Understanding of human ATP binding cassette superfamily and novel multidrug resistance modulators to overcome MDR

2018 ◽  
Vol 100 ◽  
pp. 335-348 ◽  
Author(s):  
Imran Shair Mohammad ◽  
Wei He ◽  
Lifang Yin
Keyword(s):  
Multidrug Resistance ◽  
Atp Binding ◽  
Resistance Modulators ◽  
Atp Binding Cassette

scholarly journals Human ATP-Binding Cassette Transporter TaqMan Low-Density Array: Analysis of Macrophage Differentiation and Foam Cell Formation

2006 ◽  
Vol 52 (2) ◽  
pp. 310-313 ◽  
Author(s):  
Thomas Langmann ◽  
Richard Mauerer ◽  
Gerd Schmitz
Keyword(s):  
Multidrug Resistance ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Metabolic Regulation ◽  
Foam Cell ◽  
Expression Patterns ◽  
Foam Cell Formation ◽  
Atp Binding ◽  
Low Density ◽  
Atp Binding Cassette

Abstract Background: ATP-binding cassette (ABC) transporters cause various diseases and regulate many physiologic processes, such as lipid homeostasis, iron transport, and immune mechanisms. Several ABC transporters are involved in bile acid, phospholipid, and sterol transport, and their expression is itself controlled by lipids. In addition, ABC proteins mediate drug export in tumor cells and promote the development of multidrug resistance. Methods: We created an ABC Transporter TaqMan Low-Density Array based on an Applied Biosystems 7900HT Micro Fluidic Card. We used a 2-μL reaction well with 2 ng of sample. To evaluate this method for lipidomic research and to characterize expression patterns of ABC transporters in cells relevant for atherosclerosis research, we monitored mRNA expression in human primary monocytes, in vitro–differentiated macrophages, and cells stimulated with the liver-X-receptor and retinoid-X-receptor agonists T0901317 and 9-cis retinoic acid, mimicking sterol loading. Results: The method enabled simultaneous analysis of 47 human ABC transporters and the reference gene 18S rRNA in 2 replicates of 4 samples per run. Conclusions: The new system uses only 2 ng of sample and small volumes of reagent, and the precaptured primers and probes avoided labor-intensive pipetting steps. The ABC Transporter TaqMan Low-Density Array may be a useful tool to monitor dysregulated ABC transporter mRNA profiles in human lipid disorders and cancer-related multidrug resistance and to analyze the pharmacologic and metabolic regulation of ABC transporter expression important for drug development in large-scale screening approaches.

Zafirlukast antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance

2012 ◽  
Vol 23 (8) ◽  
pp. 865-873 ◽  
Author(s):  
Yue-Li Sun ◽  
Rishil J. Kathawala ◽  
Satyakam Singh ◽  
Kelvin Zheng ◽  
Tanaji T. Talele ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Atp Binding ◽  
Atp Binding Cassette

scholarly journals HG-829 Is a Potent Noncompetitive Inhibitor of the ATP-Binding Cassette Multidrug Resistance Transporter ABCB1

2012 ◽  
Vol 72 (16) ◽  
pp. 4204-4213 ◽  
Author(s):  
Gisela Caceres ◽  
Robert W. Robey ◽  
Lubomir Sokol ◽  
Kathy L. McGraw ◽  
Justine Clark ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Atp Binding ◽  
Noncompetitive Inhibitor ◽  
Multidrug Resistance Transporter ◽  
Atp Binding Cassette

scholarly journals The role of dietary flavonoids for modulation of ATP binding cassette transporter mediated multidrug resistance

eFood ◽  
2021 ◽  
Author(s):  
Hui Teng ◽  
Hongting Deng ◽  
Yuanju He ◽  
Qiyan Lv ◽  
Lei Chen
Keyword(s):  
Multidrug Resistance ◽  
Abc Transporters ◽  
Systemic Circulation ◽  
Atp Binding ◽  
Cancer Resistance ◽  
Associated Proteins ◽  
Food Toxin ◽  
Atp Binding Cassette

Flavonoids are widely existing compounds with enormous pharmacological effects from food and medicine. However, the low bioavailability in intestinal absorption and metabolism limits their clinical application. Intestinal efflux ABC (ATP binding cassette) transporters, including P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs), act as "pumping doors" to regulate the efflux of flavonoids from intestinal epithelial cells into the intestinal cavity or the systemic circulation. The present review describes the critical effect of ABC transporters involved in the efflux of flavonoids which depend on its efflux direction. And the role of flavonoids for modulation of intestinal ABC transporters was emphasized and several examples were given. We summarized that the resistance effect of flavonoid-mediated multidrug on ABC transporters may influence the bioavailability of drugs, bioactive ingredients and/or toxic compounds upon dietary uptake. Meanwhile, flavonoids functionalized as reversing agents of the ABC transporter may be an important mechanism for unexpected food-drug, food-toxin or food-food interactions. The overview also indicates that elucidation of the action and mechanism of the intestinal metabolic enzymes-efflux transporters coupling will lay a foundation for improving the bioavailability of flavonoids <i>in vivo</i> and increasing their clinical efficacy.

A Novel ATP-Binding Cassette Transporter Involved in Multidrug Resistance in the Phytopathogenic FungusPenicillium digitatum

1998 ◽  
Vol 64 (10) ◽  
pp. 3983-3988 ◽  
Author(s):  
Ryoji Nakaune ◽  
Kiichi Adachi ◽  
Osamu Nawata ◽  
Masamitsu Tomiyama ◽  
Katsumi Akutsu ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Resistant Strain ◽  
Pathogenic Fungus ◽  
Penicillium Digitatum ◽  
Atp Binding ◽  
Multidrug Resistance Gene ◽  
Gene Encoding ◽  
Amino Acid Homology ◽  
Resistant Strains ◽  
Atp Binding Cassette

ABSTRACT Demethylation inhibitor (DMI)-resistant strains of the plant pathogenic fungus Penicillium digitatum were shown to be simultaneously resistant to cycloheximide, 4-nitroquinoline-N-oxide (4NQO), and acriflavine. APMR1 (Penicillium multidrug resistance) gene encoding an ATP-binding cassette (ABC) transporter (P-glycoprotein) was cloned from a genomic DNA library of a DMI-resistant strain (LC2) ofPenicillium digitatum by heterologous hybridization with a DNA fragment containing an ABC-encoding region from Botrytis cinerea. Sequence analysis revealed significant amino acid homology to the primary structures of PMR1 (protein encoded by thePMR1 gene) and ABC transporters of Saccharomyces cerevisiae (PDR5 and SNQ2), Schizosaccharomyces pombe(HBA2), Candida albicans (CDR1), and Aspergillus nidulans (AtrA and AtrB). Disruption of the PMR1 gene of P. digitatum DMI-resistant strain LC2 demonstrated that PMR1 was an important determinant of resistance to DMIs. The effective concentrations inhibiting radial growth by 50% (EC50s) and the MICs of fenarimol and bitertanol for the PMR1disruptants (Δpmr1 mutants) were equivalent to those for DMI-sensitive strains. Northern blot analysis indicated that severalfold more PMR1 transcript accumulated in the DMI-resistant strains compared with those in DMI-sensitive strains in the absence of fungicide. In both DMI-resistant and -sensitive strains, transcription of PMR1 was strongly enhanced within 10 min after treatment with the DMI fungicide triflumizole. These results suggested that the toxicant efflux system comprised of PMR1 participates directly in the DMI resistance of the fungus.

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