A5030180282- Drug Transport and Resistance Mechanisms
- Erythrocyte Function and Pathophysiology
- RNA Interference and Gene Delivery
- Pharmacological Effects and Toxicity Studies
- Ion channel regulation and function
- HIV/AIDS drug development and treatment
- Trace Elements in Health
- Cholesterol and Lipid Metabolism
- Lipid Membrane Structure and Behavior
- Pluripotent Stem Cells Research
- Pancreatic function and diabetes
- DNA and Nucleic Acid Chemistry
- Cancer therapeutics and mechanisms
- Amino Acid Enzymes and Metabolism
- CRISPR and Genetic Engineering
- Hemoglobinopathies and Related Disorders
- Pediatric Hepatobiliary Diseases and Treatments
- Gout, Hyperuricemia, Uric Acid
- Genomics and Rare Diseases
- Metabolism and Genetic Disorders
- Neuroscience and Neuropharmacology Research
- Cystic Fibrosis Research Advances
- Pregnancy and Medication Impact
- Epigenetics and DNA Methylation
- Renal and related cancers
HUN-REN Research Centre for Natural Sciences
2016-2025
Semmelweis University
2016-2025
Institute of Molecular Life Sciences
2015-2024
University of Pecs
2024
Hungarian Academy of Sciences
2013-2022
Eötvös Loránd University
2021
Széchenyi István University
2020
Institute of Biophysics
2016-2018
Czech Academy of Sciences, Institute of Biophysics
2016
Hungarian National Blood Transfusion Service
1991-2014
Our studies demonstrate that the ABC transporter and marker of stem progenitor cells known as breast cancer resistance protein (BCRP or ABCG2) confers a strong survival advantage under hypoxic conditions. We show that, hypoxia, from Bcrp(-)/(-)mice have reduced ability to form colonies compared with Bcrp(+/+) mice. Blocking BCRP function in markedly reduces However, blocking heme biosynthesis reverses susceptibility Bcrp(-/-) cells, finding indicates molecules (i.e. porphyrins) are...
Drug-resistant tumor cells actively extrude a variety of chemotherapeutic agents by the action multidrug resistance (MDR1) gene product, plasma membrane P-glycoprotein.In this report we show that expression human MDRl in cultured
In this report we show that NIH-3T3 mouse fibroblasts stably expressing the human multidrug transporter (MDR1 or P-glycoprotein), in contrast to control cells, actively extrude hydrophobic acetoxymethyl ester (AM) derivatives used for cellular loading of various fluorescent calcium and pH indicators. This dye extrusion is blocked by competing substrates inhibitors transporters, e.g. verapamil, vincristine, sodium orthovanadate, oligomycin, a monoclonal anti-MDR1 antibody. The hydrophilic...
Tyrosine kinase inhibitors (TKIs) are promising new agents for specific inhibition of malignant cell growth and metastasis formation. Because most the TKIs have to reach an intracellular target, membrane transporters may significantly modulate their effectiveness. In addition, hydrophobic interact with so-called multidrug thus alter cellular distribution unrelated pharmacological agents. present work, we show that certain TKIs, already in clinical phase drug development, directly ABCG2...
The human multidrug resistance protein (MRP1) causes drug by extruding drugs from tumor cells. In addition to an MDR-like core, MRP1 contains N-terminal membrane-bound region (TMD0) connected the core a cytoplasmic linker (L0). We have studied truncated versions containing either alone or plus L0, produced in baculovirus-insect (Sf9) cell system. Their function was examined isolated membrane vesicles. Full-length showed ATP-dependent, vanadate-sensitive accumulation of leukotriene C4 and...
The human multidrug resistance protein MRP1 and its homolog, MRP2, are both suggested as being involved in cancer drug the transport of organic anions. We expressed MRP2 in<i>Spodoptera frugiperda</i> ovarian cells compared their ATP-dependent properties vanadate-sensitive ATPase activities isolated membrane vesicles. Both actively transported leukotriene C<sub>4</sub> and<i>N</i>-ethylmaleimide glutathione (NEM-GS), although relative affinity for these substrates was found to be...
The human MDR3 gene is a member of the multidrug resistance (MDR) family. P-glycoprotein transmembrane protein that translocates phosphatidylcholine. MDR1 related transports cytotoxic drugs. Its overexpression can make cells resistant to variety Attempts show cause MDR have been unsuccessful thus far. Here, we report an increased directional transport several substrates, such as digoxin, paclitaxel, and vinblastine, through polarized monolayers MDR3-transfected cells. Transport other good...
Mutations in the <i>ABCC6</i> (MRP6) gene cause pseudoxanthoma elasticum (PXE), a rare heritable disorder resulting calcification of elastic fibers. In present study cDNA encoding full-length normal variant ABCC6 was amplified from human kidney library, and protein expressed Sf9 insect cells. isolated membranes ATP binding as well ATP-dependent active transport by demonstrated. We found that glutathione conjugates, including leukotriene C<sub>4</sub>...
Abstract Iressa (ZD1839, Gefitinib), used in clinics to treat non–small cell lung cancer patients, is a tyrosine kinase receptor inhibitor that leads specific decoupling of epidermal growth factor (EGFR) signaling. Recent data indicate especially effective tumors with certain EGFR mutations; however, subset these does not respond Iressa. In addition, populations have an elevated risk side effects during treatment. The human ABCG2 (BCRP/MXR/ABCP) transporter causes drug resistance by actively...
ABC multidrug transporters (MDR-ABC proteins) cause multiple drug resistance in cancer and may be involved the decreased anti-cancer efficiency modified pharmacological properties of novel specifically targeted agents. It has been documented that ABCB1 ABCG2 interact with several first-generation, small-molecule, tyrosine kinase inhibitors (TKIs), including Bcr-Abl fusion inhibitor imatinib, used for treatment chronic myeloid leukaemia. Here, we have investigated specific interaction these...
The membrane topology of the human multidrug resistance-associated protein (MRP) was examined by flow cytometry phenotyping, immunoblotting, and limited proteolysis in drug-resistant baculovirus-infected insect cells, expressing either glycosylated or underglycosylated forms this protein. Inhibition N-linked glycosylation cells tunicamycin did not inhibit transport function antibody recognition MRP, although its apparent molecular mass reduced from 180 kDa to 150 kDa. Extracellular addition...