varadi A. An inventory of the human ABC proteins. Biochim Biophys Acta-Biomembr. 1999;1461: 237-262. doi: 10.1016/S0005-2736(99)00161-3. 5. Seeger MA, van Veen HW. Molecular basis of multidrug transport by ABC transporters. Biochim Biophys Acta BBA-Proteins Proteomics. 2009;1794: 725-737. doi: 10.1016/j.bbapap.2008.12.004 19135557. 6. Holland IB, A. Blight M. ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules in organisms from bacteria to humans. J Mol Biol. 1999;293: 381-399. ...

With the well-established link between serum cholesterol levels and cardiovascular disease and the availability of effective cholesterol-lowering drugs, cholesterol screening has rapidly become a routine part of health care. Yet, much remains to be learned about how cholesterol levels are regulated at the cellular level (see the Perspective by Brown et al.). Now, Najafi-Shoushtari et al. and Rayner et al. have discovered a new molecular player in cholesterol control-a small noncoding RNA that, intriguingly, is embedded within the genes coding for sterol regulatory element-binding proteins (SREBPs), transcription factors already known to regulate cholesterol levels. This microRNA, called miR-33, represses expression of the adenosine triphosphate-binding cassette transporter A1, a protein that regulates synthesis of high-density lipoprotein (HDL, or good cholesterol) and that helps to remove bad cholesterol from the blood. Reducing the levels of miR-33 in mice boosted serum HDL levels, ...

Membrane transport proteins are known to influence the absorption, distribution, metabolism, excretion and toxicity (ADMET) of drugs. At the onset of this thesis work, only a few structure-activity models, in general describing P-glycoprotein (Pgp/ABCB1) interactions, were developed using small datasets with little structural diversity. In this thesis, drug-transport protein interactions were explored using large, diverse datasets representing the chemical space of orally administered registered drugs. Focus was set on the ATP-binding cassette (ABC) transport proteins expressed in the canalicular membrane of human hepatocytes.. The inhibition of the ABC transport proteins multidrug-resistance associated protein 2 (MRP2/ABCC2) and bile salt export pump (BSEP/ABCB11) was experimentally investigated using membrane vesicles from cells overexpressing the investigated proteins and sandwich cultured human hepatocytes (SCHH). Several previously unknown inhibitors were identified for both of the proteins ...

TY - JOUR. T1 - ATP-binding cassette transporter A1 (ABCA1) R219K (G1051A, rs2230806) polymorphism and serum high-density lipoprotein cholesterol levels in a large Japanese population. T2 - Cross-sectional data from the Daiko study. AU - Mokuno, Junichiro. AU - Hishida, Asahi. AU - Morita, Emi. AU - Sasakabe, Tae. AU - Hattori, Yuta. AU - Suma, Shino. AU - Okada, Rieko. AU - Kawai, Sayo. AU - Naito, Mariko. AU - Wakai, Kenji. PY - 2015/4/11. Y1 - 2015/4/11. N2 - Among polymorphisms in ATP-binding cassette transporter Al (ABCA1) gene, the available evidence demonstrates that the ABCA1 R219K polymorphism (G1051A, rs2230806) K allele is associated with a higher high-density lipoprotein cholesterol (HDL- C) level and may play a protective role against coronary artery disease (CAD) risk in Asians and Caucasians. The findings from many underpowered studies from Asian countries (n=71-597), however, still remain inconsistent. The objective of this study was to overcome the limitations of previous ...

K11085 msbA; ATP-binding cassette, subfamily B, bacterial MsbA [EC:3.6.3.-] K11085 msbA; ATP-binding cassette, subfamily B, bacterial MsbA [EC:3.6.3.-] K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06147 ABCB-BAC; ATP-binding cassette, subfamily B, bacterial K06160 pvdE; putative pyoverdin transport system ATP-binding/permease protein K15738 uup; ABC transport system ATP-binding/permease protein K21397 K21397; ABC transport system ATP-binding/permease protein K21397 K21397; ABC transport system ATP-binding/permease protein K23163 sbp; sulfate/thiosulfate transport system substrate-binding protein K02046 cysU; ...

Introduction Recently, the ATP-binding cassette transporter BCRP1/ABCG2 has been shown to regulate the function and survival of side population cells, which have been identified in various organs including heart and have stem cell properties. In addition, previous studies have revealed that BCRP1/ABCG2 is also expressed in endothelial cells of capillaries and arterioles in heart. This study was performed to clarify the role of BCRP1/ABCG2 in cardiac repair after myocardial infarction (MI).. Methods and Results MI was induced in 8- to 12-week-old wild-type (WT) mice (n=51) and Bcrp1/Abcg2 knock-out (KO) mice (n=60) by ligating the left anterior descending artery. At 28 days after MI, the survival rate was significantly lower in KO mice than in WT mice (28.3% versus 74.5%, p=0.0001). The main cause of death in KO mice was cardiac rupture (CR) (67.4%), whereas CR was observed in only 30.8% among WT mice (p=0.019). Echocardiography showed that ventricular remodeling was more deteriorated in KO mice ...

ABCF3 - ABCF3 (Myc-DDK-tagged)-Human ATP-binding cassette, sub-family F (GCN20), member 3 (ABCF3) available for purchase from OriGene - Your Gene Company.

Purpose : The retina specific ATP binding cassette transporter A4 (ABCA4) is necessary for the clearance of all-trans-retinal from photoreceptor cells. Loss of this crucial function results in the accumulation of toxic bisretinoids, primarily N-retinylidene-N-retinylethanolamine (A2E). This ultimately leads to the Stargardt phenotype of increased autofluorescence and progressive RPE and photoreceptor cell loss. Adeno-associated virus (AAV) vectors have proven their utility for efficient gene transfer in the retina to a variety of cell types. However, the ABCA4 coding sequence (cds) of 6.8kb exceeds the payload capacity of a single AAV capsid of 4.8kb by far. AAV dual vectors have been shown to overcome this size restriction by splitting the cds between two vectors and packaging them in separate capsids. After co-infection of a cell the two vectored cDNAs recombine to reconstitute the full length cds. Here we present recent data on the effect of AAV dual vector mediated ABCA4 gene replacement ...

Division of Molecular Biotherapy [Y. I., M. N., K. K., S. T., E. I., Y. S.] and Division of Experimental Chemotherapy [T. T.], Cancer Chemotherapy Center, and Department of Molecular Diagnosis [Y. M.], Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 170-8455, and Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032 [T. T.], ...

Synthesis of carbon-11-labeled tariquidar derivatives as new PET agents for imaging of breast cancer resistance protein (ABCG2). Appl Radiat Isot. 2010 Jun; 68(6):1098-103 ...

Cell Biol Int. 2021 Mar 24. doi: 10.1002/cbin.11598. Online ahead of print.. ABSTRACT. Overexpression of breast cancer resistance protein (BCRP) plays a crucial role in the acquired multidrug resistance (MDR) in breast cancer. The elucidation of molecular events that confer BCRP-mediated MDR is of major therapeutic importance in breast cancer. Epithelial cell adhesion molecule (EpCAM) has been implicated in tumor progression and drug resistance in various types of cancers, including breast cancer. However, the role of EpCAM in BCRP-mediated MDR in breast cancer remains unknown. In the present study, we revealed that EpCAM expression was upregulated in BCRP-overexpressing breast cancer MCF-7/MX cells, and EpCAM knockdown using siRNA reduced BCRP expression and increased the sensitivity of MCF-7/MX cells to mitoxantrone (MX). Epithelial-mesenchymal transition (EMT) promoted BCRP-mediated MDR in breast cancer cells, and EpCAM knockdown partially suppressed EMT progression in MCF-7/MX cells. In ...

hypothetical protein, ABCB1LB, ATP-binding cassette, sub-family B (MDR/TAP), member 1-like B, A306_07528, ABC16, ABC member 16, MDR/TAP subfamily, AS27_06659, AS28_00614, ATP-binding cassette protein B11, ATP-binding cassette, sub-family B (MDR/TAP), member 11, ATP-binding cassette, subfamily B (MDR/TAP), member 11, ATP-binding cassette, sub-family B (MDR/TAP), member 11-like protein, ATP-binding cassette sub-family B member 11, ATP-binding cassette, sub-family B, member 11, bile salt export pump, BRIC2, BSEP, BSEP/SPGP, CB1_000638007, D623_10034923, GW7_06212, H920_16172, I79_001236, Lith1, liver bile salt export pump, M91_01875, M959_07155, MDA_GLEAN10024246, Multidrug resistance protein 1, N301_03105, N302_06788, N303_07198, N305_06591, N306_04080, N307_07545, N308_11810, N309_07944, N312_11735, N321_13718, N327_01303, N328_07355, N329_09470, N331_01374, N332_02914, N333_01536, N334_13094, N336_04014, N340_01262, N341_10800, PAL_GLEAN10025937, PFIC2, PFIC-2, PGY4, progressive familial ...

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specificalPrinciple of the Assay: The test principle applied in this kit is Sandwich enzyme immunoassay. The microtiter plate provided in this kit has been pre-coated with an antibody specific to ATP Binding Cassette Transporter C3 (ABCC3). Standards or samples are then added to the appropriate microtiter plate wells with a biotin-conjugated antibody specific to ATP Binding Cassette Transporter C3 (ABCC3). Next, Avidin conjugated to Horseradish Peroxidase (HRP) is added to each microplate well and incubated. After TMB substrate solution is added, only those wells that contain ATP Binding Cassette Transporter C3 (ABCC3), biotin-conjugated antibody and enzyme-conjugated Avidin will exhibit a change in color. The enzyme-substrate reaction is terminated by the addition of sulphuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450nm ± 10nm. The concentration of ATP Binding Cassette Transporter C3 (ABCC3) in the samples is then determined by comparing the ...

The ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of cellular unesterified cholesterol and phospholipid to lipid-poor apolipoprotein A-I. Chymase, a protease secreted by mast cells, selectively cleaves pre-β-migrating particles from high density lipoprotein (HDL)3 and reduces the efflux of cholesterol from macrophages. To evaluate whether this effect is the result of reduction of ABCA1-dependent or -independent pathways of cholesterol efflux, in this study we examined the efflux of cholesterol to preparations of chymase-treated HDL3 in two types of cell: 1) in J774 murine macrophages endogenously expressing low levels of scavenger receptor class B, type I (SR-BI), and high levels of ABCA1 upon treatment with cAMP; and 2) in Fu5AH rat hepatoma cells endogenously expressing high levels of the SR-BI and low levels of ABCA1. Treatment of HDL3 with the human chymase resulted in rapid depletion of pre-β-HDL and a concomitant decrease in the efflux of cholesterol and phospholipid ...

ABCA12 - ABCA12 (Myc-DDK-tagged)-Human ATP-binding cassette, sub-family A (ABC1), member 12 (ABCA12), transcript variant 2 available for purchase from OriGene - Your Gene Company.

Cholesterol is an essential molecule that mediates a myriad of critical cellular processes, such as signal transduction in eukaryotes, membrane fluidity, and steroidogenesis. As such it is not surprising that cholesterol homeostasis is tightly regulated, striking a precise balance between endogenous synthesis and regulated uptake/efflux to and from extracellular acceptors. In mammalian cells, sterol efflux is a key component of the homeostatic equation and is mediated by members of the ATP binding cassette (ABC) transporter superfamily. ATP-binding cassette (ABC) transporters represent a group of evolutionarily highly conserved cellular transmembrane proteins that mediate the ATP-dependent translocation of substrates across membranes. Members of this superfamily, ABCA1 and ABCG1, are key components of the reverse cholesterol transport pathway. ABCG1 acts in concert with ABCA1 to maximize the removal of excess cholesterol from cells by promoting cholesterol efflux onto mature and nascent HDL particles

S. griseus mutant NP4, which was isolated by UV mutagenesis, showed a bald and wrinkled colony morphology because of ectopic septation in substrate hyphae and subsequent spore formation. The ectopic spores were the same as aerial spores in size, thickness of the spore wall, and shape, as determined by transmission and scanning electron microscopy, and in heat and lysozyme susceptibility. Mutant NP4 also formed abundant spores in liquid medium, whereas the parental strain IFO13350 rarely forms submerged spores under these conditions. The wall of the ectopic spores is supposed to be thicker than those of the submerged spores formed by several Streptomyces spp., including S. griseus B-2682 (32), under specific conditions, because the spores of NP4 were resistant to lysozyme. We therefore assume that both on solid and in liquid medium, mutant NP4 forms two separate cross walls in the vegetative hyphae and matures each compartment into a spore indistinguishable from aerial spores in many aspects, as ...

Active drug efflux by the adenosine triphosphate-binding cassette (ABC) transporter ABCG2 is one of the common mechanisms causing multiple drug resistance in various human cancers. In the intrinsic drug resistance of hepatocellular carcinoma (HCC), the role of ABCG2 is closely associated with side population (SP), a minor subset of cancer stem-like cells with unique capacity to extrude lipophilic dye Hoechst 33342 and many chemotherapeutic agents. In this study, we showed that ABCG2 was intrinsically expressed in a subgroup of HCC tissues and its expression pattern significantly influenced the levels of drug efflux from HCC cell lines. In MHCC-97L HCC cell line with intrinsic ABCG2 expression, we confirmed the importance of SP cells to the drug efflux-related chemotherapy resistance and found that the SP analysis provided an efficient method to evaluate the functional activity of ABCG2 transporter. In this cell line, we discovered that the SP proportion was modulated by the treatments of Akt ...

ATP binding cassette (ABC) transporters mediate vital transport processes in every living cell. ATP hydrolysis, which fuels transport, displays positive cooperativity in numerous ABC transporters. In particular, heterodimeric ABC exporters exhibit pronounced allosteric coupling between a catalytically impaired degenerate site, where nucleotides bind tightly, and a consensus site, at which ATP is hydrolyzed in every transport cycle. Whereas the functional phenomenon of cooperativity is well described, its structural basis remains poorly understood. Here, we present the apo structure of the heterodimeric ABC exporter TM287/288 and compare it to the previously solved structure with adenosine 5-(β,γ-imido)triphosphate (AMP-PNP) bound at the degenerate site. In contrast to other ABC exporter structures, the nucleotide binding domains (NBDs) of TM287/288 remain in molecular contact even in the absence of nucleotides, and the arrangement of the transmembrane domains (TMDs) is not influenced by ...

Mouse Monoclonal Anti-ABCD3 Antibody against Human ATP-binding cassette, sub-family D (ALD), member 3. Validated for Immunofluorescence and Immunohistochemistry

Our previous work shows that the stem cell factor SALL4 plays a central role in embryonic and leukemic stem cells. In this study, we report that SALL4 expression was higher in drug resistant primary acute myeloid leukemic patients than those from drug-responsive cases. In addition, while overexpression of SALL4 led to drug resistance in cell lines, cells with decreased SALL4 expression were more sensitive to drug treatments than the parental cells. This led to our investigation of the implication of SALL4 in drug resistance and its role in side population (SP) cancer stem cells. SALL4 expression was higher in SP cells compared to non-SP cells by 2-4 fold in various malignant hematopoietic cell lines. Knocking down of SALL4 in isolated SP cells resulted in a reduction of SP cells, indicating that SALL4 is required for their self-renewal. The SP phenotype is known to be mediated by members of the ATP-binding cassette (ABC) drug transport protein family, such as ABCG2 and ABCA3. Using ...

The ATP-sensitive K+ channel (KATP channel) couples glucose metabolism to insulin secretion in pancreatic beta-cells. It is comprised of sulfonylurea receptor (SUR)-1 and Kir6.2 proteins. Binding of Mg nucleotides to the nucleotide-binding domains (NBDs) of SUR1 stimulates channel opening and leads to membrane hyperpolarization and inhibition of insulin secretion. To elucidate the structural basis of this regulation, we constructed a molecular model of the NBDs of SUR1, based on the crystal structures of mammalian proteins that belong to the same family of ATP-binding cassette transporter proteins. This model is a dimer in which there are two nucleotide-binding sites, each of which contains residues from NBD1 as well as from NBD2. It makes the novel prediction that residue D860 in NBD1 helps coordinate Mg nucleotides at site 2. We tested this prediction experimentally and found that, unlike wild-type channels, channels containing the SUR1-D860A mutation were not activated by MgADP in either the presence

Transporter associated with antigen processing (TAP) is a member of the ATP-binding-cassette transporter family. It delivers cytosolic peptides into the endoplasmic reticulum (ER), where they bind to nascent MHC class I molecules. The TAP structure is formed of two proteins: TAP-1 and TAP-2, which have one hydrophobic region and one ATP-binding region each. They assemble into a heterodimer, which results in a four-domain transporter. The TAP transporter is found in the ER lumen associated with the peptide-loading complex (PLC). This complex of β2 microglobulin, calreticulin, ERp57, TAP, tapasin, and MHC class I acts to keep hold of MHC molecules until they have been fully loaded with peptides. TAP-mediated peptide transport is a multistep process. The peptide-binding pocket is formed by TAP-1 and TAP-2. Association with TAP is an ATP-independent event, in a fast bimolecular association step, peptide binds to TAP, followed by a slow isomerisation of the TAP complex. It is suggested that the ...

d-Methionine is an effective methionine source for Escherichia coli (5, 11, 14). The transport system reported to take up d-methionine in E. coli is encoded by the metD locus (11, 12). The system was found to be energized by ATP and regulated by the level of the internal methionine pool (10, 11, 13). The metD locus was mapped between the fhuA (previously called tonA) and the proA loci (12). The specific genes involved in d-methionine transport have not yet been reported.. We have identified the abc-yaeE-yaeC gene cluster (now renamed metNIQ genes) as a likely candidate for the metD locus in the fhuA-proA region. The abc gene was previously found in a search for ABC transporter ATP-binding domains (1). The PROSITE program (6) indicated that the Abc protein harbors an ATP- and GTP-binding site motif A (P-loop) (24) and an ABC transporter family signature (4). Gene yaeE encodes a putative membrane protein with a high sequence similarity to several bacterial amino acid transporters and contains a ...

Human Transporter Database: Comprehensive Knowledge and Discovery Tools in the Human Transporter Genes. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.

The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...

TY - JOUR. T1 - Drug efflux by breast cancer resistance protein is a mechanism of resistance to the benzimidazole insulin-like growth factor receptor/insulin receptor inhibitor, BMS-536924. AU - Hou, Xiaonan. AU - Huang, Fei. AU - Carboni, Joan M.. AU - Flatten, Karen. AU - Asmann, Yan. AU - Ten Eyck, Cynthia. AU - Nakanishi, Takeo. AU - Tibodeau, Jennifer D.. AU - Ross, Douglas D.. AU - Gottardis, Marco M.. AU - Erlichman, Charles. AU - Kaufmann, Scott H. AU - Haluska, Paul. PY - 2011/1. Y1 - 2011/1. N2 - Preclinical investigations have identified insulin-like growth factor (IGF) signaling as a key mechanism for cancer growth and resistance to clinically useful therapies in multiple tumor types including breast cancer. Thus, agents targeting and blocking IGF signaling have promise in the treatment of solid tumors. To identify possible mechanisms of resistance to blocking the IGF pathway, we generated a cell line that was resistant to the IGF-1R/InsR benzimidazole inhibitors, BMS-554417 and ...

GF120918 has a high inhibitory effect on P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). We developed [11C]GF120918 as a positron emissi

Active drug efflux transporters of the ATP binding cassette (ABC)-containing family of proteins have a major impact on the pharmacological behavior of most of the drugs in use today. Pharmacological properties affected by ABC transporters include the oral bioavailability, hepatobiliary, direct intes …

Background: Development of a multidrug resistance (MDR) phenotype to chemotherapy remains a major barrier in the treatment of cancer. Gankyrin (p28, p28GANK or PSMD10) is an oncoprotein overexpressed in different carcinoma cell lines. The aim of this study was to compare Gankyrin expression level in MDR cells (MCF-7/ADR and MCF-7/ MX) and non-MDR counterparts (MCF-7). Methods: Gankyrin, MDR1 (also known as ABCB1; the ATP-binding cassette sub-family B member 1) and ABCG2 (also known as BCRP; the human breast cancer resistance protein) mRNA levels were analyzed by real-time RT-PCR. Western blot analysis was used to detect the protein expression levels of Gankyrin. Results: The PCR results showed that the expression of Gankyrin was significantly lower in the ABCG2 overexpressing cell line MCF-7/MX than in non-resistanct MCF-7 cells. In contrast, there were no significant differences in mRNA expression of Gankyrin in the MDR1 overexpressing cell line MCF-7/ADR in comparison with MCF-7 cells. Similarly,

OR10G8 (olfactory receptor family 10 subfamily G member 8), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.

1. Jacquemin E. Progres-sive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol 2012; 36 (Suppl 1): S26- S35. doi: 10.1016/ S2210-7401(12)70018-9. 2. Strautnieks SS, Bull LN, Knisely AS et al. A gene encod-ing a liver-specific ABC transporter is mutated in progres-sive familial intrahepatic cholestasis. Nat Genet 1998; 20(3): 233- 238. 3. Jansen PL, Mül-ler M. The molecular genetics of familial intrahepatic cholestasis. Gut 2000; 47(1): 1- 5. 4. Gerloff T, Stieger B, Hagenbuch B et al. The sister of P-glycoprotein represents thecanalicular bile salt export pump of mam-malian liver. J Biol Chem 1998; 273(16): 10046- 10050. 5. Davis RA, Miyake JH, Hui TY et al. Regulation of cholesterol-7alpha-hydroxylase: BAREly mis-s-ing SHP. J Lipid Res 2002; 43(4): 533- 543. 6. Thompson R, Strautnieks SS. BSEP: function and role in progres-sive familial intrahepatic cholestasis. Semin Liver Dis 2001; 21(4): 545- 550. 7. Kaliciński PJ, Ismail H, Jankowska I et al. Surgical treatment of ...

TY - JOUR. T1 - Mutations in the canalicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome. AU - Wada, Morimasa. AU - Toh, Satoshi. AU - Taniguchi, Ken. AU - Nakamura, Takanori. AU - Uchiumi, Takeshi. AU - Kohno, Kimitoshi. AU - Yoshida, Ichiro. AU - Kimura, Akihiko. AU - Sakisaka, Shotaro. AU - Adachi, Yukihiko. AU - Kuwano, Michihiko. PY - 1998/2. Y1 - 1998/2. N2 - Members of the ATP-binding cassette (ABC) transporter superfamily are mutated to cause diseases that include cystic fibrosis, hyperinsulinemia, adrenoleukodystrophy, Stargardt disease and multidrug resistance. We recently isolated a novel human member of ABC transporter superfamily as the candidate transporter for the glucuronide and glutathione-conjugated antitumor agents, and found it highly homologous to the rat cmoat gene. Consistent with recent findings of defects in the homologous cmoat gene in two rat models of hyperbilirubinemia ...

Progressive familial intrahepatic cholestasis (PFIC) comprises a group of rare cholestatic liver disorders of childhood that could lead to liver cirrhosis. Nowadays, the partial biliary diversion procedure is still a therapeutic option in non-cirrhotic children with PFIC1 or PFIC2 after an ineffective ursodeoxycholic acid (UDCA) therapy. However, the relevant disadvantage of the partial external biliary diversion (PEBD) is that adolescent patients could not accept a permanent stoma. In some of them, despite of good clinical and biochemical results of this procedure, the ileal exclusion (IE) procedure had to be performed many years after PEBD. Our aims were to find the most characteristic early microscopic features of the disease as well as to compare changes in the liver biopsy specimens at the time of diagnosis and long-time (more than 10 years) after a surgical procedure. We examined retrospectively 8 liver biopsies from 4 PFIC2 patients comparing the results from the first biopsies done at ...

Breast cancer resistance protein (BCRP, ABCG2) is a member of ABC (ATP-binding cassette) transporter superfamily that occurs in a variety of tissues including liver and small intestine of animals. As BCRP is involved in drug absorption, distribution, and elimination, modulation of its expression may affect the clinical efficacy of drugs. However, little is known about the effects of coccidiosis or colibacillosis infection on the levels of BCRP expression in chickens. Here, we studied the effect of infection with Escherichia coli (E. coli) or Eimeriida mixture (E. necatrix and E. tenella) on the expression levels of ABCG2 mRNA and BCRP in the different segments of small intestine and liver in chickens. Expression of ABCG2 mRNA or BCRP was detected in the entire small intestine and liver of healthy chickens, and the expression levels in liver and ileum were significantly higher than duodenum and jejunum. Infection with E. coli or Eimeriida mixture resulted in significant decrease in ABCG2 mRNA and ...

Swiss drugmakers Roche and Novartis have provided financial backing French gene therapy start-up Vivet Therapeutics, with the latter raising EUR37.5 million (US$41 million) in an initial financing round.. The funds will be used by Vivet to advance a diversified pipeline of gene therapy programs targeting rare, inherited metabolic diseases, including Wilson Disease, progressive familial intrahepatic cholestasis type 2 (PFIC2), progressive familial intrahepatic cholestasis type 3 (PFIC3) and citrullinemia type I.. Vivet, created last year in Paris with a wholly owned subsidiary in Spain, is focused on developing novel gene therapies for rare, inherited metabolic diseases.. Its lead program VTX801, which is expected to enter clinical testing by the end of 2018, targets a condition called Wilson Disease.. This rare genetic disorder is caused by a defective gene in liver cells encoding the ATP7B protein, which reduces the livers ability to regulate copper levels in the liver and other tissues ...

Looking for online definition of ATP-binding cassette, sub-family B (MDR/TAP), member 10 in the Medical Dictionary? ATP-binding cassette, sub-family B (MDR/TAP), member 10 explanation free. What is ATP-binding cassette, sub-family B (MDR/TAP), member 10? Meaning of ATP-binding cassette, sub-family B (MDR/TAP), member 10 medical term. What does ATP-binding cassette, sub-family B (MDR/TAP), member 10 mean?

Some Candida albicans isolates from AIDS patients with oropharyngeal candidiasis are becoming resistant to the azole antifungal agent fluconazole after prolonged treatment with this compound. Most of the C. albicans isolates resistant to fluconazole fail to accumulate this antifungal agent, and this has been considered a cause of resistance. This phenomenon was shown to be linked to an increase in the amounts of mRNA of a C. albicans ABC (ATP-binding cassette) transporter gene called CDR1 and of a gene conferring benomyl resistance (BENr), the product of which belongs to the class of major facilitator multidrug efflux transporters (D. Sanglard, K. Kuchler, F. Ischer, J. L. Pagani, M. Monod, and J. Bille, Antimicrob. Agents Chemother. 39:2378-2386, 1995). To analyze the roles of these multidrug transporters in the efflux of azole antifungal agents, we constructed C. albicans mutants with single and double deletion mutations of the corresponding genes. The mutants were tested for their ...

Purpose: : To investigate the progression in Stargardt-fundus flavimaculatus (S-FFM). Methods: : A longitudinal study of 31 patients with S-FFM was undertaken. The mean age of our patients at the initial examination was 28.8 years old (11-50) with a mean follow-up interval of 9.3 years (5-11). Electrophysiological tests, including pattern, focal and full-field electroretinogram (ERG) were performed, as was a clinical ophthalmic examination and fundus autofluorescence imaging. The classification which we previously reported was used for assessment; group 1: dysfunction confined to the macula; group 2: macular and generalized cone dysfunction; group 3: macular, generalized cone and generalized rod dysfunction. At the initial examination, there were 13 patients in group 1, 8 patients in group 2, and 10 patients in group 3. Analysis of the ATP-binding cassette transporter gene (ABCA4) was performed in the majority of the cohort. Results: : Three of 13 patients from group 1 progressed to group 2, and ...

Retinoic acids regulate the reverse cholesterol transport by inducing the ATP binding cassette transporter A1 (ABCA1) dependent cholesterol efflux in macrophages, neuronal as well as intestine cells. In the present study, we aim to test the effect of all trans retinoic acid (ATRA) on ABCA1 expression in human CD4+ T cells and the involvement of cholesterol in ATRA mediated anti-HIV effect. Treatment with ATRA dramatically up-regulated ABCA1 expression in CD4+ T cells in a time and dose dependent manner. The expression of ABCA1 paralleled with increased ABCA1-dependent cholesterol efflux. This induction was dependent on T cell receptor (TCR) signaling and ATRA failed to induce ABCA1 expression in resting T cells. Moreover, ATRA and liver X receptor (LXR) agonist-TO-901317 together had synergistic effect on ABCA1 expression as well as cholesterol efflux. Increased ABCA1 expression was associated with lower cellular cholesterol staining. Cells treated with either ATRA or TO-901317 were less vulnerable to

Because little is known about ABC transporter functions in insects, we examined these proteins in T. castaneum, a well-established and powerful genomic insect model that is highly susceptible to systemic RNAi [22]. Bioinformatic analyses revealed that the ABC transporter superfamily comprises 73 genes in T. castaneum, which group into eight subfamilies. With 35 members, subfamily C constitutes the largest ABC transporter subfamily in T. castaneum. Compared with ABCC subfamilies in other insects, TcABCC appears to have undergone a recent expansion on chromosome 5. In insects, ABC transporters have been implicated in insecticide resistance by increasing the efflux capacity for xenobiotics [37]. This suggests the possibility that the known propensity of this species to develop insecticide resistance might be related to the expansion of subfamily C genes. Indeed, extensive forms of gene duplication (or amplification) are frequently observed for genes involved in insecticide detoxification, including ...

Oxidized sterols consumed in the diet or formed on low-density lipoprotein (LDL) are toxic to endothelial cells and macrophages and are thought to have a central role in promoting atherogenesis. The ATP-binding cassette transporter ABCG1 was recently shown to promote efflux of cholesterol from macrophages to HDL. We show that HDL protects macrophages from apoptosis induced by loading with free cholesterol or oxidized LDL (oxLDL). The protective effect of HDL was reduced in Abcg1−/− macrophages, especially after loading with oxidized LDL. Similarly, HDL exerted a protective effect against apoptosis induced by 7-ketocholesterol, the major oxysterol present in oxLDL and atherosclerotic lesions, in Abcg1+/+ but not in Abcg1−/− macrophages. In transfected 293 cells, efflux of 7-ketocholesterol was completely dependent on expression of ABCG1 and presence of HDL in media. In contrast, ABCA1 and apoA-1 did not stimulate efflux of 7-ketocholesterol into media. HDL stimulated efflux of ...

Differential Effects of Chrysin on Nitrofurantoin Pharmacokinetics Mediated by Intestinal Breast Cancer Resistance Protein in Rats and Mice

The LXRs (liver X receptors) (LXRα and LXRβ) are nuclear hormone receptors that are activated by oxysterols, endogenous oxidative metabolites of cholesterol. These receptors regulate an integrated network of genes that control whole body cholesterol and lipid homoeostasis. A brief overview of the mechanism of this regulation by LXRs in the liver, macrophage and intestine will be outlined, followed by data from our recent work demonstrating that LXRα is crucial in maintaining adrenal cholesterol homoeostasis. In the adrenal gland, oxysterols are formed as intermediates in the conversion of cholesterol into steroid hormones and can act as endogenous activators of LXR. We have found using both gain- and loss-of-function models that LXR acts to maintain free cholesterol below toxic levels in the adrenal gland, through the co-ordinated regulation of genes involved in cholesterol efflux [ABCA1 (ATP-binding-cassette transporter A1)], storage (sterol-regulatory-element-binding protein-1c and ...

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ALD subfamily, which is involved in peroxisomal import of fatty acids and/or fatty acyl-CoAs in the organelle. All known peroxisomal ABC transporters are half transporters which require a partner half transporter molecule to form a functional homodimeric or heterodimeric transporter. This peroxisomal membrane protein is likely involved in the peroxisomal transport or catabolism of very long chain fatty acids. Defects in the human gene have been identified as the underlying cause of adrenoleukodystrophy, an X-chromosome recessively inherited demyelinating disorder of the nervous system. [provided by RefSeq, Jul 2008 ...

P-glycoprotein (P-gp) is a member of the ATP-Binding Cassette transporter superfamily and mediates transmembrane efflux of many drugs. Since it is involved in multi-drug resistance activity in various cancer cells, the development of P-gp inhibitor is one of the major concerns in anticancer therapy. Human P-gp protein has at least two functional drug binding sites that are called H site and R site, hence it has multi-binding-specificities. Though the amino acid residues that constitute in drug binding pockets have been proposed by previous experimental evidences, the shapes and the binding poses are not revealed clearly yet. In this study, human P-gp structure was built by homology modeling with available crystal structure of mouse P-gp as a template and docking simulations were performed with inhibitors such as verapamil, hoechst33342, and rhodamine123 to construct the interaction between human P-gp and its inhibitors. The docking simulations were performed 500 times for each inhibitor, and

In progressive familial intrahepatic cholestasis type 2 (PFIC-2), severe steatorrhea is often documented. However, pancreatic exocrine secretion has not yet bee

From NCBI Gene:. The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ALD subfamily, which is involved in peroxisomal import of fatty acids and/or fatty acyl-CoAs in the organelle. All known peroxisomal ABC transporters are half transporters which require a partner half transporter molecule to form a functional homodimeric or heterodimeric transporter. This peroxisomal membrane protein likely plays an important role in peroxisome biogenesis. Mutations have been associated with some forms of Zellweger syndrome, a heterogeneous group of peroxisome assembly disorders. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]. From UniProt: ...

The EGFR pathway has been an attractive target because it is dysregulated in a significant fraction of malignant gliomas through overexpression, amplification, and activating mutations (Rich et al., 2004). Moreover, recent studies have demonstrated that EGFRvIII is required for tumor maintenance in glioma (Mukasa et al., 2010). The EGFR tyrosine kinase inhibitor gefitinib has been evaluated in a number of clinical trials for GBM; however, results have been disappointing (Rich et al., 2004; Lieberman et al., 2004). The failure of gefitinib raises questions pertaining to delivery of drug to its target. Active efflux at the BBB could prevent drugs from attaining therapeutic levels in the brain and is probably one of the main reasons behind resistance to chemotherapy. It has been shown that several other tyrosine kinase inhibitors are avid substrates for P-gp and BCRP and that their brain distribution is limited due to active efflux out of the brain (Dai et al., 2003; Chen et al., 2009; Lagas et ...

The Original One-Hour Scripted Drama, Which Launched as the Highest-Rated Original Series Debut in the Networks History in Early June, Continues to Grow In Ratings Throughout Its First Three Episodes. Burbank, CA (June 28, 2010) - ABC Family has ordered 12 additional episodes of the networks hit one-hour series, Pretty Little Liars, announced Kate Juergens, Executive Vice President, Original Programming & Development. The order will bring the shows first season to a total of 22 episodes.. Pretty Little Liars is a break-out hit for the network, said Juergens. Were thrilled that our Millennial viewers have responded so strongly to the show. Its a perfect fit with the networks strong slate of original scripted dramas, including The Secret Life of the American Teenager and Make It or Break It.. One of cables biggest breakout hits of summer, Pretty Little Liars launched as ABC Familys No. 1 series debut ever in Adults 18-34 (837,000), Women 18-34 (657,000), Viewers 12-34 (1.7 ...

Phospho-glycoprotein (P-gP) is a polytopic plasma membrane protein whose overexpression causes multidrug resistance (MDR) responsible for the failure of cancer chemotherapy. P-gp 170 is a member of the ATP-binding cassette (ABC) transporter superfamily and has two potentially interesting regions for drugs interfering with its efflux function, namely the oligosaccharides on the first extracellular loop with unknown function and the two intracellular ATP-binding regions providing the energy for drug efflux function. The polylactoseamine oligosaccharides on the first loop can specifically bind the tomato lectin (TL). The P-gp efflux activities of TL-pre-treated MDR resistant cells were measured in the presence of structurally unrelated resistance modifiers such as phenothiazines, terpenoids and carotenoids. The inhibition of efflux activity was measured via the increased rhodamine uptake by mouse lymphoma cells transfected in human MDR1 gene and in human brain capillary endothelial cells. The ...

The overlap in the membrane localization and substrate specificities of Bcrp and P-gp has suggested their cooperation in the active efflux in the blood-tissue barriers. A considerable increase in the accumulation of common substrates in the brain of Mdr1a/1b(−/−)/Bcrp(−/−) mice compared with that observed in either Mdr1a/1b(−/−) or Bcrp(−/−) mice has been interpreted as synergistic effect. The present study investigated this synergistic effect kinetically by using erlotinib, flavopiridol, and mitoxantrone as test compounds. Because Cisternino et al. (2004) reported an induction of Bcrp mRNA in the brain capillaries from Mdr1a/1b(−/−) mice, quinidine and dantrolene were used as probes for P-gp and Bcrp, respectively, to examine their adaptive regulation in the knockout strain.. Adaptive regulation of P-gp at the BBB and BTB of Bcrp(−/−) mice is negligible because neither the Cbrain/Cplasma nor the Ctestis/Cplasma of quinidine changed in Bcrp(−/−) mice compared with the ...

In this study, we performed a mutation analysis of the ABCR gene of 80 unrelated AMD patients and 100 race and age matched control subjects. Of 51 exons of the ABCR gene, 10 that have been reported to have AMD associated mutations were studied.3 The only missense mutation found was a T1428M mutation in exon 29. Allikmetset al reported that this mutation was found in one of 167 AMD patients, and that no such mutation was found in the general population.3 However, in our series, seven of 80 (8.8%) AMD patients and eight of 100 (8.0%) of the control group did, in fact, showed this mutation (Table 1), which was not a statistically significant difference. Other alterations found were mostly polymorphisms or sequence variations. These were found in exons 23, 41, 43, and did not correspond to the 13 AMD associated mutations reported by Allikmets et al.3Apparently, there is heterogeneity in the ABCR gene. Indeed, all of the AMD and the control subjects in our series showed different nucleotide sequences ...

The ATP-binding cassette transporters P-glycoprotein (ABCB1 MDR1) and multidrug resistance protein 4 (MRP4) efflux irinotecan and its active metabolite SN-38 genotype was a significant covariate for the clearance of both irinotecan Epigallocatechin gallate lactone and SN-38 Epigallocatechin gallate lactone. of the topoisomerase Epigallocatechin gallate I enzyme [2]. SN-38 undergoes glucuronic acid Rabbit polyclonal to TranscriptionfactorSp1. … Continue reading The ATP-binding cassette transporters P-glycoprotein (ABCB1 MDR1) and multidrug resistance protein. ...

AUTOSOMAL RECESSIVE STARGARDT DISEASE (STGD1) is the most common inherited juvenile macular degeneration.1 Most patients develop bilateral loss of vision in childhood or early adulthood. This subtype of Stargardt disease is caused by mutations in the ABCA4 gene, which encodes a retina-specific transporter protein (ABCR) in the rims of rod and cone photoreceptor outer segment discs.2-4 Retinal degeneration in ABCA4-linked Stargardt disease is believed to result from the toxic effects of lipofuscin that accumulates in the retinal pigment epithelium (RPE) and the subsequent degeneration of photoreceptors.5. Light can induce photochemical injury at the ocular fundus. Depending on the level and duration of the irradiance, the primary site of damage can be either the photoreceptors or the RPE.6 In ABCA4-linked retinopathies, products generated by the visual cycle accumulate and contribute to retinal damage via both direct toxic effects and increased photosensitivity. A major fluorophore of lipofuscin, ...

ATP-sensitive potassium (KATP) channels comprise four pore-forming Kir6.2 subunits and four modulatory sulfonylurea receptor (SUR) subunits. The latter belong to the ATP-binding cassette family of transporters. KATP channels are inhibited by ATP (or ADP) binding to Kir6.2 and activated by Mg-nucleotide interactions with SUR. This dual regulation enables the KATP channel to couple the metabolic state of a cell to its electrical excitability and is crucial for the KATP channels role in regulating insulin secretion, cardiac and neuronal excitability, and vascular tone. Here, we review the regulation of the KATP channel by adenine nucleotides and present an equilibrium allosteric model for nucleotide activation and inhibition. The model can account for many experimental observations in the literature and provides testable predictions for future experiments.

Introduction Multidrug resistance (MDR) is a major cause of treatment failure and mortality in cancer patients. Breast cancer is the most prevalent cancer among women and the second leading cause of death in cancer. The most widely used treatment of breast cancer is chemotherapy, while the success of chemotherapy in breast cancer patients is also seriously limited by the development of MDR [1]. One well-known mechanism of MDR is the over-expression of ATP-binding cassette transporters such as multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein 1 (MRP1), Sunitinib lung resistance protein (LRP). and the breast cancer resistance protein (BCRP) [2-7]. P-glycoprotein (P-gp), which is encoded by the MDR1, is the most extensively studied drug transporter. It is an integral membrane glycoprotein with a molecular mass of 170 kDa and has been postulated to function as a pump that removes hydrophobic anticancer agents from drug-resistant cells, thus promoting MDR [8]. The novel gene ...

TY - JOUR. T1 - No association of ABCB1 polymorphisms with drug-refractory epilepsy in a north Indian population. AU - Lakhan, R.. AU - Misra, U. K.. AU - Kalita, J.. AU - Pradhan, S.. AU - Gogtay, N. J.. AU - Singh, M. K.. AU - Mittal, B.. N1 - Funding Information: The study was supported by a grant received from the Department of Biotechnology, Government of India, and a fellowship provided by CSIR, New Delhi, India.. PY - 2009/1. Y1 - 2009/1. N2 - Multiple drug resistance is a common problem in the treatment of epilepsy, and approximately 30% of patients continue to have seizures despite all therapeutic interventions. Among various classes of drug transporters, genetic variants of P-glycoprotein (P-gp) encoded by the ABCB1 (ATP-binding cassette subfamily B member 1) gene have been associated with drug-refractory epilepsy. Our aim was to investigate the effect of the 1236C,T(rs1128503), 2677G,T/A(rs2032582), and 3435C,T(rs1045642) single-nucleotide polymorphisms of ABCB1 (or MDR1) on drug ...

In the study of motor proteins, the molecular mechanism of mechanochemical coupling, as well as the cellular role of these proteins, is an important issue. To assess these questions we introduced cDNA of wild-type and site-directed mutant kinesin heavy chains into fibroblasts, and analyzed the behavior of the recombinant proteins and the mechanisms involved in organelle transports. Overexpression of wild-type kinesin significantly promoted elongation of cellular processes. Wild-type kinesin accumulated at the tips of the long processes, whereas the kinesin mutants, which contained either a T93N- or T93I mutation in the ATP-binding motif, tightly bound to microtubules in the center of the cells. These mutant kinesins could bind to microtubules in vitro, but could not dissociate from them even in the presence of ATP, and did not support microtubule motility in vitro, thereby indicating rigor-type mutations. Retrograde transport from the Golgi apparatus to the endoplasmic reticulum, as well as ...

Mutations in the ATP8B1 gene can cause benign recurrent intrahepatic cholestasis 1 (BRIC1) or progressive familial intrahepatic cholestasis 1 (PFIC1), commonly known as ATP8B1 deficiency. ATP8B1 is an aminophospholipid flippase, maintaining membrane asymmetry. In ATP8B1 deficiency the activity of the bile salt export pump (BSEP) which pumps bile salts out ... read more of the hepatocytes into the bile duct is decreased, leading to accumulation of bile salts and cell damage. However, the mechanism by which ATP8B1 defects causes cholestasis is unknown. Involvement of the nuclear receptor FXR or reduced membrane stability and consequent decreased BSEP activity have been suggested. Proper ATP8B1 folding and association with CDC50A is required for ATP8B1 to exit the ER and traffic to the plasma membrane. It was recently demonstrated that ATP8B1 mutations often result in protein misfolding and subsequent ER retention and protein degradation. Molecular chaperones facilitate protein folding and ...

The clearance of apoptotic cells occurs throughout the lifespan of multicellular organisms and is important for development during embryogenesis, the maintenance of tissue integrity and function, and the resolution of inflammation (deCathelineau and Henson, 2003). Here, we report that macrophage ABCA7 enhances the clearance of apoptotic cells in vitro and in vivo. ABCA7 and LRP1 move to the cell surface after stimulation with C1q or apoptotic cells and localize to membrane ruffles or phagocytic cups, respectively. However, ABCA7 also localizes to phagocytic membranes during FcR-mediated phagocytosis, in which ABCA7 levels are not rate limiting. More important, ABCA7 is required for optimal ligand-induced signaling through LRP1, as shown by C1q-induced ERK phosphorylation and for sustained ERK phosphorylation during phagocytosis of apoptotic cells. Finally, ERK phosphorylation itself is shown to be essential for phagocytosis of apoptotic cells but not for FcR-mediated phagocytosis, suggesting a ...

Introduction: The breast cancer resistance protein BCRP, encoded by ABCG2, is a member of the ABC transporter family and is well-known for its contribution to multi-drug resistance in cancer. Although BCRP expression is altered in various cancer types, its role and function in cancer, independent from drug efflux, remains largely elusive. In this study, we aimed to elucidate regulatory mechanisms of ABCG2 expression and its biological relevance in clear cell renal cell carcinoma (ccRCC) as well as associations with response to sunitinib treatment in patients with metastatic ccRCC.. Experimental Procedures: Data from the ccRCC cohort of The Cancer Genome Atlas (TCGA) was used to assess ABCG2 mRNA expression (n=463), DNA methylation (n=288) and genetic variants present in tumor tissue (n=326) within the ABCG2 gene region. An independent ccRCC cohort of 64 patients was used for the analysis of ABCG2 mRNA and protein expression by TaqMan quantitative real time PCR or immunohistochemical staining of ...

ABC transporters play a key role in protecting the brain parenchyma by exerting their action at the blood-brain barrier (BBB). However, they also block the entry of therapeutic drugs. One of the key transporters playing this role is ABCG2. While other ABC transporters can be studied through PET, no probe exists for imaging ABCG2 function. D-luciferin, the endogenous substrate of fLuc, has been shown to demonstrate decreased bioluminescence in ABCG2-expressing cells, and low brain distribution. We hypothesized that we can image ABCG2 function at the BBB using bioluminescent imaging in transgenic mice expressing fLuc in the brain. In vitro, accumulation of D-luciferin was lowest in cells overexpressing ABCG2, and the accumulation increased when co-administered Ko143, a potent and selective ABCG2 inhibitor. Using a mouse model expressing fLuc behind the GFAP promoter, mainly expressed in astrocytes of the brain, D-luciferin BLI signal was found to be low. However, it increased in a dose-dependent ...

Background. Our aim was to determine whether the common variants within the coding sequence of ABCA1 gene affects low plasma high-density lipoprotein cholesterol (HDL-C) levels in Turkish patients with coronary artery disease (CAD). The study group was composed of 552 CAD patients, of which 251 had HDL-C levels 40 mg/dL. ...

The bile salt export pump (BSEP) is an ABC-transporter expressed at the canalicular membrane of hepatocytes. Its physiological role is to expel bile salts into the canaliculi from where they drain into the bile duct. Inhibition of this transporter may lead to intrahepatic cholestasis. Predictive computational models of BSEP inhibition may allow for fast identification of potentially harmful compounds in large databases. This article presents a predictive in silico model based on physicochemical descriptors that is able to flag compounds as potential BSEP inhibitors. This model was built using a training set of 670 compounds with available BSEP inhibition potencies. It successfully predicted BSEP inhibition for two independent test sets and was in a further step used for a virtual screening experiment. After in vitro testing of selected candidates, a marketed drug, bromocriptin, was identified for the first time as BSEP inhibitor. This demonstrates the usefulness of the model to identify new BSEP ...

BmrA from Bacillus subtilis is a half-size ABC (ATP-binding cassette) transporter involved in multidrug resistance. Although its supramolecular organization has been investigated after reconstitution in a lipid bilayer environment, and shows a dimeric and possibly a tetrameric form, the precise quaternary structure in a detergent-solubilized state has never been addressed. In the present study, BmrA was purified from Escherichia coli membranes using an optimized purification protocol and different detergents. Furthermore, the ATPase activity of BmrA and the quantity of bound lipids and detergent were determined, and the oligomeric state was analysed using SEC (size-exclusion chromatography) and analytical ultracentrifugation. The activity and the quaternary structure of BmrA appeared to be strongly influenced by the type and concentration of the detergent used. SEC data showed that BmrA could be purified in a functional form in 0.05 and 0.01% DDM (n-dodecyl-β-D-maltoside) and was homogeneous ...

The ATP-binding cassette (ABC) transporter ABCB1, encoded by the multidrug resistance gene MDR1, is expressed on brain microvascular endothelium and several types of epithelium, but not on endothelia outside the CNS. It is an essential component of the blood-brain barrier. The aim of this study was to identify cell-specific controls on the transcription of MDR1 in human brain endothelium. Reporter assays identified a region of 500bp around the transcription start site that was optimally active in brain endothelium. Chromatin immunoprecipitation identified Sp3 and TFIID associated with this region and EMSA (electrophoretic mobility shift assays) confirmed that Sp3 binds preferentially to an Sp-target site (GC-box) on the MDR1 promoter in brain endothelium. This result contrasts with findings in other cell types and with the colon carcinoma line Caco-2, in which Sp1 preferentially associates with the MDR1 promoter. Differences in MDR1 transcriptional control between brain endothelium and Caco-2 ...

The ATP-binding cassette (ABC) transporters form one of the largest known protein families, and are widespread in bacteria, archaea, and eukaryotes. They couple ATP hydrolysis to active transport of a wide variety of substrates such as ions, sugars, lipids, sterols, peptides, proteins, and drugs. The structure of a prokaryotic ABC transporter usually consists of three components; typically two integral membrane proteins each having six transmembrane segments, two peripheral proteins that bind and hydrolyze ATP, and a periplasmic (or lipoprotein) substrate-binding protein. Many of the genes for the three components form operons as in fact observed in many bacterial and archaeal genomes. On the other hand, in a typical eukaryotic ABC transporter, the membrane spanning protein and the ATP-binding protein are fused, forming a multi-domain protein with the membrane-spanning domain (MSD) and the nucleotide-binding domain (NBD ...

Expression of the multidrug transporter P-glycoprotein (P-gp) is one of the major causes of multidrug resistance in cancer cells. P-gp is a 170-kDa membrane protein encoded by the MDR1 gene in humans. Based on its sequence and domain organization, P-gp is classified as a member of ATP binding cassette superfamily; it consists of two symmetrical halves, each half containing six transmembrane (TM) domains and a cytoplasmic nucleotide binding domain. Although most members of the ABC transporter family have stringent substrate specificities, P-gp recognizes many compounds, including anthracyclines (e.g., doxorubicin and daunomycin), vinca alkaloids (e.g., vincristine and vinblastine), antibiotics (e.g., actinomycin D), circular and toxic peptides (e.g., valinomycin and gramicidin), and relatively noncytotoxic agents such as verapamil, azidopine, quinidine, and cyclosporin A. These P-gp substrates have no common chemical structure. They are all low-molecular-weight nonanionic hydrophobic or ...

EXCLUSIVE: What if Sex and the Citys Carrie Bradshaw was dying of cancer? That in essence is the premise of the Mexican drama series Terminales, which is being adapted by ABC Family. Lionsgate TV and Kapital Entertainment are producing the U.S.

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Predicted to have ATPase-coupled transmembrane transporter activity and lipid transporter activity. Involved in neutral lipid metabolic process. Localizes to endoplasmic reticulum. Orthologous to human ABCA17P (ATP binding cassette subfamily A member 17, pseudogene ...

This work is the first description of the expression of human BCRP in X. laevis oocytes and demonstrates that this heterologous expression system is a valid model for examining the physical and functional characteristics of this ABC half transporter. X. laevis oocytes injected with BCRP cRNA synthesize a protein with the molecular mass of glycosylated BCRP and the immunological characteristics of native human BCRP protein. Our results further demonstrate that oocytes injected with mutant R482T or wild-type BCRP cRNA express BCRP in the oocyte plasma membrane, as evidenced by confocal immunofluorescence microscopic analysis. Accumulation and efflux assays using various BCRP substrate molecules indicate that the oocyte-expressed BCRP functions in a manner analogous to that observed in mammalian systems. Moreover, the X. laevis model indicates that a mutation of serine at codon 187 in the ABC-signature motif of BCRP is not only devoid of transporter activity but also serves in a manner analogous to ...

Among the various transporter genes identified in the C. albicans genome (7, 8), there are overwhelming clinical and experimental evidences to suggest that out of 28 ABC transporters, only two of its members, CaCdr1p and CaCdr2p, and only CaMdr1p out of a total 95 of members of MFS transporters are major determinants of MDR (18, 23). Therefore, the search for novel and potent modulators which can block and reverse the drug extrusion mediated by these efflux proteins represents an attractive strategy of anti-Candida therapy. While there are several compounds which are shown to reverse MDR mediated by Pgp (human homologue of CaCdr1p and CaCdr2p) and are at various stages of clinical trials, there are not many instances of compounds which could inhibit/reverse drug extrusion mediated by fungal multidrug transporters (12, 14, 22, 31). We have been exploring modulators/inhibitors of MDR pump proteins which could block the efflux of drugs from fungal cells. For example, we have earlier reported that ...

One of the main obstacles in tumor therapy is multiple drug resistance (MDR) and an underlying mechanism of MDR is up-regulation of the transmembrane ATP-binding cassette (ABC) transporter proteins, especially P-glycoprotein (P-gp). In the synergistic treatment of siRNA and anti-cancer drug doxorubicin, it is crucial that both the siRNA and doxorubicin are simultaneously delivered to the tumor cel ...

ABCB10, or ATP binding cassette sub-family B member 10, is a protein localized in the mitochondrial inner membrane. It belongs to the ABC transporter family whose members are proteins that facilitate substrate transport across various biological membranes. It has been found that ABCB10 is required for normal heme biosynthesis during erythroid differentiation and also plays a role in protection against the damage caused by reactive oxygen species (ROS) production. This protective effect exists both in the erythrocyte development and in the heart recovery after the ischemia-reperfusion injury. However, as an ABC transporter, its transported substrates are not known, neither is the mechanism by which ABCB10 plays a role in protection against ROS damage. In this dissertation an 8-azido-ATP photolabeling system is established to study the ATP binding and hydrolysis properties of ABCB10. Using this approach, it is found that the conserved amino acid residues Gly497 and Lys498 in the Walker A motif of ...

This year, Shawnee Town will celebrate the iconic 1920s with our new series, History on Tap, bringing together presentations on subjects that the decade is most readily associated with - sex, gangsters, bootlegging, and baseball. A different local brewery will be on hand each of the four History on Tap evenings this year to showcase their wares. Short skirts, shorter hair, revealing lingerie, and loose morals are what most of us associate with the decade of the flapper. Was this the norm or that of a small group of pampered young women flouting their angst at Mama? Come and find out at our first History on Tap!. Price: 5. ...